kaolinite and Disease-Models--Animal

Topics: Animals; Anti-Inflammatory Agents; Bradykinin; Carrageenan; Cell Migration Inhibition; Dextrans; Disease Models, Animal; Drug Evaluation, Preclinical; Edema; Foot; Formaldehyde; Guinea Pigs; Histamine; Inflammation; Kaolin; Ovalbumin; p-Methoxy-N-methylphenethylamine; Povidone; Rabbits; Rats; Saccharomyces cerevisiae; Serotonin; Species Specificity

Topics: Angiotensin II; Animals; Aorta; Autonomic Nervous System; Blood Pressure; Brachiocephalic Trunk; Carotid Arteries; Catecholamines; Cats; Cerebral Ventricles; Disease Models, Animal; Dogs; Haplorhini; Hemodynamics; Hot Temperature; Hypertension; Kaolin; Methods; Rabbits; Rats; Subclavian Artery; Sympathectomy; Vascular Diseases

Flunixin is marketed in several countries for analgesia in adult swine but little is known about its efficacy in piglets. Thirty-two piglets (6-8 days old) were randomized to receive placebo saline (n = 11, group CONTROL) or flunixin meglumine intravenously at 2.2 (n = 11, group MEDIUM) or 4.4 (n = 10, group HIGH) mg/kg, 10 hr after subcutaneous injection of kaolin in the left metacarpal area. A hand-held algometer was used to determine each piglet's mechanical nociceptive threshold (MNT) from both front feet up to 50 hr after treatment (cut-off value of 24.5 newton). Serial venous blood samples were obtained to quantify flunixin in plasma using LC-MS/MS. A PKPD model describing the effect of flunixin on the mechanical nociceptive threshold was obtained based on an inhibitory indirect response model. A two-compartmental PK model was used. A significant effect of flunixin was observed for both doses compared to control group, with 4.4 mg/kg showing the most relevant (6-10 newton) and long-lasting effect (34 hr). The median IC50 was 6.78 and 2.63 mg/ml in groups MEDIUM and HIGH, respectively. The ED50 in this model was 6.6 mg/kg. Flunixin exhibited marked antinociceptive effect on kaolin-induced inflammatory hyperalgesia in piglets.

Topics: Analgesics; Animals; Animals, Newborn; Anti-Inflammatory Agents; Clonixin; Disease Models, Animal; Dose-Response Relationship, Drug; Inflammation; Injections, Intravenous; Kaolin; Pain Measurement; Swine

The aims of the study were to 1) determine the effectiveness of QuikClot Combat Gauze (QCG); 2) determine the arterial blood pressure at which rebleeding occurs; 3) determine how much intravenous fluid could be administered before hemorrhage reoccurred, and 4) determine the number extremity movement on rebleeding when QCG was used.. This was a prospective, randomized, experimental study.. Adult Yorkshire pigs were randomly assigned to two groups QCG (n = 10) or control (n = 10).. After the swine were anesthetized, the investigators transected the femoral artery and vein. After 1 minute of uncontrolled bleeding, QCG was placed in the wound followed by standard wound packing. The control group underwent the same procedures without QCG. After 5 minutes of firm, manual pressure, a pressure dressing was applied. Following 30 minutes, the dressings were removed and blood loss was calculated. If hemostasis occurred, phenylephrine was administered until there was rebleeding. If no bleeding, up to 5 L of IV crystalloid was administered until there was hemorrhage. If no bleeding, the extremity on the side of the hemorrhage was moved through flexion, extension, abduction, and adduction 10 times or until rebleeding occurred.. QCG compared to a control was more effective in controlling hemorrhage, withstanding increases in systolic blood pressure, more latitude in resuscitation fluid, and movement (p < 0.05).

Topics: Animals; Bandages; Disease Models, Animal; Femoral Artery; Hemorrhage; Hemostatics; Kaolin; Prospective Studies; Swine

Ventriculomegaly induced by the abnormal accumulation of cerebrospinal fluid (CSF) leads to hydrocephalus, which is accompanied by neuroinflammation and mitochondrial oxidative stress. The mitochondrial stress activates mitochondrial unfolded protein response (UPRmt), which is essential for mitochondrial protein homeostasis. However, the association of inflammatory response and UPRmt in the pathogenesis of hydrocephalus is still unclear. To assess their relevance in the pathogenesis of hydrocephalus, we established a kaolin-induced hydrocephalus model in 8-week-old male C57BL/6J mice and evaluated it over time. We found that kaolin-injected mice showed prominent ventricular dilation, motor behavior defects at the 3-day, followed by the activation of microglia and UPRmt in the motor cortex at the 5-day. In addition, PARP-1/NF-κB signaling and apoptotic cell death appeared at the 5-day. Taken together, our findings demonstrate that activation of microglia and UPRmt occurs after hydrocephalic ventricular expansion and behavioral abnormalities which could be lead to apoptotic neuronal cell death, providing a new perspective on the pathogenic mechanism of hydrocephalus. [BMB Reports 2022; 55(4): 181-186].

Topics: Animals; Disease Models, Animal; Hydrocephalus; Kaolin; Male; Mice; Mice, Inbred C57BL; Microglia; Unfolded Protein Response

Popularly known as "escoba" (broom) or "escobilla china" (Chinese brush), Baccharis conferta Kunth (Asteraceae), is a plant widely used in Mexican folk medicine for alleviating muscular and rheumatic pain. A recent study described that dichloromethane extract as well as fractions and isolated compounds, possess anti-inflammatory activity in TPA-induced acute edema.. Based on the popular medicinal uses of B. conferta as well as previous studies on its anti-inflammatory activity, the aim of this research was to evaluate the anti-arthritic and anti-inflammatory effects of dichloromethane extract, fractions, and compounds from B. conferta in a monoarthritis model induced with kaolin/carrageenan (K/C).. Aerial parts of B. conferta were collected, dried, and macerated with dichloromethane. The dichloromethane extract (BcD) was separated by open column chromatography to obtain the BcD2 fraction where the diterpene kingidiol (KIN) was isolated and from the BcD3 fraction the flavonoid cirsimaritin (CIR), which are the most active compounds in the TPA model. In addition, the flavonoids acacetin, pectolinaringenin and 6-methoxykaempferide were identified and isolated from the BcD2 fraction. The content of the main compounds was estimated in BcD, BcD2 and BcD3. The anti-arthritic and anti-inflammatory effects of B. conferta were investigated by evaluating ankle joint inflammation, hyperalgesia using the hot plate test, and pro- and anti-inflammatory cytokine levels in the synovial capsule as well as histological changes in ankle joint tissue in a monoarthritis model induced with K/C in Balb/c mice.. Oral administration of BcD2 fraction (25 mg/kg) and KIN (10 mg/kg) reduced the ankle thickness induced by K/C and decreased the levels of TNF-α, IL-1β, IL-6 and IL-17, while BcD2 increased IL-10. In addition, BcD2 and KIN showed significant edema attenuation of the synovial membrane and decreased inflammatory infiltration and cartilage erosion compared to the VEH group. Finally, BcD (50 mg/kg), KIN (10 mg/kg) and CIR (5 mg/kg) decreased hyperalgesia.. B. conferta constitutes a therapeutic or preventive candidate for osteoarthritis, because of decreased articular inflammation and pain accompanied with the modulation of cytokine concentrations, which confirms the anti-arthritic and anti-inflammatory activities of B. conferta and support its popular use.

Topics: Animals; Anti-Inflammatory Agents; Arthritis, Experimental; Baccharis; Carrageenan; Disease Models, Animal; Hyperalgesia; Inflammation; Kaolin; Male; Medicine, Traditional; Mice; Mice, Inbred BALB C; Plant Extracts

Death from acute hemorrhage is a major problem in military conflicts, traffic accidents, and surgical procedures, et al. Achieving rapid effective hemostasis for pre-hospital care is essential to save lives in massive bleeding. An ideal hemostasis material should have those features such as safe, efficient, convenient, economical, which remains challenging and most of them cannot be achieved at the same time. In this work, we report a rapid effective nanoclay-based hemostatic membranes with nanoclay particles incorporate into polyvinylpyrrolidone (PVP) electrospun fibers. The nanoclay electrospun membrane (NEM) with 60 wt% kaolinite (KEM1.5) shows better and faster hemostatic performance in vitro and in vivo with good biocompatibility compared with most other NEMs and clay-based hemostats, benefiting from its enriched hemostatic functional sites, robust fluffy framework, and hydrophilic surface. The robust hemostatic bandages based on nanoclay electrospun membrane is an effective candidate hemostat in practical application.

Topics: Animals; Bandages; Clay; Disease Models, Animal; Hemorrhage; Hemostasis; Hemostatics; Humans; Kaolin; Liver; Male; Nanostructures; Povidone; Rats; Rats, Sprague-Dawley; Spleen; Surgical Wound

Many animal models have been used to study the pathophysiology of hydrocephalus; most of these have been rodent models whose lissencephalic cerebral cortex may not respond to ventriculomegaly in the same way as gyrencephalic species and whose size is not amenable to evaluation of clinically relevant neurosurgical treatments. Fewer models of hydrocephalus in gyrencephalic species have been used; thus, we have expanded upon a porcine model of hydrocephalus in juvenile pigs and used it to explore surgical treatment methods.. Acquired hydrocephalus was induced in 33-41-day old pigs by percutaneous intracisternal injections of kaolin (n = 17). Controls consisted of sham saline-injected (n = 6) and intact (n = 4) animals. Magnetic resonance imaging (MRI) was employed to evaluate ventriculomegaly at 11-42 days post-kaolin and to plan the surgical implantation of ventriculoperitoneal shunts at 14-38-days post-kaolin. Behavioral and neurological status were assessed.. Bilateral ventriculomegaly occurred post-induction in all regions of the cerebral ventricles, with prominent CSF flow voids in the third ventricle, foramina of Monro, and cerebral aqueduct. Kaolin deposits formed a solid cast in the basal cisterns but the cisterna magna was patent. In 17 untreated hydrocephalic animals. Mean total ventricular volume was 8898 ± 5917 SD mm. Kaolin induction of acquired hydrocephalus in juvenile pigs produced an in vivo model that is highly translational, allowing systematic studies of the pathophysiology and clinical treatment of hydrocephalus.

Topics: Age Factors; Animals; Disease Models, Animal; Hydrocephalus; Kaolin; Magnetic Resonance Imaging; Swine; Ventriculoperitoneal Shunt

Cerebellar abnormalities are commonly associated with hydrocephalus. However, the effect of hydrocephalus on the otherwise normal cerebellum has been largely neglected. This study assesses the morphological changes in the Purkinje cells in relation to cerebellar dysfunction observed in juvenile hydrocephalic rats. Fifty-five three-week old albino Wistar rats were used, hydrocephalus was induced by intracisternal injection of kaolin (n = 35) and others served as controls (n = 20). Body weight measurements, hanging wire, negative geotaxis, and open field tests were carried out at the onset and then weekly for 4 weeks, rats were killed, and their cerebella processed for Hematoxylin and Eosin, Cresyl violet and Golgi staining. Qualitative and quantitative studies were carried out; quantitative data were analyzed using two-way ANOVA and independent T tests at p < 0.05. Hydrocephalic rats weighed less than controls (p = 0.0247) but their cerebellar weights were comparable. The hydrocephalic rats had a consistently shorter latency to fall in the hanging wire test (F(4,112) = 18.63; p < 0.0001), longer latency to turn in the negative geotaxis test (F(4,112) = 22.2; p < 0.0001), and decreased horizontal (F(4,112) = 4.172, p = 0.0035) and vertical movements (F(4,112) = 4.397; p = 0.0024) in the open field test than controls throughout the 4 weeks post-induction. Cellular compression in the granular layer, swelling of Purkinje cells with vacuolations, reduced dendritic arborization and increased number of pyknotic Purkinje cells were observed in hydrocephalic rats. Hydrocephalus caused functional and morphological changes in the cerebellar cortex. Purkinje cell loss, a major pathological feature of hydrocephalus, may be responsible for some of the motor deficits observed in this condition.

Topics: Animals; Cerebellum; Disease Models, Animal; Hydrocephalus; Kaolin; Movement; Psychomotor Performance; Purkinje Cells; Rats, Wistar

Adhesions are often considered to be an inevitable consequence of abdominal and pelvic surgery, jeopardizing the medium and long-term success of these procedures. Numerous strategies have been tested to reduce adhesion formation, however, to date, no surgical or medical therapeutic approaches have been successful in its prevention. This study demonstrates the safety and efficacy of Chitogel with Deferiprone and/or antibacterial Gallium Protoporphyrin in different concentrations in preventing adhesion formation after abdominal surgery.. 112 adult (8-10 week old) male Wistar albino rats were subjected to midline laparotomy and caecal abrasion, with 48 rats having an additional enterotomy and suturing. Kaolin (0.005g/ml) was applied to further accelerate adhesion formation. The abrasion model rats were randomized to receive saline, Chitogel, or Chitogel plus Deferiprone (5, 10 or 20 mM), together with Gallium Protoporphyrin (250μg/mL). The abrasion with enterotomy rats were randomised to receive saline, Chitogel or Chitogel with Deferiprone (1 or 5 mM). At day 21, rats were euthanised, and adhesions graded macroscopically and microscopically; the tensile strength of the repaired caecum was determined by an investigator blinded to the treatment groups.. Chitogel with Deferiprone 5 mM significantly reduced adhesion formation (p<0.01) when pathologically assessed in a rat abrasion model. Chitogel with Deferiprone 5 mM and 1 mM also significantly reduced adhesions (p<0.05) after abrasion with enterotomy. Def-Chitogel 1mM treatment did not weaken the enterotomy site with treated sites having significantly better tensile strength compared to control saline treated enterotomy rats.. Chitogel with Deferiprone 1 mM constitutes an effective preventative anti-adhesion barrier after abdominal surgery in a rat model. Moreover, this therapeutic combination of agents is safe and does not weaken the healing of the sutured enterotomy site.

Topics: Abdomen; Animals; Cecum; Chitosan; Deferiprone; Disease Models, Animal; Enterostomy; Gels; Kaolin; Protoporphyrins; Rats; Rats, Wistar; Tensile Strength; Tissue Adhesions

Necroptosis is widespread in neurodegenerative diseases. Here, we examined necroptosis in the hippocampus and cortex after hydrocephalus and found that a necroptosis pathway inhibitor alleviates necroptosis and provides neuroprotective effects.. Hydrocephalus was induced in C57BL/6 mice by kaolin. Haematoxylin and eosin (HE), Nissl, PI and Fluoro-Jade B (FJB) staining were used for general observations. Phosphorylated receptor-interacting protein kinase 3 (p-RIP3) and phosphorylated mixed lineage kinase domain-like (p-MLKL) were measured by Western blotting and immunohistochemistry. Scanning electron microscopy (SEM) was used to observe ependymal cilia. Magnetic resonance imaging (MRI) and the Morris water maze (MWM) test were used to assess neurobehavioral changes. Immunofluorescence was used to detect microglial and astrocyte activation. Inflammatory cytokines were measured by Western blotting and RT-PCR.. Obvious pathological changes appeared in the hippocampus and cortex after hydrocephalus, and expression of the necroptosis markers p-RIP3, p-MLKL and inflammatory cytokines increased. Necrostatin-1 (Nec-1) and GSK872 reduced necrotic cell death, attenuated p-RIP3 and p-MLKL levels, slightly improved neurobehaviours and inhibited microglial and astrocyte activation and inflammation.. RIP1/RIP3/MLKL mediates necroptosis in the cortex and hippocampus in a hydrocephalus mouse model, and Nec-1 and GSK872 have some neuroprotective effects.

Topics: Animals; Cytokines; Disease Models, Animal; GTPase-Activating Proteins; Hydrocephalus; Imidazoles; Indoles; Inflammation; Kaolin; Mice; Mice, Inbred C57BL; Necroptosis; Neuroprotective Agents; Phosphorylation; Protein Kinases; Receptor-Interacting Protein Serine-Threonine Kinases; Signal Transduction

Oenothera rosea (Onagraceae), commonly known as "hierba del golpe" in Mexico, is an herbaceous plant widely used in Mexican traditional medicine for the treatment of pain and inflammation.. The aim of this study was to assess the effect of extracts and compounds isolated from O. rosea in kaolin-carrageenan induced arthritis.. Hydroalcoholic extract from aerial parts of O. rosea was obtained and chemically separated in order to obtain OrEA and isolated compounds using column chromatography, HPLC, UPLC and NMR analysis. O. rosea extract and derivatives were tested on the kaolin/carrageenan (K/C) induced arthritis model on ICR mice. Knee inflammation and paw withdrawal threshold were assessed following intraarticular administration of kaolin and carrageenan (4% and 2%, respectively) and subsequent oral administration of O. rosea. TNF-α, IL-1β, IL-6 and IL-10 levels from synovial capsule were measured using ELISA kits. NF-κB activity was also measured using the RAWBlue™ cell line. Finally, spleen and lungs were dissected to investigate body index.. Oral administration of the O. rosea ethyl acetate fraction (25, 50 and 100 mg/kg) and isolated compounds (2 mg/kg) reduced the edema induced by kaolin/carrageenan, similar to the effect of methotrexate (1 mg/kg). Hyperalgesia but not allodynia was observed during this experiment. O. rosea derivatives reduced this behavior. The quantification of cytokines showed a reduction in TNF-α, IL-1β and IL-6, as well as an increase of IL-10. NF-κB production was also reduced by administering O. rosea derivatives. Chemical analysis of O. rosea derivatives showed that the major compounds present in the ethyl acetate fraction were phenolic compounds. Gallic acid, quercetin glucoside and quercetin rhamnoside were separated and identified by UPLC-UV-MS, and myricetin glycoside and tamarixetin glucoside using. O. rosea produces different phenolic compounds capable of reducing the inflammation and secondary mechanical hyperalgesia produced by K/C administration. They also reduced proinflammatory cytokines and increased anti-inflammatory cytokines. Finally, NF-κB modulation was reduced by the administration of O. rosea. Therefore, O. rosea could be considered of interest in inflammatory and painful diseases.

Topics: Analgesics; Animals; Anti-Inflammatory Agents; Arthritis; Carrageenan; Cell Line; Cytokines; Disease Models, Animal; Female; Hyperalgesia; Kaolin; Mice, Inbred ICR; NF-kappa B; Oenothera; Phenols; Phytochemicals; Plant Components, Aerial; Plant Extracts; Synovial Membrane

Urokinase-type plasminogen activator (uPA) was demonstrated to alleviate kaolin-induced communicating hydrocephalus via inhibiting subarachnoid space fibrosis, but the exact mechanism remains elusive. Thus, this study was designed to investigate if hepatocyte growth factor (HGF), which plays a vital role in uPA-triggered inhibiting of fibrosis in multiple systems, is involved in this process in hydrocephalus. There were 2 parts in this study. First, hydrocephalus was induced in rats by basal cistern injection of kaolin. Then rats were treated with saline or uPA and brain tissue and CSF were collected for Western blot and enzyme-linked immuno sorbent assay (ELISA) four days later. Second, kaolin-induced hydrocephalus rats were treated with saline, uPA, uPA + PHA665752 (antagonist of HGF) or PHA665752. Some animals received MRI four weeks later and brains were used for immunofluorescence. The others were euthanized four days later for ELISA. Both levels of total and activated HGF in the CSF was increased after uPA injections, but related mRNA expression of HGF showed no statistical significance when compared with the control group. Further, the effects of uPA that alleviating ventricular enlargement, subarachnoid fibrosis and reactive astrocytosis were partially reversed by PHA665752. Moreover, PHA665752 partially abolished uPA-induced reduction of transforming growth factor- β1(TGF- β1) level in CSF. Our data suggest that uPA effectively inhibited subarachnoid fibrosis and restricted the development of communicating hydrocephalus in rats in part by promoting HGF release and activation, which may further regulate the TGF-β1 expression in CSF.

Topics: Animals; Brain; Disease Models, Animal; Hepatocyte Growth Factor; Hydrocephalus; Kaolin; Male; Rats, Sprague-Dawley; Transforming Growth Factor beta1; Urokinase-Type Plasminogen Activator

In hydrocephalus, the progressive accumulation of cerebrospinal fluid (CSF) causes dilatation of the lateral ventricles affecting the third ventricle and diencephalic structures such as the hypothalamus. These structures play a key role in the regulation of several neurovegetative functions by the production of the hormones. Since endocrine disturbances are commonly observed in hydrocephalic children, we investigated the impact of progressive ventricular dilation on the hypothalamus of infant rats submitted to kaolin-induced hydrocephalus. Seven-day-old infant rats were submitted to hydrocephalus induction by kaolin 20% injection method. After 14 days, the animals were decapitated and brain was collected to analyze mitochondrial function, neuronal activity by acetylcholinesterase (AChE) enzyme, oxidative damage, glial activation, and, neurotransmission-related proteins and anti-apoptotic processes in the hypothalamus. The hydrocephalic animals showed reduction in respiratory rates in the States of phosphorylation (P < 0.01) and non-phosphorylation (P < 0.05); increase in AChE activity in both the cytosol (P < 0.05) and the membrane (P < 0.01); decrease in synaptophysin (P < 0.05) and Bcl-2 (P < 0.05) contents and; increase in protein carbonyl (P < 0.01), GFAP (P < 0.01) and Iba-1 (P < 0.05) levels. The results demonstrate that ventricular dilation causes hypothalamic damage characterized by cholinergic dysfunction and suggests further investigation of the synthesis and secretion of hormones to generate new approaches and to assist in the treatment of hydrocephalic patients with hormonal alterations.

Topics: Acetylcholinesterase; Animals; Animals, Newborn; Brain; Cerebral Ventricles; Disease Models, Animal; Hydrocephalus; Hypothalamus; Kaolin; Lateral Ventricles; Male; Neurons; Rats; Rats, Wistar

To demonstrate progression of acute and chronic endocrinopathies in a kaolin-induced hydrocephalus model using light microscopy.. Adult male Sprague-Dawley rats (n = 48) were divided into six groups. Hydrocephalus was induced by intracisternal injection of kaolin solution in the acute and chronic kaolin groups, whereas an identical volume of sterile saline was injected into the sham groups.. Somatotropic cell concentrations were lower in the kaolin groups compared with their controls, but there was no difference in somatotropic cell concentration between the acute and chronic kaolin groups. Corticotropic cell concentrations were higher in the acute kaolin and sham groups compared with acute controls. Thyrotropic cell numbers were higher in the acute sham and kaolin groups compared with their controls, and although thyrotropic cell concentations were higher in the acute kaolin group than the acute sham group. No differences were observed between the acute and chronic controls and sham and kaolin groups regarding mammotropicand gonadototropic cell concentations.. Somatotropic cells are most affected by hydrocephalus that causes pituitary dysfunction, and this effect was more prominent under acute and chronic phases.

Topics: Acute Disease; Animals; Chronic Disease; Disease Models, Animal; Hydrocephalus; Kaolin; Male; Microscopy; Pituitary Diseases; Rats; Rats, Sprague-Dawley

The pathophysiology of hydrocephalus induced brain damage remains unclear. Long non-coding RNAs (lncRNAs) have been demonstrated to be implicated in many central nervous system diseases. However, the roles of lncRNAs in hydrocephalus injury are poorly understood.. The present study depicted the expression profiles of lncRNAs and messenger RNAs (mRNAs) in C57BL/6 mice with kaolin-induced hydrocephalus and saline controls using high-throughput RNA sequencing. Afterward, Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to identify potential targets that correlated with hydrocephalus. In addition, co-expression networks and cis- and trans-regulation were predicted using bioinformatics methods. Finally, representative lncRNAs and mRNAs were further validation using quantitative real-time polymerase chain reaction.. A total of 1575 lncRNAs and 1168 mRNAs were differentially expressed (DE) in hydrocephalus. GO and KEGG analyses indicated several immune and inflammatory response-associated pathways may be important in the hydrocephalus. Besides, functional enrichment analysis based on co-expression network showed several similar pathways, such as chemokine signaling pathway, phagosome, MAPK signaling pathway and complement and coagulation cascade. Cis-regulation prediction revealed 5 novel lncRNAs might regulate their nearby coding genes, and trans-regulation revealed several lncRNAs participate in pathways regulated by transcription factors, including BPTF, FOXM1, NR5A2, P2RX5, and NR6A1.. In conclusion, our results provide candidate genes involved in hydrocephalus and suggest a new perspective on the modulation of lncRNAs in hydrocephalus.

Topics: Animals; Computational Biology; Disease Models, Animal; Gene Expression Profiling; Gene Ontology; Genome; High-Throughput Nucleotide Sequencing; Hydrocephalus; Kaolin; Male; Mice; Mice, Inbred C57BL; Oligonucleotide Array Sequence Analysis; Real-Time Polymerase Chain Reaction; RNA, Long Noncoding; RNA, Messenger; Transcriptome

Idiopathic normal pressure hydrocephalus (iNPH) is a cause of dementia that can be reversed when treated timely with cerebrospinal fluid (CSF) diversion. Understanding CSF dynamics throughout the development of hydrocephalus is crucial to identify prognostic markers to estimate benefit/risk to shunts.. To explore the cerebral aqueduct CSF flow dynamics with phase-contrast magnetic resonance imaging (MRI) in a novel rodent model of adult chronic communicating hydrocephalus.. Kaolin was injected into the subarachnoid space at the convexities in Sprague-Dawley adult rats. 11.7-T Bruker MRI was used to acquire T2-weighted images for anatomic identification and phase-contrast MRI at the cerebral aqueduct. Aqueductal stroke volume (ASV) results were compared with the ventricular volume (VV) at 15, 60, 90, and 120 days.. Significant ventricular enlargement was found in kaolin-injected animals at all times (P < 0.001). ASV differed between cases and controls/shams at every time point (P = 0.004, 0.001, 0.001, and <0.001 at 15, 60, 90, and 120 days, respectively). After correlation between the ASV and the VV, there was a significant correlation at 15 (P = 0.015), 60 (P = 0.001), 90 (P < 0.001), and 120 days. Moreover, there was a significant positive correlation between the VV expansion and the aqueductal CSF stroke between 15 and 60 days.. An initial active phase of rapid ventricular enlargement shows a strong correlation between the expansion of the VV and the increment in the ASV during the first 60 days, followed by a second phase with less ventricular enlargement and heterogeneous behavior in the ASV. Further correlation with complementary data from intracranial pressure and histologic/microstructural brain parenchyma assessments are needed to better understand the ASV variations after 60 days.

Topics: Animals; Cerebral Aqueduct; Cerebrospinal Fluid; Contrast Media; Disease Models, Animal; Disease Progression; Hydrocephalus; Hydrodynamics; Kaolin; Magnetic Resonance Imaging; Organ Size; Rats, Sprague-Dawley

Topics: Animals; Astrocytes; Cerebral Ventricles; Cerebrospinal Fluid; Contrast Media; Dextrans; Disease Models, Animal; Endothelial Cells; Female; Humans; Hydrocephalus; Immunohistochemistry; Kaolin; Magnetic Resonance Imaging; Neurons; Parenchymal Tissue; Random Allocation; Rats, Sprague-Dawley

Memantine is a selective, non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist that has previously been shown to have neuroprotective qualities in some animal models of neurologic disease. We hypothesized that memantine therapy would improve behavioral, neuropathological, and/or biochemical outcomes in juvenile rats with kaolin-induced hydrocephalus. Three-week old rats received an injection of kaolin (aluminum silicate) into the cisterna magna. Magnetic resonance imaging was performed one week later to assess ventricle size and stratify rats to three treatment groups. Rats were blindly treated daily for three weeks with saline or 10 or 30 mg/kg/day memantine. Behavior measures were performed weekly. Histologic and biochemical evaluations were performed at termination. Hydrocephalic rats showed no differences in weight among treatment groups. Memantine treatment stabilized ventricular enlargement in both low and high dose groups. The high dose group exhibited increased motor activity in open field chambers compared to the vehicle-treated group. However, there were no significant differences between the three hydrocephalic treatment groups for other behavioral tasks. Ventriculomegaly was associated with periventricular white matter damage. Glial fibrillary acidic protein (GFAP) content was higher in the low dose memantine group compared to vehicle-treated group, but there were no differences in GFAP-immunoreactive astrocytes or Iba-1- immunoreactive microglia between groups. Memantine therapy stabilized ventricular expansion and improved some behavioral measures but did not reduce brain tissue changes in juvenile rats with kaolin-induced hydrocephalus.

Topics: Animals; Body Weight; Cerebral Ventricles; Disease Models, Animal; Excitatory Amino Acid Antagonists; Female; Hydrocephalus; Kaolin; Male; Memantine; Motor Activity; Neuroprotective Agents; Rats, Long-Evans; Receptors, N-Methyl-D-Aspartate; Single-Blind Method; White Matter

Topics: Animals; Animals, Newborn; Brain; Calcium Channel Blockers; Disease Models, Animal; Dose-Response Relationship, Drug; Female; Ferrets; Hydrocephalus; Kaolin; Male; Nimodipine; Treatment Failure

Hydrocephalus is defined as an incapacitating neurological disorder characterized by ventricular enlargement in children, but the effects of melatonin on this hydrocephalus have not yet been fully elucidated. In the present experiment, we attempted to investigate the effects of exogenous melatonin administration on hydrocephalus-induced hippocampal changes in infantile rats.. In this study, we randomly divided 45 Swiss albino rats aged 2 weeks into 3 groups: group I, the control group received a sham injection with needle insertion only; groups II and III were given kaolin injections before treatment - group II, the hydrocephalus group, was treated with an isotonic NaCl solution, and group III, the hydrocephalus plus melatonin group, was treated with 0.5 mg/100 g body weight of exogenous melatonin. Both immunohistochemical and histological analyses were performed after hydrocephalus induction and melatonin administration. Immunohistochemical staining consisted anti-glial fibrillary acidic protein staining. The TUNEL technique was used for defining quantitate apoptosis.. Melatonin administration significantly attenuated chronic hydrocephalus-induced histopathological changes in the hippocampal subregions of infantile rats. Compared to hydrocephalic rats treated with saline solution, melatonin significantly decreased the number of apoptotic cells and pyknotic index values of each hippocampal subregion after the kaolin-induced hydrocephalus (p < 0.001).. The present results demonstrate that the chronic hydrocephalus-induced histopathological changes in the hippocampus were partially reversible with melatonin treatment, suggesting its neuroprotective effects in infantile rats. However, these findings need to be confirmed by further experimental studies and clinical trials.

Topics: Animals; Animals, Newborn; Disease Models, Animal; Glial Fibrillary Acidic Protein; Hippocampus; Humans; Hydrocephalus; Immunohistochemistry; Kaolin; Melatonin; Neuroprotective Agents; Rats

Motion sickness (MS) is an acute disorder that occurs in healthy individuals worldwide regardless of gender, age, or ethnicity. Our study used a mouse model to rule out the effects of any psychological factors related to MS and EA. Subjects were randomly separated into four groups, namely the control group (Con), motion sickness inducing group (MS), mentioning sickness inducing with electroacupuncture treatment group (EA) and motion sickness inducing only in TRPV1 knockout mice group (TRPV1

Topics: Animals; Brain Stem; Disease Models, Animal; Electroacupuncture; Extracellular Signal-Regulated MAP Kinases; Gene Deletion; Hypothalamus; Kaolin; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Motion Sickness; NF-kappa B; Signal Transduction; Thalamus; TRPV Cation Channels

The pathophysiology of normal-pressure hydrocephalus and the correlation with its symptomatology is not well understood.. To monitor and evaluate the enlargement patterns of the ventricular system for each ventricle and its correlation with the presenting symptoms.. Bilateral kaolin injection into the subarachnoid space overlying the cranial convexities was done in 18 adult rats. Magnetic resonance imaging was performed on an 11.7-T scanner 15, 60, 90, and 120 days after injection. Volumes of the ventricular system were measured for each ventricle and correlated with biweekly behavioral findings.. There was a progressive increase in the ventricular volume for the lateral ventricles since day 15 in the kaolin-injected animals. There was a nonsignificant trend in volume growth for the third ventricle, but its enlargement was synchronous with the lateral ventricles. No significant change for the fourth ventricle. No symptoms were detected in the first 60 days. Association was found between the ventricular volume and locomotor changes. In addition, the odds of locomotor symptoms increased by 3% for every additional cubic millimeter of volume in the left (P < 0.001) and right (P = 0.023) ventricles, and for the total magnetic resonance imaging volume by 1% (P = 0.013).. Expansion of the lateral ventricles maintained similar proportions over time, accompanied by a synchronous third ventricular expansion with less proportion and a nonsignificant fourth enlargement. Lateral ventricles enlarged most in those animals that were to develop late locomotor deterioration. Further research using this animal model combined with different radiologic imaging techniques, such as diffusion tensor imaging and perfusion studies, is recommended.

Topics: Animals; Cerebral Ventricles; Disease Models, Animal; Disease Progression; Female; Hydrocephalus; Kaolin; Magnetic Resonance Imaging; Organ Size; Rats, Sprague-Dawley

Retrohepatic inferior vena cava (RIVC) injuries are often lethal due to challenges in obtaining hemorrhage control. We hypothesized that packing with a new kaolin-based hemostatic dressing (Control+; Z-Medica, Wallingford, CT) would improve hemorrhage control from a penetrating RIVC injury compared with packing with standard laparotomy sponges alone.. Twelve male Yorkshire pigs received a 25% exchange transfusion of blood for refrigerated normal saline to induce a hypothermic coagulopathy. A laparotomy was performed and a standardized 1.5 cm injury to the RIVC was created which was followed by temporary abdominal closure and a period of uncontrolled hemorrhage. When the mean arterial pressure reached 70% of baseline, demonstrating hemorrhagic shock, the abdomen was re-entered, and the injury was treated with perihepatic packing using standard laparotomy sponges (L; n = 6) or a new kaolin-based hemostatic dressing (K; n = 6). Animals were then resuscitated for 6 hours with crystalloid solution. The two groups were compared using the Wilcoxon rank sum test and Fisher exact test. A p value of 0.05 or less was considered statistically significant.. There was no difference in the animal's temperature, heart rate, mean arterial pressure, cardiac output, and blood loss at baseline or before packing was performed (all p > 0.05). In the laparotomy sponge group, five of six pigs survived the entire study period, whereas all six pigs treated with kaolin-based D2 hemostatic dressings survived. Importantly, there was significantly less blood loss after packing with the new hemostatic kaolin-based dressing compared with packing with laparotomy sponge (651 ± 180 mL vs. 1073 ± 342 mL; p ≤ 0.05).. These results demonstrate that the use of this new hemostatic kaolin-based dressing improved hemorrhage control and significantly decreased blood loss in this penetrating RIVC model.. This is basic science research based on a large animal model, level V.

Topics: Animals; Disease Models, Animal; Hemorrhage; Hemostatics; Kaolin; Male; Swine; Vascular System Injuries; Vena Cava, Inferior

Hydrocephalus is a developmental disorder causing abnormally collected cerebrospinal fluid within the cerebral ventricles. It leads to bigger skulls and many dysfunctions related to the nervous system. Here, we addressed whether exogenous melatonin administration could reverse the clinical features of kaolin-induced hydrocephalus in infantile rats. A controlled double-blinded study was conducted in 2-week-old 45 Wistar albino rats, which were divided into three groups: Group A, the control group, received intracisternal sham injection with solely the needle insertion; group B, the hydrocephalus group, was treated with isotonic NaCl after kaolin injection; and group C, the hydrocephalus + melatonin group, was given i.p. exogenous melatonin at a dose of 0.5 mg/100 g body weight after kaolin injection. Histological and immunohistochemical analyses were performed after the induction of hydrocephalus and melatonin administration. Glial fibrillary acidic protein was stained by immunohistochemical method. TUNEL method was used to define and quantitate apoptosis in the cerebellar tissues. Statistical analysis was performed by nonparametric Kruskal-Wallis H test, and once significance was determined among means, post hoc pairwise comparisons were carried out using Mann-Whitney U test. We found that melatonin administration significantly ameliorated ratio of substantia grisea area/substantia alba area in the cerebellum of infantile rats. Histologically, there was a significant reduction in the number of cerebellar apoptotic cells after the hydrocephalus induced by kaolin (P < 0.05). Our results clearly revealed that the histopathological changes in the cerebellum were reversed by systemic melatonin administration in infantile rats with kaolin-induced hydrocephalus. Nevertheless, further studies are needed to suggest melatonin as a candidate protective drug in children with hydrocephalus.

Topics: Animals; Animals, Newborn; Apoptosis; Cerebellum; Disease Models, Animal; Double-Blind Method; Glial Fibrillary Acidic Protein; Hydrocephalus; Immunohistochemistry; In Situ Nick-End Labeling; Kaolin; Melatonin; Neuroprotective Agents; Rats, Wistar

Patients with diabetes mellitus have an increased cardiovascular risk due to the abnormality of hemostatic system components. Therefore, hemostasis is an important concept when considering that diabetics are under risk due to potential bleeding complications during surgical operation. The aim of our study was to examine the efficiency of a fabricated nano/microbilayer hemostatic dressing for bleeding control in diabetic patients. For this purpose, we prepared a nano/microbilayer hemostatic dressing that has a porous sublayer, including chitosan (CTS), bacterial cellulose (BC) as basement and active agents in coagulation cascade, such as vitamin K (Vit K), protamine sulfate (PS), and kaolin (Kao) as a filler and an upper layer consisting of silk fibroin (SF) or SF/phosphatidylcholine (PC) blend to achieve complete hemostasis in diabetic rats. Coagulative performances of the prepared hemostatic dressings were examined by the determination of bleeding time, blood loss, and mortality rate through diabetic rat femoral artery injury model. The percent of diabetic rat blood absorption was found to be 247 ± 5% for gauze as opposed to 2214 ± 56% for SF-coated PS/BC/CTS. Vit K-reinforced within 138 s and SF-coated BC/CTS hemostatic dressings within 144 s showed a rapid coagulation time. In vivo coagulation studies demonstrated that hemostatic agent-reinforced BC/CTS hemostatic dressing, especially PS/BC/CTS showed a significant hemostatic plug formation. This study suggests that the high positive charge and porosity give to these hemostatic agents reinforced hemostatic dressings the ability to rapidly swell and to promote the accumulation of red blood cells and platelets through electrostatic interactions. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1573-1585, 2017.

Topics: Animals; Bandages; Cellulose; Chitosan; Disease Models, Animal; Female; Femoral Artery; Fibroins; Hemorrhage; Hemostatics; Kaolin; Protamines; Rats; Rats, Sprague-Dawley

Hydrocephalus is a common neurological disorder in children characterized by abnormal dilation of cerebral ventricles as a result of the impairment of cerebrospinal fluid flow or absorption. Clinical presentation of hydrocephalus varies with chronicity and often shows cognitive dysfunction. Here we used a kaolin-induction method in rats and studied the effects of hydrocephalus on cerebral cortex and hippocampus, the two regions highly related to cognition. Hydrocephalus impaired rats' performance in Morris water maze task. Serial three-dimensional reconstruction from sections of the whole brain freshly froze in situ with skull shows that the volumes of both structures were reduced. Morphologically, pyramidal neurons of the somatosensory cortex and hippocampus appear to be distorted. Intracellular dye injection and subsequent three-dimensional reconstruction and analyses revealed that the dendritic arbors of layer III and V cortical pyramid neurons were reduced. The total dendritic length of CA1, but not CA3, pyramidal neurons was also reduced. Dendritic spine densities on both cortical and hippocampal pyramidal neurons were decreased, consistent with our concomitant findings that the expressions of both synaptophysin and postsynaptic density protein 95 were reduced. These cortical and hippocampal changes suggest reductions of excitatory connectivity, which could underlie the learning and memory deficits in hydrocephalus.

Topics: Animals; Antidiarrheals; Cerebral Cortex; Dendritic Spines; Disease Models, Animal; Disks Large Homolog 4 Protein; Hippocampus; Hydrocephalus; Kaolin; Maze Learning; Memory Disorders; Nerve Net; Neurons; Rats; Rats, Sprague-Dawley; Spatial Learning; Time Factors

We investigated the possible neuroprotective effects of the free radical scavenger edaravone in experimental hydrocephalus.. Seven-day-old Wistar rats were divided into three groups: control group (C), untreated hydrocephalic (H), and hydrocephalic treated with edaravone (EH). The H and EH groups were subjected to hydrocephalus induction by 20% kaolin intracisternal injection. The edaravone (20 mg/kg) was administered daily for 14 days from the induction of hydrocephalus. All animals were daily weighed and submitted to behavioral test and assessment by magnetic resonance imaging. After 14 days, the animals were sacrificed and the brain was removed for histological, immunohistochemical, and biochemical studies.. The gain weight was similar between groups from the ninth post-induction day. The open field test performance of EH group was better (p < 0.05) as compared to untreated hydrocephalic animals. Hydrocephalic animals (H and EH) showed ventricular ratio values were higher (p < 0.05), whereas magnetization transfer values were lower (p < 0.05), as compared to control animals. Astrocyte activity (glial fibrillary acidic protein) and apoptotic cells (caspase-3) of EH group were decreased on the corpus callosum (p > 0.01), germinal matrix (p > 0.05), and cerebral cortex (p > 0.05), as compared to H group.. We have demonstrated that administration of edaravone for 14 consecutive days after induction of hydrocephalus reduced astrocyte activity and that it has some beneficial effects over apoptotic cell death.

Topics: Animals; Antidiarrheals; Antipyrine; Apoptosis; Body Weight; Caspase 3; Disease Models, Animal; Edaravone; Exploratory Behavior; Free Radical Scavengers; Glial Fibrillary Acidic Protein; Gliosis; Hydrocephalus; In Situ Nick-End Labeling; Kaolin; Magnetic Resonance Imaging; Male; Neuroglia; Phosphopyruvate Hydratase; Rats; Rats, Wistar

Ghrelin can alleviate cancer chemotherapy-induced dyspepsia in rodents, though the neural mechanisms involved are not known. Therefore, ghrelin projections from the lateral hypothalamus (LH) and its involvement in the regulation of gastric motility in cisplatin-treated rats were investigated with a multi-disciplined approach. Retrograde tracing combined with fluoro-immunohistochemical staining were used to investigate ghrelin fiber projections arising from LH and projecting to nucleus tractus solitaries (NTS). Results revealed that ghrelin fibers originating in LH project to NTS. Expression of ghrelin and its receptor growth hormone secretagogue receptor (GHS-R1a) in LH and NTS were detected by Western Blot. 2days after cisplatin dosing, expression of ghrelin in LH decreased while GHS-R1a in both LH and NTS increased. In electrophysiological experiments, the effects of N-methyl-d-aspartate (NMDA) microinjection in LH on neuronal discharge of gastric distension-responsive neurons in NTS and gastric motility were assessed. NMDA in LH excited most of ghrelin-responsive gastric distension (GD)-sensitive neurons in NTS and promoted gastric motility. This effect was partially blocked by ghrelin antibody in NTS. Furthermore, the excitatory effects of NMDA in cisplatin-treated rats were weaker than those in saline-treated rats. Behaviorally, cisplatin induced a significant increase of kaolin consumption and decrease of food intake. These studies reveal a decreased expression of ghrelin in LH and up-regulation of GHS-R1a in LH and NTS, which are involved in the regulation of GD neuronal discharge in NTS and gastric motility.

Topics: Animals; Antibodies; Antineoplastic Agents; Cisplatin; Disease Models, Animal; Eating; Gastrointestinal Motility; Ghrelin; Hypothalamic Area, Lateral; Kaolin; Male; N-Methylaspartate; Neural Pathways; Neurotransmitter Agents; Random Allocation; Rats, Wistar; Receptors, Ghrelin; Solitary Nucleus

Hydrocephalus is usually associated with functional deficits which can be assessed by neurobehavioral tests. This study characterizes the neurobehavioral deficits occurring with increasing duration and severity of ventriculomegaly in an experimental neonatal hydrocephalic rat model. Hydrocephalus was induced in three weeks old albino rats by intracisternal injection of kaolin while controls received sterile water injection. They were sacrificed in batches at one, four and eight weeks post-injection after neurobehavioral tests (forelimb grip strength, open field and Morris water maze tests) were performed. The hydrocephalic rats were also categorized into mild, moderate and severe hydrocephalus based on ventricular size. The indices of muscular strength and vertical movements in severely hydrocephalic rats were 28.05 ± 5.19 seconds and 7.29 ± 2.71 rearings respectively, compared to controls (75.68 ± 8.58 seconds and 17.09 ± 1.25 rearings respectively). At eight weeks, vertical movements were significantly reduced in hydrocephalic rats compared to controls (3.14 ± 1.3 vs 13 ± 4.11 rearings). At one week, indices of learning and memory were significantly reduced in hydrocephalic rats, compared to controls (0.89±0.31 vs 3.88±1.01 crossings), but at 8 weeks, the indices were similar (2.56 ± 0.41 vs 3.33 ± 0.71 crossings). Untreated hydrocephalus is accompanied by decline in motor functions which increase with duration and severity of ventriculomegaly. However, cognitive deficits appear to partially recover.

Topics: Animals; Animals, Newborn; Behavior, Animal; Cognition; Disease Models, Animal; Disease Progression; Female; Hydrocephalus; Kaolin; Male; Maze Learning; Memory; Motor Activity; Muscle Strength; Nervous System; Rats, Wistar; Recovery of Function; Severity of Illness Index; Time Factors

OBJECTIVE There has been no established animal model of syringomyelia associated with lumbosacral spinal lipoma. The research on the pathophysiology of syringomyelia has been focused on Chiari malformation, trauma, and inflammation. To understand the pathophysiology of syringomyelia associated with occult spinal dysraphism, a novel animal model of syringomyelia induced by chronic mechanical compression of the lumbar spinal cord was created. METHODS The model was made by epidural injection of highly concentrated paste-like kaolin solution through windows created by partial laminectomy of L-1 and L-5 vertebrae. Behavioral outcome in terms of motor (Basso-Beattie-Bresnahan score) and urinary function was assessed serially for 12 weeks. Magnetic resonance images were obtained in some animals to confirm the formation of a syrinx and to monitor changes in its size. Immunohistochemical studies, including analysis for glial fibrillary acidic protein, NeuN, CC1, ED-1, and caspase-3, were done. RESULTS By 12 weeks after the epidural compression procedure, syringomyelia formation was confirmed in 85% of the rats (34 of 40) on histology and/or MRI. The syrinx cavities were found rostral to the epidural compression. Motor deficit of varying degrees was seen immediately after the procedure in 28% of the rats (11 of 40). In 13 rats (33%), lower urinary tract dysfunction was seen. Motor deficit improved by 5 weeks after the procedure, whereas urinary dysfunction mostly improved by 2 weeks. Five rats (13%, 5 of 40) died 1 month postoperatively or later, and 3 of the 5 had developed urinary tract infection. At 12 weeks after the operation, IHC showed no inflammatory process, demyelination, or accelerated apoptosis in the spinal cords surrounding the syrinx cavities, similar to sham-operated animals. CONCLUSIONS A novel experimental model for syringomyelia by epidural compression of the lumbar spinal cord has been created. The authors hope that it will serve as an important research tool to elucidate the pathogenesis of this type of syringomyelia, as well as the CSF hydrodynamics of the lumbar spinal cord.

Topics: Animals; Chronic Disease; Disease Models, Animal; Epidural Space; Immunohistochemistry; Kaolin; Laminectomy; Lumbar Vertebrae; Magnetic Resonance Imaging; Male; Motor Activity; Movement Disorders; Rats, Sprague-Dawley; Spinal Cord; Syringomyelia; Urination

Hydrocephalus is a complex disease that affects cerebrospinal fluid (CSF) dynamics and is very common in children. To this date, CSF shunting is still the standard treatment for childhood hydrocephalus, but, nevertheless, the effects of such an operation on the developing brain are widely unknown. To help overcome this, experimental models of CSF shunts are surely very useful tools.. The objective of this study was to describe a feasible and reliable technique of an adapted ventricular-subcutaneous shunt for the treatment of kaolin-induced hydrocephalus in young rats.. We developed a ventricular-subcutaneous shunt (VSCS) technique which was used in 31 Wistar young rats with kaolin-induced hydrocephalus. Hydrocephalus was induced at 7 days of age, and shunt implantation was performed 7 days later. Our technique used a 0.7-mm gauge polypropylene catheter tunneled to a subcutaneous pocket created over the animal's back and inserted into the right lateral ventricle. All animals were sacrificed 14 days after shunt insertion.. Twenty-four rats survived and remained well until the study was ended. No major complications were seen. Their weight gain went back to normal. They all underwent ambulatory behavioral testing prior and after VSCS, which showed improvement in their motor skills. We have also obtained magnetic resonance (MR) scans of 16 pups confirming reduction of ventricular size after shunting and indicating effective treatment. Histopathological analysis of brain samples before and after shunting showed reversion of ependymal and corpus callosum disruption, as well as fewer reactive astrocytes in shunted animals.. An experimental CSF shunt technique was devised. Excessive CSF of hydrocephalic rats is diverted into the subcutaneous space where it can be resorbed. This technique has a low complication rate and is effective. It might be applied to various types of experimental studies involving induction and treatment of hydrocephalus.

Topics: Analysis of Variance; Animals; Antidiarrheals; Brain; Catheters; Cerebrospinal Fluid Shunts; Disease Models, Animal; Glial Fibrillary Acidic Protein; Hydrocephalus; Infusions, Subcutaneous; Kaolin; Magnetic Resonance Imaging; Rats; Rats, Wistar

OBJECTIVE Syringomyelia pathophysiology is commonly studied using rodent models. However, in vivo studies of posttraumatic syringomyelia have been limited by the size of animals and lack of reliable noninvasive evaluation techniques. Imaging the rat spinal cord is particularly challenging because the spinal cord diameter is approximately 1-3 mm, and pathological lesions within the spinal cord parenchyma are even smaller. The standard technique has been histological evaluation, but this has its limitations. The aim of the present study was to determine whether syrinx size could be reliably measured using a preclinical high-field MRI animal system in a rat model of posttraumatic syringomyelia. METHODS The authors used an existing rat model of posttraumatic syringomyelia, which was created using a controlled pneumatic compression device to produce the initial spinal cord injury, followed by a subarachnoid injection of kaolin to produce arachnoiditis. T2-weighted MRI was performed on each animal using a 9.4-T scanner at 7, 10, and 13 weeks after injury. Animals were killed and syrinx sizes were calculated from in vivo MRI and histological studies. RESULTS MRI measurements of syrinx volume and length were closely correlated to histological measurements across all time points (Pearson product moment correlation coefficient r = ± 0.93 and 0.79, respectively). CONCLUSIONS This study demonstrates that high-field T2-weighted MRI can be used to measure syrinx size, and data correlate well with syrinx size measured using histological methods. Preclinical MRI may be a valuable noninvasive technique for tracking syrinx formation and enlargement in animal models of syringomyelia.

Topics: Animals; Arachnoiditis; Cysts; Disease Models, Animal; Disease Progression; Feasibility Studies; Image Processing, Computer-Assisted; Kaolin; Longitudinal Studies; Magnetic Resonance Imaging; Male; Organ Size; Rats, Sprague-Dawley; Spinal Cord Injuries; Syringomyelia; Time Factors

The goal of this study was to investigate the topical anti-inflammatory effects of the megamolecular polysaccharide sacran extracted from cyanobacterium Aphanothece sacrum using various inflammatory animal models. Sacran showed potent anti-inflammatory effects with optimum effective concentrations at 0.01 and 0.05% (w/v). Sacran markedly inhibited paw swelling and neutrophil infiltration in carrageenan-induced rat paw edema. Additionally, 6,7-dimethoxy-1-methyl-2(1H)-quinoxalinone-3-propionyl-carboxylic acid (DMEQ)-labeled sacran had the ability to penetrate carrageenan-induced rat paw skin rather than normal skin. Also, sacran significantly suppressed kaolin-induced and dextran-induced rat paw edema throughout the duration of the study. Furthermore, sacran significantly suppressed 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced mouse ear edema and mRNA expression levels of cyclooxygenase (COX)-2 as well as pro-inflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6. Safety of sacran solution was verified by negligible cytotoxicity in HaCaT cells. These results suggest that sacran may be useful as a therapeutic agent against inflammatory skin diseases with no life-threatening adverse effects.

Topics: Animals; Anti-Inflammatory Agents; Carrageenan; Cell Line; Cyanobacteria; Cyclooxygenase 2; Cytokines; Dextrans; Disease Models, Animal; Edema; Female; Humans; Kaolin; Male; Mice, Inbred BALB C; Polysaccharides; Quinoxalines; Rats; Rats, Wistar; Tetradecanoylphorbol Acetate

Three experiments were conducted showing rats' pica behavior (kaolin clay intake) due to running in activity wheels. The amount of kaolin consumed was a positive function of the available time of voluntary running (20, 40, or 60 min), although this relationship was blunted by a descending (i.e., 60 → 40 → 20 min) test series of execution (Experiment 1). Pica was also generated by forced running in a motorized wheel for 60 min as a positive function of the speed of wheel rotations at 98, 185, or 365 m/h, independent of the order of execution (Experiment 2). Voluntary running generated more pica than did forced running at 80 m/h, although the distance travelled in the former condition was 27% lesser than that in the latter condition (Experiment 3). Because kaolin intake is regarded as a reliable measure of nausea in rats, these results show that wheel running, either voluntary or forced, induces nausea in rats.

Topics: Aluminum Silicates; Animals; Behavior, Animal; Clay; Disease Models, Animal; Energy Intake; Feeding Behavior; Kaolin; Male; Motor Activity; Nausea; Physical Exertion; Pica; Rats, Wistar; Reproducibility of Results; Time Factors

In an effort to develop novel treatments for communicating hydrocephalus, we have shown previously that the transforming growth factor-β antagonist, decorin, inhibits subarachnoid fibrosis mediated ventriculomegaly; however decorin's ability to prevent cerebral cytopathology in communicating hydrocephalus has not been fully examined. Furthermore, the capacity for diffusion tensor imaging to act as a proxy measure of cerebral pathology in multiple sclerosis and spinal cord injury has recently been demonstrated. However, the use of diffusion tensor imaging to investigate cytopathological changes in communicating hydrocephalus is yet to occur. Hence, this study aimed to determine whether decorin treatment influences alterations in diffusion tensor imaging parameters and cytopathology in experimental communicating hydrocephalus. Moreover, the study also explored whether diffusion tensor imaging parameters correlate with cellular pathology in communicating hydrocephalus.. Accordingly, communicating hydrocephalus was induced by injecting kaolin into the basal cisterns in 3-week old rats followed immediately by 14 days of continuous intraventricular delivery of either human recombinant decorin (n = 5) or vehicle (n = 6). Four rats remained as intact controls and a further four rats served as kaolin only controls. At 14-days post-kaolin, just prior to sacrifice, routine magnetic resonance imaging and magnetic resonance diffusion tensor imaging was conducted and the mean diffusivity, fractional anisotropy, radial and axial diffusivity of seven cerebral regions were assessed by voxel-based analysis in the corpus callosum, periventricular white matter, caudal internal capsule, CA1 hippocampus, and outer and inner parietal cortex. Myelin integrity, gliosis and aquaporin-4 levels were evaluated by post-mortem immunohistochemistry in the CA3 hippocampus and in the caudal brain of the same cerebral structures analysed by diffusion tensor imaging.. Decorin significantly decreased myelin damage in the caudal internal capsule and prevented caudal periventricular white matter oedema and astrogliosis. Furthermore, decorin treatment prevented the increase in caudal periventricular white matter mean diffusivity (p = 0.032) as well as caudal corpus callosum axial diffusivity (p = 0.004) and radial diffusivity (p = 0.034). Furthermore, diffusion tensor imaging parameters correlated primarily with periventricular white matter astrocyte and aquaporin-4 levels.. Overall, these findings suggest that decorin has the therapeutic potential to reduce white matter cytopathology in hydrocephalus. Moreover, diffusion tensor imaging is a useful tool to provide surrogate measures of periventricular white matter pathology in communicating hydrocephalus.

Topics: Animals; Aquaporin 4; Atrophy; Brain; Child; Decorin; Diffusion Magnetic Resonance Imaging; Diffusion Tensor Imaging; Disease Models, Animal; Glial Fibrillary Acidic Protein; Humans; Hydrocephalus; Immunohistochemistry; Kaolin; Myelin Sheath; Neuroprotective Agents; Random Allocation; Rats, Sprague-Dawley; Recombinant Proteins; Transforming Growth Factor beta; White Matter

The pathogenesis of adult chronic hydrocephalus is not fully understood, and the temporal relationship between development of the radiological changes and neurological deterioration is unknown.. To clarify the progression of radiological-histological changes and subsequent clinical manifestations of adult chronic hydrocephalus.. Kaolin was injected bilaterally into the subarachnoid space overlying the cranial convexities in 20 adult rats. Magnetic resonance imaging (MRI) was obtained by using an 11.7 T scanner at 14, 60, 90, and 120 days after kaolin injection. Locomotor, gait, and cognitive evaluations were performed independently. Kaolin distribution and the associated inflammatory and fibrotic responses were histologically analyzed.. Evans index of ventriculomegaly showed significant progressive growth in ventricular size over all time points examined. The greatest enlargement occurred within the first 2 months. Evans index also correlated with the extent of kaolin distribution by MRI and by pathological examination at all time points. First gait changes occurred at 69 days, anxiety at 80, cognitive impairment at 81, and locomotor difficulties after 120 days. Only locomotor deterioration was associated with Evans index or the radiological evaluation of kaolin extension. Inflammatory/fibrotic response was histologically confirmed over the cranial convexities in all rats, and its extension was associated with ventricular size and with the rate of ventricular enlargement.. Kaolin injected into the subarachnoid space over the cerebral hemispheres of adult rats produces an inflammatory/fibrotic response leading in a slow-onset communicating hydrocephalus that is initially asymptomatic. Increased ventricular size eventually leads to gait, memory, and locomotor impairment closely resembling the course of human adult chronic hydrocephalus.. NPH, normal pressure hydrocephalus.

Topics: Animals; Cognition; Disease Models, Animal; Female; Fibrosis; Gait; Hydrocephalus; Hydrocephalus, Normal Pressure; Inflammation; Kaolin; Locomotion; Magnetic Resonance Imaging; Radiography; Rats; Rats, Sprague-Dawley; Subarachnoid Space

Neuroplastic changes in the amygdala account for emotional-affective aspects of pain and involve neuropeptides such as calcitonin gene-related peptide and corticotropin-releasing factor. Another neuropeptide system, central arginine vasopressin, has been implicated in neuropsychiatric disorders, but its role in pain-related emotional expression and neuroplasticity remains to be determined. Here, we tested the hypothesis that arginine vasopressin in the amygdala contributes to pain-related emotional-affective responses, using stereotaxic applications of arginine vasopressin and antagonists for G-protein coupled vasopressin V1A and oxytocin receptors in adult male Sprague-Dawley rats. In normal animals, arginine vasopressin increased audible and ultrasonic vocalizations and anxiety-like behavior (decreased open-arm preference in the elevated plus maze). The facilitatory effects were blocked by a selective V1A antagonist (SR 49059, Relcovaptan) but not by an oxytocin receptor antagonist (L-371,257). L-371,257 had some facilitatory effects on vocalizations. Arginine vasopressin had no effect in arthritic rats (kaolin/carrageenan knee joint pain model). SR 49059 inhibited vocalizations and anxiety-like behavior (elevated plus maze) in arthritic, but not normal, rats and conveyed anxiolytic properties to arginine vasopressin. Arginine vasopressin, SR 49059, and L-371,257 had no significant effects on spinal reflexes. We interpret the data to suggest that arginine vasopressin through V1A in the amygdala contributes to emotional-affective aspects of pain (arthritis model), whereas oxytocin receptors may mediate some inhibitory effects of the vasopressin system.

Topics: Amygdala; Animals; Arthritis; Benzoxazines; Carrageenan; Disease Models, Animal; Hormone Antagonists; Indoles; Kaolin; Male; Maze Learning; Microdialysis; Pain; Piperidines; Pyrrolidines; Rats; Rats, Sprague-Dawley; Receptors, Oxytocin; Receptors, Vasopressin; Reflex; Vocalization, Animal

intra-articular co-injection of kaolin with carrageenan (CGN) in rodents is widely used as an experimental model of arthritis. However, the ability of kaolin to cause arthritis and related immune responses when administered alone is unclear. We evaluated the contribution of prostanoids and sensory C-fibres (and their neuropeptide substance P) to kaolin-induced inflammation in the rat knee.. Wistar rats, 8-10 weeks old, received an intra-articular injection of kaolin (1-10 μg/joint) or saline into the knee joint. Knee inflammation, proinflammatory cytokines, pain behaviour and secondary tactile allodynia were assessed over 5 h, when synovial leukocyte counts, histopathological changes and proinflammatory cytokine levels were evaluated.. The intra-articular injection of kaolin caused a dose- and time-dependent knee swelling and impairment of motion that were associated with secondary tactile allodynia, elevated concentrations of IL-1β, IL-6 and TNFα, leukocyte infiltration, and histopathological changes in the ipsilateral hindpaw. The neurokinin-1 (NK1) receptor antagonist SR140333 or neonatal treatment with capsaicin markedly reduced the inflammatory parameters, cytokines and allodynia but failed to significantly inhibit the impaired motion. The cyclo-oxygenase inhibitor indomethacin partially inhibited knee oedema and allodynia but did not affect the leukocyte influx, myeloperoxidase activity or impaired motion in the kaolin-injected rat.. We show the first evidence that intra-articular injection of kaolin without CGN produced severe acute monoarthritis. This was highly dependent on substance P (released from C-fibres) and NK1 receptor activation, which stimulated local production of proinflammatory cytokines. This model may be of critical importance for mechanistic studies and screening new anti-inflammatory/analgesic drugs.

Topics: Animals; Animals, Newborn; Antidiarrheals; Arthritis; Capsaicin; Cytokines; Disease Models, Animal; Edema; Enzyme Inhibitors; Hyperalgesia; Indomethacin; Kaolin; Knee Joint; Male; Pain Measurement; Peroxidase; Piperidines; Quinuclidines; Rats; Rats, Wistar; Receptors, Neurokinin-1; Synovial Fluid

Intermittent subcutaneous injection of teriparatide, an active fragment of human parathyroid hormone, is clinically used for the treatment of osteoporosis. Patients suffer from nausea, which is one of the side effects teriparatide induces; however, the etiology of teriparatide-induced nausea remains unknown. We have reported pica, kaolin ingestion behavior, can be used as an assessment of nausea-related response in rats. In this study, we investigated the characteristics of teriparatide-induced pica and the abilities of anti-emetic drugs to inhibit teriparatide-induced pica. Male and female adolescent (4-week-old), young (8-week-old), and adult (30-week-old) naive rats, and ovariectomized (OVX: 17-week-old) and sham-operated (17-week-old) rats subcutaneously received teriparatide (0.4 mg/kg, n=4), and their kaolin and food intakes were monitored for 24 h after the injection. Among the tested rats, we found that OVX rats, rather than male, female, and sham-operated rats, showed marked teriparatide-induced pica (0 mg/kg: 0.17±0.07 g, 0.4 mg/kg: 6.18±0.91 g). Teriparatide-induced pica in OVX rats was inhibited by intraperitoneal pretreatment with serotonin 5-HT3 (granisetron 0.5 mg/kg), dopamine D2 (prochlorperazine 0.5 mg/kg), neurokinin NK1 (fosaprepitant 1 mg/kg), and histamine H1 (diphenhydramine 10 mg/kg) receptor antagonists to 70%, 11%, 19%, and 59% of that in vehicle-treated control, respectively. These results suggest that teriparatide-induced pica in OVX rats has the potential to reflect teriparatide-induced nausea; 5-HT3, D2, NK1, and H1 receptor activation is involved in the development of this behavior; antagonists of these receptors have the potential to be medical candidates used as treatments for teriparatide-induced nausea in human patients.

Topics: Age Factors; Animals; Anorexia; Antiemetics; Diphenhydramine; Disease Models, Animal; Dopamine D2 Receptor Antagonists; Dose-Response Relationship, Drug; Eating; Feeding Behavior; Female; Granisetron; Histamine H1 Antagonists; Kaolin; Male; Morpholines; Nausea; Neurokinin-1 Receptor Antagonists; Neurotransmitter Agents; Ovariectomy; Pica; Prochlorperazine; Rats, Wistar; Serotonin 5-HT3 Receptor Antagonists; Teriparatide

The goal of this study was to identify direct cerebrospinal fluid (CSF) pathways in the interface between ventricles and cisterns. Such routes are hypothesized to be involved in alternative CSF flows in abnormal circumstances of CSF circulation.. Chronic obstructive hydrocephalus models were induced in ten Sprague-Dawley rats with kaolin injection into the cisterna magna. Three weeks after the kaolin injection, when thick arachnoid fibrosis obliterated the fourth ventricular outlets, cationized ferritin was stereotactically infused as a tracer into the lateral ventricle in order to observe the pathways from the ventricles to the subarachnoid space. Animals were killed in 48 h and brains were sectioned. CSF flow pathways were traced by the staining of ferritin with ferrocyanide.. Eight out of ten rats developed hydrocephalus. The subarachnoid membranes of the convexity and basal cisterns were severely adhered such that most of the ferritin remained in the ventricles whereas basal and convexity cisterns were clear of ferritin. In six out of the eight hydrocephalus rats, ferritin leaked from the third ventricle into the quadrigeminal cistern, and from the lateral ventricle into the ambient cistern.. The interfaces between the third ventricle and the quadrigeminal cistern, and between the lateral ventricle and the ambient cistern appear to be alternative CSF pathways in a pathologic condition such as obstructive hydrocephalus.

Topics: Animals; Antidiarrheals; Cerebrospinal Fluid; Cisterna Magna; Disease Models, Animal; Ferritins; Hydrocephalus; Kaolin; Male; Rats; Rats, Sprague-Dawley; Third Ventricle

To develop an experimental model of neurocysticercosis-induced hydrocephalus. There were used 17 rats. Ten animals were inoculated with Taenia crassiceps cysts into the subarachnoid. Five animals were injected with 0. ml of 25% kaolin (a standard solution for the development of experimental hydrocephalus) and two animals were injected with saline. Magnetic resonance imaging (MRI) was used to evaluate enlargement of the ventricles after one or three months of inoculation. Volumetric study was used to quantify the ventricle enlargement.. Seven of the 10 animals in the cyst group developed hydrocephalus, two of them within one month and five within three months after inoculation. Three of the five animals in the kaolin group had hydrocephalus and none in the saline group. Ventricle volumes were significantly higher in the 3-months MRI cyst subgroup than in the 1-month cyst subgroup. Differences between cyst subgroups and kaolin group did not reach statistical significance.. The developed model may reproduce the human condition of neurocysticercosis-related hydrocephalus, which exhibits a slowly progressive chronic course.

Topics: Animals; Cerebral Ventricles; Disease Models, Animal; Hydrocephalus; Kaolin; Magnetic Resonance Imaging; Neurocysticercosis; Pilot Projects; Rats, Wistar; Taenia

Affective disorders are common comorbidities of chronic inflammatory pain that are often overlooked in primary care. As the impact of inflammatory pain upon mood-like disorders in animal models is not well known, our objective was to assess whether prolonged experimental monoarthritis (ARTH) induced the development of anxiety and depressive-like behaviours in rodents and if amitriptyline, an antidepressant commonly used in the treatment of chronic pain, could reverse both nociceptive and mood-like impairments. Experimental ARTH was induced through an injection of kaolin/carrageenan into the right knee joint with control (SHAM) animals injected with saline. Four weeks after induction, ARTH animals displayed mechanical hyperalgesia and a depressive-like phenotype as they showed a significant increase in immobility and a decrease in the latency to immobility in the forced-swimming test at the expense of the time spent climbing/swimming. ARTH animals also displayed a decreased sucrose preference, an index of anhedonia and anxiety-like behaviour as time spent exploring the open arms of the elevated-plus-maze was decreased when compared to controls. The anxiety-like phenotype was also supported by an increase in the number of fecal boli left in the open field. In ARTH animals, the administration of amitriptyline decreased mechanical hyperalgesia and increased sucrose preference and the time spent climbing, although it had a deleterious effect in the performance of control animals. Our data show that this model of ARTH can be useful for the study of chronic pain-mood disorders comorbidities and that amitriptyline is able to partly reverse the associated nociceptive and emotional impairments.

Topics: Amitriptyline; Analgesics, Non-Narcotic; Animals; Arthritis; Carrageenan; Disease Models, Animal; Exploratory Behavior; Food Preferences; Hyperalgesia; Kaolin; Male; Maze Learning; Mood Disorders; Motor Activity; Pain Threshold; Physical Stimulation; Rats; Rats, Wistar; Swimming

Ventriculomegaly occurs when there is imbalance between creation and absorption of cerebrospinal fluid (CSF); even when treated, long-term behavioral changes occur. Kaolin injection in the cisterna magna of rats produces an obstruction of CSF outflow and models one type of hydrocephalus. Previous research with this model shows that neonatal onset has mixed effects on Morris water maze (MWM) and motoric performance; we hypothesized that this might be because the severity of ventricular enlargement was not taken into consideration. In the present experiment, rats were injected with kaolin or saline on postnatal day (P)21 and analyzed in subgroups based on Evan's ratios (ERs) of the severity of ventricular enlargement at the end of testing to create 4 subgroups from least to most severe: ER0.4-0.5, ER0.51-0.6, ER0.61-0.7, and ER0.71-0.82, respectively. Locomotor activity (dry land and swimming), acoustic startle with prepulse inhibition (PPI), and MWM performance were tested starting on P28 (122cm maze) and again on P42 (244cm maze). Kaolin-treated animals weighed significantly less than controls at all times. Differences in locomotor activity were seen at P42 but not P28. On P28 there was an increase in PPI for all but the least severe kaolin-treated group, but no difference at P42 compared with controls. In the MWM at P28, all kaolin-treated groups had longer path lengths than controls, but comparable swim speeds. With the exception of the least severe group, probe trial performance was worse in the kaolin-treated animals. On P42, only the most severely affected kaolin-treated group showed deficits compared with control animals. This group showed no MWM learning and no memory for the platform position during probe trial testing. Swim speed was unaffected, indicating motor deficits were not responsible for impaired learning and memory. These findings indicate that kaolin-induced ventriculomegaly in rats interferes with cognition regardless of the final enlargement of the cerebral ventricles, but final size critically determines whether lasting locomotor, learning, and memory impairments occur.

Topics: Animals; Chronic Disease; Disease Models, Animal; Hydrocephalus; Kaolin; Learning Disabilities; Male; Maze Learning; Memory Disorders; Mental Disorders; Movement Disorders; Rats; Rats, Sprague-Dawley; Weaning

The efficacy of thalidomide to attenuate cisplatin-induced emesis was evaluated in a rat model. Four groups were utilized: control group (peritoneal injection and gastric lavage with normal saline), cisplatin group (peritoneal injection of cisplatin at 10 mg/kg and gastric lavage with normal saline), thalidomide group (cisplatin as above and gastric lavage with thalidomide at 10 mg/kg), and granisetron group (positive control for antiemetic effects; cisplatin given as above and gastric lavage done with granisetron at 0.5 mg/kg). The cisplatin-induced kaolin consumption (pica behavior) was used as a model of emesis in patients. The animals' kaolin and food intakes were measured. Further, medulla and gastric tissues were obtained 5 and 33 h after peritoneal injections to quantify the levels of Substance P and Neurokinin-1 receptor (NK-1R). The cisplatin-induced kaolin consumption was significantly (p < 0.05 vs. cisplatin group) attenuated by thalidomide 72 h after the injection. The levels of Substance P in the medulla and gastric tissue were increased 5 h after the injection in both cisplatin and thalidomide groups, however, returned faster to normal levels in the thalidomide group (p < 0.05 vs. cisplatin group). Further, levels of NK-1R in the cisplatin, thalidomide, and granisetron group were significantly increased at both 5 and 33 h (p < 0.05 vs. control group), with no obvious difference among these three groups. In conclusion, thalidomide attenuates animal equivalent of cisplatin-induced emesis, and this beneficial effect is associated with decreased levels of Substance P levels in the medulla and gastric tissue.

Topics: Animals; Antiemetics; Antineoplastic Agents; Cisplatin; Disease Models, Animal; Eating; Kaolin; Male; Rats; Rats, Wistar; Receptors, Neurokinin-1; Substance P; Thalidomide; Vomiting

Recently discovered neuropeptide S (NPS) has anxiolytic and pain-inhibiting effects in rodents. We showed previously that NPS increases synaptic inhibition of amygdala output to inhibit pain behaviors. The amygdala plays a key role in emotional-affective aspects of pain. Of clinical significance is that NPS can be applied nasally to exert anxiolytic effects in rodents. This study tested the novel hypothesis that nasal application of NPS can inhibit pain-related behaviors in an arthritis model through NPS receptors (NPSR) in the amygdala. Behaviors and electrophysiological activity of amygdala neurons were measured in adult male Sprague Dawley rats. Nasal application of NPS, but not saline, inhibited audible and ultrasonic vocalizations and had anxiolytic-like effects in the elevated plus-maze test in arthritic rats (kaolin/carrageenan knee joint arthritis model) but had no effect in normal rats. Stereotaxic application of a selective non-peptide NPSR antagonist (SHA68) into the amygdala by microdialysis reversed the inhibitory effects of NPS. NPS had no effect on hindlimb withdrawal thresholds. We showed previously that intra-amygdala application of an NPSR antagonist alone had no effect. Nasal application of NPS or stereotaxic application of NPS into the amygdala by microdialysis inhibited background and evoked activity of amygdala neurons in arthritic, but not normal, anesthetized rats. The inhibitory effect was blocked by a selective NPSR antagonist ([D-Cys(tBu)5]NPS). In conclusion, nasal application of NPS can inhibit emotional-affective, but not sensory, pain-related behaviors through an action in the amygdala. The beneficial effects of non-invasive NPS application may suggest translational potential.

Topics: Administration, Intranasal; Amygdala; Analgesics; Animals; Arthritis; Carrageenan; Disease Models, Animal; Hyperalgesia; Kaolin; Knee Joint; Male; Maze Learning; Neurons; Neuropeptides; Pain; Rats; Rats, Sprague-Dawley; Reflex; Spinal Cord; Vocalization, Animal

Voluntary running in an activity wheel establishes aversion to paired taste in rats. A proposed mechanism underlying this taste aversion learning is gastrointestinal discomfort caused by running. We tested this hypothesis by measuring the pica behavior (kaolin clay intake) of rats, because it is known that rats engage in pica behavior after various nausea-inducing treatments including irradiation, motion sickness, and injection of emetic drugs such as lithium chloride (LiCl). Following a demonstration of the already-known phenomenon of LiCl-based pica in Experiment 1, we successfully showed running-based pica behavior in Experiment 2 where the running treatment was compared with a non-running control treatment (i.e., confinement in a locked wheel). These results suggest that not only LiCl but also running induces nausea in rats, supporting the gastrointestinal discomfort hypothesis of running-based taste aversion learning.

Topics: Abdominal Pain; Aluminum Silicates; Animals; Avoidance Learning; Behavior, Animal; Clay; Disease Models, Animal; Dysgeusia; Emetics; Injections, Intraperitoneal; Kaolin; Lithium Chloride; Male; Models, Biological; Motor Activity; Nausea; Physical Exertion; Pica; Rats, Wistar; Stress, Physiological

Severe hepatic injuries may be highly lethal, and perihepatic packing remains the mainstay of treatment. This is not always successful, particularly in the setting of hypothermia and coagulopathy. Kaolin-impregnated Combat Gauze (CG) is an effective hemostatic dressing used primarily to treat external wounds. The objective of this study was to determine the ability of CG to control severe hemorrhage in hypothermic, coagulopathic swine with a high-grade hepatic injury.. Anesthetized animals underwent splenectomy and were cooled to 32°C while undergoing a 60% exchange transfusion with Hextend. A grade V liver injury was created in the left middle hepatic lobe. Animals were allowed to freely bleed for 30 s and then randomized to treatment with CG or plain gauze laparotomy pads (PG) applied to the injury site. Animals were then resuscitated with warmed Hextend.. There was no difference between groups in preinjury hemodynamic or laboratory values. Animals packed with CG had less blood loss when compared with standard packing (CG = 25 mL/kg versus PG = 58 mL/kg, P = 0.05). There was a trend towards lower hetastarch resuscitation requirements in the CG group (CG = 7 mL/kg versus PG = 44 mL/kg, P = 0.06) but no statistically significant difference in mortality (CG = 13% versus PG = 50%, P = 0.11). Histology of the injury sites revealed more adherent clot in the CG group, but no inflammation, tissue necrosis, or residual material.. In pigs with severe hepatic injury, Combat Gauze reduced blood loss and resuscitation requirements when compared with plain laparotomy pads. Combat Gauze may be safe and effective for use on severe liver injuries.

Topics: Animals; Bandages; Blood Coagulation Disorders; Disease Models, Animal; Female; Hemorrhage; Hemostatic Techniques; Hemostatics; Hypothermia, Induced; Incidence; Inflammation; Kaolin; Liver; Male; Necrosis; Pilot Projects; Swine; Treatment Outcome

Nausea and vomiting are considered as the foremost unpleasant side effects of chemotherapy experienced by 20-90% of cancer patients.. In the present study, the effects of Korean Panax ginseng C.A. Meyer (Araliaceae) (RG), ginseng saponin (GS) and non-saponin (GNS) on cisplatin (CP)-induced pica and gastric damage in rats were investigated.. Rats were treated with RG (25, 50, 100 mg/kg b.wt.), GS (5 and 10 mg/kg 100 mg/kg b.wt.) and GNS (50 and 100 mg/kg b.wt.) before or after a single intraperitoneal injection of CP (6 mg/kg b.wt.). Kaolin together with normal food intake, normal food alone, body weight, histological examination of stomach and small intestine were used as indices of CP-induced pica in rats.. Pre-treatment with RG (50 and 100 mg/kg b.wt.) attenuated CP-induced kaolin intake at 24 h. CP-induced kaolin intake decreased upon post-treatment of rats with RG (50 and 100 mg/kg b.wt.) at 48 h. The incidence of body weight reduction at 48 and 72 h diminished in rats post-treated with RG (50 mg/kg b.wt.). Pre-treatment with GS (5 and 10 mg/kg b.wt.) and GNS (50 and 100 mg/kg b.wt.) attenuated CP-induced kaolin intake while normal food intake was not improved in 24 and 48 h.. The gastro-protective effects of RG, GS and GNS were further confirmed by histopathological (damage in glandular portion and villi with dilated appearance) findings. The study indicates that both the red GS and GNS improve feeding behavior against CP-induced pica in rats.

Topics: Animals; Antineoplastic Agents; Body Weight; Cisplatin; Disease Models, Animal; Dose-Response Relationship, Drug; Eating; Injections, Intraperitoneal; Intestine, Small; Kaolin; Male; Panax; Pica; Plant Extracts; Rats; Rats, Sprague-Dawley; Saponins; Stomach; Time Factors

In post-haemorrhagic and other forms of communicating hydrocephalus, cerebrospinal fluid flow and drainage is obstructed by subarachnoid fibrosis in which the potent fibrogenic cytokine transforming growth factor-β has been aetiologically implicated. Here, the hypothesis that the transforming growth factor-β antagonist decorin has therapeutic potential for reducing fibrosis and ventriculomegaly was tested using a rat model of juvenile communicating hydrocephalus. Hydrocephalus was induced by a single basal cistern injection of kaolin in 3-week-old rats, immediately followed by 3 or 14 days of continuous intraventricular infusion of either human recombinant decorin or phosphate-buffered saline (vehicle). Ventricular expansion was measured by magnetic resonance imaging at Day 14. Fibrosis, transforming growth factor-β/Smad2/3 activation and hydrocephalic brain pathology were evaluated at Day 14 and the inflammatory response at Days 3 and 14 by immunohistochemistry and basic histology. Analysis of ventricular size demonstrated the development of hydrocephalus in kaolin-injected rats but also revealed that continuous decorin infusion prevented ventricular enlargement, such that ventricle size remained similar to that in intact control rats. Decorin prevented the increase in transforming growth factor-β1 and phosphorylated Smad2/3 levels throughout the ventricular system after kaolin injection and also inhibited the deposition of the extracellular matrix molecules, laminin and fibronectin in the subarachnoid space. In addition, decorin protected against hydrocephalic brain damage inferred from attenuation of glial and inflammatory reactions. Thus, we conclude that decorin prevented the development of hydrocephalus in juvenile rats by blocking transforming growth factor-β-induced subarachnoid fibrosis and protected against hydrocephalic brain damage. The results suggest that decorin is a potential clinical therapeutic for the treatment of juvenile post-haemorrhagic communicating hydrocephalus.

Topics: Analysis of Variance; Animals; Brain; CD11b Antigen; Decorin; Disease Models, Animal; Drug Delivery Systems; Ependyma; Fibronectins; Fibrosis; Glial Fibrillary Acidic Protein; Humans; Hydrocephalus; Kaolin; Magnetic Resonance Imaging; Rats; Rats, Sprague-Dawley; Rec A Recombinases; Smad2 Protein; Subarachnoid Space; Time Factors; Transforming Growth Factor beta1

The purpose of this study was to evaluate the long-term efficacy and safety of kaolin- and chitosan-based hemostatic agents for hemorrhage control in a 14-day survival, damage-control swine model of Grade IV liver injury.. A total of 48 anesthetized pigs (40 kg) underwent a 35% total blood volume bleed, cooling to 34°C and a standardized liver injury. The animals were randomized to standard gauze control (SG, n = 12), QuikClot Combat Gauze (QCCG, n = 12), Celox (CX, n = 12), or Celox Gauze (CXG, n = 12) packing. At 15 minutes, shed blood was calculated, followed by damage-control closure. At 48 hours, pack removal and definitive closure was performed. At 14-day sacrifice, the liver, kidney, heart, lung, and small bowel standard intra-abdominal organs were sampled for histopathological examination.. Uncontrolled blood loss at 2 minutes demonstrated internal consistency of the injury. Blood loss at 15 minutes was significantly lower in the CX and QCCG arms (SG, 11.1 ± 1.1 mL/kg; QCCG, 5.3 ± 1.2 mL/kg; CX, 5.7 ± 1.2 mL/kg; and CXG, 10.1 ± 1.3 mL/kg; p = 0.002). Forty-eight-hour survival was 50.0% for SG, 58.3% for QCCG, 83.3% for CX, and 41.7% for CXG (p = 0.161). Fourteen-day survival was 41.7% (5) for SG, 50.0% (6) for QCCG, 58.3% (7) for CX, and 41.7% (5) for CXG (p = 0.821). Four CX and two QCCG deaths were caused by bowel obstruction; one SG death was caused by sepsis; the remainder was caused by blood loss.Histopathology in one CX animal demonstrated eosinophilic material within a coronary vessel consistent with granule embolization.. Celox and QuikClot Combat Gauze were effective hemostatic adjuncts to standard intracavitary damage-control packing. The hemostasis was durable, facilitating pack removal, and definitive closure at reoperation. There was however an increase in the development of intra-abdominal adhesions resulting in small bowel obstruction. The potential for distant embolization of granular agents warrants further investigation.

Topics: Animals; Chitosan; Disease Models, Animal; Female; Hemorrhage; Hemostatics; Intestine, Small; Kaolin; Kidney; Liver; Myocardium; Swine

We previously reported that motion sickness was prevented in rats with amygdala lesion and that provocative motion stimuli increased the number of Fos-positive neurons in the amygdala, suggesting that the amygdala is one of the neural substrates involved in the development of motion sickness. NK-1 receptors in the brain stem and amygdala are thought to play an important role in emesis and affective disorders, respectively. In the present study, to elucidate a role of substance P neuronal system and NK-1 receptors in the brain stem and amygdala in the development of motion sickness, we measured changes in gene expression of NK-1 receptors and preprotachykinin, a precursor of substance P, using quantitative real-time PCR methods in solitary tract nucleus and amygdala in rats after provocative motion stimuli induced by 2G hypergravity load. Effects of systemic administration of CP-99,994, an antagonist for NK-1 receptors, on hypergravity-induced motion sickness were also examined using pica behavior, eating non-nutritive substances such as kaolin, as an index of motion sickness in rats. Hypergravity-induced motion sickness was inhibited by CP-99,994 with a dose-dependent and enantioselective manner. Preprotachykinin mRNA expression was increased in basolateral nucleus of amygdala and solitary tract nucleus after hypergravity load for 3h, whereas NK-1 receptor mRNA expression was not changed by hypergravity in amygdala and solitary tract nucleus. Present results suggest that 2G hypergravity load activated the substance P neuronal system in amygdala as well as in the brain stem and this activation would be related to the development of motion sickness.

Topics: Amygdala; Analysis of Variance; Animals; Brain Stem; Disease Models, Animal; Eating; Gene Expression Regulation; Hypergravity; Kaolin; Male; Motion Sickness; Neurokinin-1 Receptor Antagonists; Piperidines; Protein Precursors; Rats; Rats, Wistar; Receptors, Neurokinin-1; RNA, Messenger; Tachykinins; Time Factors

Mechanisms underlying the development of noncommunicating syringomyelia are poorly understood.. To assess the influence of focal arachnoiditis and central canal (CC) occlusion (CCO) on the formation of noncommunicating syringomyelia in the adult rat cervical spinal cord. Expression of pericanalicular aquaporin-4 is also examined.. Sprague-Dawley rats were subjected to circumferential or dorsal arachnoiditis (n = 34). Rats undergoing CCO (n = 69) were divided into 4 groups: group A, kaolin injection at a single site in the dorsal columns near the CC; group B, kaolin injection at multiple sites in the dorsal columns near the CC; group C, saline injection at multiple sites in the dorsal columns near the CC; or group D, controls. Rats were killed at 1, 4, 8, and 12 weeks. The CC area and aquaporin-4 (AQP4) expression were measured at the level of maximal CC enlargement.. Circumferential and dorsal arachnoiditis induced a mild increase in the CC area at 12 weeks. Single-site CCO induced slight CC enlargement. In contrast, multiple sites of CCO in proximity frequently induced a major expansion of the CC area (up to 50 times). Increased AQP4 expression was observed in pericanalicular astrocytes proportional to the degree of CC expansion.. Multiple sites of CCO created a model of noncommunicating syringomyelia in adult rats. Increased astrocytic AQP4 expression was proportional to the degree of CC expansion. Modulation of aquaporin expression may be a novel target for therapeutic interventions to prevent syringomyelia.

Topics: Animals; Aquaporin 4; Arachnoiditis; Cervical Vertebrae; Disease Models, Animal; Female; Gene Expression Regulation; Kaolin; Laminectomy; Rats; Rats, Sprague-Dawley; Spinal Canal; Spinal Stenosis; Syringomyelia; Time Factors

Battlefield hemorrhage remains the primary cause of death in potentially survivable combat injuries with noncompressible hemorrhage. Fibrin dressings have great potential for reducing mortality, however are limited by cost, availability, and disease transmission.. Dressings comprising a soluble dextran dressing with lyophilized salmon thrombin and fibrinogen (STF) were tested against Combat Gauze (CG) as a control in a standard swine femoral artery hemorrhage model. Ten female swine were used in each arm of the study.. Survival, blood loss, and time to hemostasis were similar between the two dressings. Two of the CGtreated animals that survived exsanguinated during the simulated walking maneuver. Three CG-treated animals formed a clot within the wound, but the clot did not adhere to the femoral artery injury. All ten of the STF-treated animals formed a clot in the wound that adhered and sealed the arterial injury site, even in three animals that did not survive. None of the STF-treated animals bled following the simulated walking maneuver. Three of five STF-treated animals reestablished blood flow distal to the injury as demonstrated by angiography.. The STF dressing is as efficacious as CG in treating hemorrhage in this model of a lethal injury. Further, the STF dressing formed a fibrin sealant over the injury, whereas CG achieved hemostasis by occlusive compression of the artery. The sealant property of the STF dressing allowed reestablishment of antegrade blood flow into the distal limb, demonstrating that this dressing has the potential of limb salvage in addition to control of life-threatening hemorrhage.

Topics: Animals; Bandages; Disease Models, Animal; Fibrinogen; Hemorrhage; Hemostatic Techniques; Kaolin; Salmon; Swine; Thrombin

Joints are privileged compartments that enjoy increased protection against the inflammatory reactions affecting the extremities. We hypothesized that the functional characteristics of the microvasculature would contribute to the differential defensive potential of the synovial membrane.. We investigated the synovial microcirculatory reactions and compared them with those of the tibial periosteum in response to 60 min of total limb ischemia, followed by 180 min of ischemia-reperfusion (IR) in rats. Carrageenan/kaolin-induced knee monoarthritis, a neutrophil-driven synovial inflammation model, served as the positive control.. IR brought about a significant reduction in red blood cell velocity in the capillaries and increases in rolling and adherence of the neutrophil leukocytes in the postcapillary venules (intravital microscopy), in adhesion molecule expression (intercellular adhesion molecule-1 immunohistochemistry) and in xanthine oxidoreductase activity in the periosteum. These changes were also pronounced in carrageenan/kaolin-induced monoarthritis but were almost completely absent in the synovium after the IR challenge. Most importantly, even after IR and in carrageenan/kaolin monoarthritis, the synovial microcirculation was characterized by significantly greater red blood cell velocities than that in the periosteum under resting conditions.. The ischemic duration, which significantly affected the functional integrity of the periosteal microcirculation, did not bring about a marked deterioration in that of the synovial membrane, suggesting that the synovial microcirculation is less endangered to the consequences of short-term tourniquet exposure than the periosteum. The greater microcirculatory red blood cell velocities and lower IR-induced endothelial expression of intercellular adhesion molecule-1 in the synovial membrane might explain the greater resistance of this compartment to the inflammatory consequences of IR.

Topics: Animals; Carrageenan; Disease Models, Animal; Hindlimb; Intercellular Adhesion Molecule-1; Kaolin; Knee Joint; Male; Microcirculation; Neutrophils; Osteoarthritis, Knee; Periosteum; Rats; Rats, Wistar; Reperfusion Injury; Synovectomy; Synovial Membrane; Tibia; Xanthine Dehydrogenase

We have previously shown that lyophilized salmon thrombin and fibrinogen (STF) embedded in a dissolvable dextran dressing is as efficacious as Combat Gauze (CG) with regard to controlling hemorrhage and survival in non-coagulopathic swine with femoral artery lacerations. A major limitation of currently available advanced field dressings is the inability to control hemorrhage in coagulopathic casualties because of the exhaustion of host coagulation proteins. We tested the hypothesis that the STF dressing would be better able to control hemorrhage and prolong survival in coagulopathic swine compared to CG. Survival rate was 50% in CG-treated animals versus 90% in STF-treated animals. Survival time was significantly greater in STF-treated animals. Clots formed over the arterial injury in 100% of STF-treated animals compared to 0% in CG-treated animals (p < 0.001). STF-treated animals consumed less host coagulation factors, including platelets (p = 0.03). Survival after limb manipulation that simulated casualty evacuation was significantly higher with the STF dressing (p < 0.005). Angiographic observation of distal blood flow was seen twice as often with the STF dressing as with CG. The STF dressing allows a high survival rate, significantly greater survival time, and a significantly more stable dressing than CG in coagulopathic swine. The clot formed by the STF dressing also enables restoration of distal blood flow to the limb potentially resulting in higher limb salvage.

Topics: Animals; Bandages; Disease Models, Animal; Femoral Artery; Fibrinogen; Hemorrhage; Hemostatic Techniques; Kaolin; Salmon; Swine; Thrombin

Evidence-based guidelines do not indicate when ventricular reservoirs should be placed in children with neonatal hydrocephalus, and delayed intervention is common. We hypothesize that delayed ventricular drainage has adverse effects on structural development and functional outcomes.. Using a well-established animal model of kaolin-induced obstructive hydrocephalus, we evaluated neurologic deficit after early (~1 week post-kaolin) or late (~2 weeks post-kaolin) placement of ventricular reservoirs which were tapped according to strict neurologic criteria.. Progressive ventriculomegaly was similar in early- and late-reservoir implantation groups. The average neurologic deficit scores (NDSs) over the experimental period were 0 (n=6), 2.74 (n=5), and 2.01 (n=3) for the control, early-, and late-reservoir groups, respectively. At reservoir placement, early-group animals displayed enlarged ventricles without neurologic deficits (mean NDS=0.17), while the late group displayed ventriculomegaly with clinical signs of hydrocephalus (mean NDS=3.13). The correlation between ventriculomegaly severity and NDS in the early group was strongly positive in the acute (before surgery to 3 weeks post-reservoir placement) (R(2)=0.65) and chronic (6 to 12 weeks post-reservoir placement) (R(2)=0.65) phases, while the late group was less correlated (acute R(2)=0.51; chronic R(2)=0.19).. Current practice favors delaying reservoir implantation until signs of elevated intracranial pressure and neurologic deficit appear. Our results demonstrate that animals in early and late groups undergo the same course of ventriculomegaly. The findings also show that tapping reservoirs in these neonatal hydrocephalic animals based on neurologic deficit does not halt progressive ventricular enlargement and that neurologic deficit correlates strongly with ventricular enlargement.

Topics: Animals; Animals, Newborn; Cats; Cerebral Ventricles; Disease Models, Animal; Drainage; Hydrocephalus; Kaolin; Linear Models; Magnetic Resonance Imaging; Motor Skills; Nervous System Diseases; Neurologic Examination; Time Factors

The mechanisms of hydrocephalus formation remain unclear.. To measure intracranial biomechanical changes in rats with hydrocephalus.. Stress-strain relationships were determined by using force-controlled indentation through a craniotomy. Cortical blood flow and intracerebral pressures were monitored. In normal rats, deformability of intracranial contents was examined by applying 100 (20-100 mN) indentation cycles and during a 2-hour stress (100 mN) holding test. Hydrocephalus was induced in 56-day rats by cisternal kaolin injection. Magnetic resonance imaging was used to measure ventricle size and cortical blood flow.. Application of a constant small force for 2 hours or 100 cycles of a small indentation caused progressive intracranial deformation. Following kaolin injection, the ventricles of 3- to 4-day, 7- to 9-day, and 12- to 15-day hydrocephalic rats progressively enlarged, the dorsal cerebrum thickness decreased by >40%, and cortical blood flow decreased by ∼20%. After 3 to 4 days, intracranial pressure and intraparenchymal pulse pressure increased significantly by ∼85%, and diminished thereafter. After 7 to 9 days, there was a transient significant increase of the intracranial stiffness (indentation modulus). Viscoelastic strain during application of a constant force significantly increased by >50% at 7 to 9 and 12 to 15 days.. The observation that very small forces applied exogenously or endogenously (through pulsatile brain micromotions) cause progressive intracranial deformation suggests that the brain behaves in a poroviscoelastic manner. Intracranial pulsatility is increased during the early phases of ventriculomegaly. Small viscoelastic property changes of the intracranial contents accompany the ventriculomegaly. Consolidation of brain tissue by the pulsatile forces likely occurs through displacement of intraparenchymal fluids.

Topics: Animals; Biomechanical Phenomena; Cerebral Cortex; Craniotomy; Disease Models, Animal; Hydrocephalus; Intracranial Pressure; Kaolin; Magnetic Resonance Imaging; Male; Rats; Rats, Sprague-Dawley; Regional Blood Flow; Wakefulness

Object Experimental data about the evolution of intracranial volume and pressure in cases of hydrocephalus are limited due to the lack of available monitoring techniques. In this study, the authors validate intracranial CSF volume measurements within the lateral ventricle, while simultaneously using impedance sensors and pressure transducers in hydrocephalic animals. Methods A volume sensor was fabricated and connected to a catheter that was used as a shunt to withdraw CSF. In vitro bench-top calibration experiments were created to provide data for the animal experiments and to validate the sensors. To validate the measurement technique in a physiological system, hydrocephalus was induced in weanling rats by kaolin injection into the cisterna magna. At 28 days after induction, the sensor was implanted into the lateral ventricles. After sealing the skull using dental cement, an acute CSF drainage/infusion protocol consisting of 4 sequential phases was performed with a pump. Implant location was confirmed via radiography using intraventricular iohexol contrast administration. Results Controlled CSF shunting in vivo with hydrocephalic rats resulted in precise and accurate sensor measurements (r = 0.98). Shunting resulted in a 17.3% maximum measurement error between measured volume and actual volume as assessed by a Bland-Altman plot. A secondary outcome confirmed that both ventricular volume and intracranial pressure decreased during CSF shunting and increased during infusion. Ventricular enlargement consistent with successful hydrocephalus induction was confirmed using imaging, as well as postmortem. These results indicate that volume monitoring is feasible for clinical cases of hydrocephalus. Conclusions This work marks a departure from traditional shunting systems currently used to treat hydrocephalus. The overall clinical application is to provide alternative monitoring and treatment options for patients. Future work includes development and testing of a chronic (long-term) volume monitoring system.

Topics: Animals; Calibration; Catheters; Cerebrospinal Fluid; Cisterna Magna; Dilatation, Pathologic; Disease Models, Animal; Electric Impedance; Equipment Design; Gels; Hydrocephalus; In Vitro Techniques; Injections; Intracranial Pressure; Kaolin; Lateral Ventricles; Monitoring, Physiologic; Rats; Reproducibility of Results; Sepharose

The present study aims at better establishing the alterations caused by the usual enlargement of brain ventricles in this structure.. Hydrocephalus was induced in 7-day-old Wistar rats by the injection of kaolin into the cisterna magna. Morphological studies were performed on the hippocampus 7, 14 and 21 days after injection. The total number of neurons in each hippocampus subarea as well as that of pyknotic neurons were counted. Then we calculated the pyknotic index (PI) by hippocampal subarea, taking into account the level of ventricular dilatation and time of induction of hydrocephalus.. PI was statistically larger in the CA1 subarea of the experimental group after 1 week of hydrocephalus induction as compared to the corresponding control as well as in animals that had developed mild hydrocephalus in groups G1, G2 and G3.. Hydrocephalus caused morphological alterations in the hippocampus, leading to important changes in its shape.

Topics: Animals; CA1 Region, Hippocampal; CA2 Region, Hippocampal; CA3 Region, Hippocampal; Cell Count; Cisterna Magna; Dentate Gyrus; Disease Models, Animal; Hippocampus; Hydrocephalus; Kaolin; Neurons; Rats; Rats, Wistar

Endogenous stem cells theoretically could replace lost tissue and repair deficits caused by syringes. In this study the authors quantitatively examined 1) whether neural progenitor cells exist in an adult rat model of posttraumatic syringomyelia (PTS); 2) and if so, how long an active population of progenitor cells can persist; 3) whether the cell population's location is associated with the syrinx; 4) the degree of differentiation of the progenitor cells; and 5) the phenotypic fate of the progenitor cells.. Wistar rats were divided into intact, sham-operated, and experimental syrinx groups. Animals in each group were equally subdivided according to 4 time points: 7, 14, 28, and 56 days post-syrinx induction. Rats in the experimental syrinx group underwent a C-7 and T-1 laminectomy and then received 0.5 μl of a 24-mg/ml quisqualic acid spinal cord injection at the C-8 level to mimic an excitotoxic injury with an initial cyst, and 10 μl of a 250-mg/ml kaolin injection into the subarachnoid space at the C-8 level to create arachnoiditis. The proliferation, distribution, and differentiation of endogenous progenitor cells were identified immunocytochemically.. The authors observed a 20-fold increase in progenitor cells excluding inflammatory cells in the 1st 2 weeks post-syrinx induction. The cells persisted for at least 56 days, and 80% of them were located in the gray matter along the border of cysts. They included neural multipotential progenitor cells, oligodendroglial progenitor cells, and astrocytes.. Data in this study provide evidence for proliferation, distribution, and differentiation of endogenous progenitor cells in a model of PTS in adult rats. These progenitor cells proliferate rapidly, extend for long periods, and are mainly located in the gray matter along the border of syringes. Neural multipotential progenitor cells are expected to be associated with reparative and regenerative mechanisms of PTS. Glial cells are involved in the formation of a glial scar barrier that surrounds the syrinx and may prevent cyst enlargement. The authors' findings suggest that neural progenitor cells play a protective role in PTS.

Topics: Animals; Astrocytes; Biomarkers; Cell Cycle; Cell Differentiation; Cell Proliferation; Disease Models, Animal; Ectodysplasins; Glial Fibrillary Acidic Protein; Kaolin; Ki-67 Antigen; Oligodendroglia; Quisqualic Acid; Rats; Rats, Wistar; Spinal Cord; Spinal Cord Injuries; Stem Cells; Syringomyelia

Topics: Animals; Astrocytes; Biomarkers; Cell Cycle; Cell Differentiation; Cell Proliferation; Disease Models, Animal; Ectodysplasins; Glial Fibrillary Acidic Protein; Humans; Kaolin; Ki-67 Antigen; Oligodendroglia; Quisqualic Acid; Rats; Rats, Wistar; Spinal Cord; Spinal Cord Injuries; Stem Cells; Syringomyelia

Xiao-Ban-Xia-Tang (XBXT), a traditional Chinese herbal medicine, has been used in China for more than 2000 years, and proved to be effective in various cases of vomiting in the clinic.. To investigate the inhibitive effect of XBXT on cisplatin-induced pica behaviour and its effective mechanism on obestatin, CCK and CGRP in the pica model of rat.. The inhibitive effect of XBXT was investigated in the pica model of rats induced by cisplatin (3mg kg(-1), i.p.) in 72h observation, the expression of obestatin in the area postrema and ileum was measured by immunohistochemistry and PCR, and the levels of CCK and CGRP in blood were measured by Elisa.. The weight of kaolin eaten in rats induced by cisplatin was significantly reduced by pretreatment with XBXT in a dose-dependent manner during the 0-24h and 24-72h periods (P<0.05). XBXT exhibited effective dose-dependent (P<0.05) inhibition on the increase of expression levels of obestatin in both the ileum and area postrema, and markedly suppressed the increase levels of CCK and CGRP in blood induced by cisplatin in a dose-dependent manner (P<0.05).. XBXT has good activity against cisplatin-induced eating kaolin in rats possibly by inhibiting central or peripheral increase of obestatin, or the levels of CCK and CGRP in blood.

Topics: Animals; Antiemetics; Antineoplastic Agents; Area Postrema; Calcitonin Gene-Related Peptide; Cholecystokinin; Cisplatin; Disease Models, Animal; Dose-Response Relationship, Drug; Down-Regulation; Drugs, Chinese Herbal; Female; Ghrelin; Ileum; Kaolin; Phytotherapy; Pica; Pinellia; Rats; Rats, Wistar; Zingiberaceae

To analyze the ventricular enlargement and myelination of the corpus callosum in adult dogs after four and eight weeks of kaolin-induction of hydrocephalus.. 36 dogs were randomly divided into 3 groups: 1 - without hydrocephalus, 2 - kaolin-induction of hydrocephalus until the fourth week, and 3 - kaolin-induction of hydrocephalus until the eighth week. Ventricular ratios and volumes were calculated using magnetic resonance images, and myelination of the corpus callosum were histologically evaluated using solocromo-cianin stain.. Radiological hydrocephalus was observed in 93.75% and overall mortality was 38.4%. Ventricular volumes and ratios were higher in groups 2 and 3 compared to group 1 and similar when measures in the fourth and eighth weeks were compared in the group 3. Indices of luminescence in the knee and in the splenium of the corpus callosum were higher in group 2 than in group 1 indicating that there was loss of myelin in group 2, and similar in groups 1 and 3, showing a tendency to remyelination after 8 weeks.. The corpus callosum of dogs with kaolin-induced hydrocephalus responds with demyelination of the knee and splenium by the fourth week with a tendency to remyelination by the eighth week.

Topics: Aluminum Silicates; Animals; Cerebral Ventricles; Corpus Callosum; Disease Models, Animal; Dogs; Female; Heart Ventricles; Hydrocephalus; Kaolin; Magnetic Resonance Imaging; Male; Myelin Sheath; Organ Size; Random Allocation; Reproducibility of Results; Time Factors

Topics: Animals; Disease Models, Animal; Drug Evaluation, Preclinical; Ear, Inner; Habituation, Psychophysiologic; Injections; Kaolin; Mice; Motion Sickness; Reproducibility of Results; Rotation; Vestibule, Labyrinth

Transcutaneous electrical nerve stimulation (TENS) is a treatment for pain that involves placement of electrical stimulation through the skin for pain relief. Previous work from our laboratory shows that repeated application of TENS produces analgesic tolerance by the fourth day and a concomitant cross-tolerance at spinal opioid receptors. Prior pharmacological studies show that blockade of cholecystokinin (CCK) receptors systemically and spinally prevents the development of analgesic tolerance to repeated doses of opioid agonists. We therefore hypothesized that systemic and intrathecal blockade of CCK receptors would prevent the development of analgesic tolerance to TENS, and cross-tolerance at spinal opioid receptors. In animals with knee joint inflammation (3% kaolin/carrageenan), high (100Hz) or low frequency (4Hz) TENS was applied daily and the mechanical withdrawal thresholds of the muscle and paw were examined. We tested thresholds before and after inflammation, and before and after TENS. Animals treated systemically, prior to TENS, with the CCK antagonist, proglumide, did not develop tolerance to repeated application of TENS on the fourth day. Spinal blockade of CCK-A or CCK-B receptors blocked the development of tolerance to high and low frequency TENS, respectively. In the same animals we show that spinal blockade of CCK-A receptors prevents cross-tolerance at spinal delta-opioid receptors that normally occurs with high frequency TENS; and blockade of CCK-B receptors prevents cross-tolerance at spinal mu-opioid receptors that normally occurs with low frequency TENS. Thus, we conclude that blockade of CCK receptors prevents the development of analgesic tolerance to repeated application of TENS in a frequency-dependent manner.

Topics: Analgesics, Opioid; Animals; Arthritis, Experimental; Benzamides; Biophysics; Carrageenan; Cholecystokinin; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Administration Routes; Drug Tolerance; Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; Hyperalgesia; Kaolin; Knee Joint; Male; Pain Measurement; Pain Threshold; Piperazines; Rats; Rats, Sprague-Dawley; Receptors, Cholecystokinin; Statistics, Nonparametric; Transcutaneous Electric Nerve Stimulation

AD pathology is often seen in cortical biopsies of NPH patients. It remains unclear whether these findings are coincidental or causally related. In an aged animal model of NPH, we quantify Abeta and pTau accumulation and describe its temporal and spatial distribution. One-year-old male Sprague-Dawley rats had hydrocephalus induced by cisternal kaolin injection. Immunohistochemistry (IMHC) for AbetaPP, Abeta40, Abeta42 and pTau (epitope pT231) and ELISA for Abeta40, Abeta42 and pT231 were performed on controls and after 2, 6 and 10 weeks of hydrocephalus. Rats had double-label fluorescence IMHC for localization of Abeta42 and pT231. IMHC showed no change in neuronal AbetaPP expression following hydrocephalus. Abeta42 appeared earliest in CSF clearance pathways, p<0.05, and also showed significant rises in perivascular spaces and in cortical parenchyma. Mean ELISA values for Abeta40 and Abeta42 increased three- to four-fold in hydrocephalic rats at 6 and 10 weeks. Abeta40 increased between 2 and 6 weeks (p=0.0001), and remained stable at 10 (p=0.0002); whereas Abeta42 was elevated at 2 weeks (p<0.04) and remained at 6 (p=0.015). PTau at 6 and 10 weeks showed AD-like increased neuronal somatic staining and loss of dendritic staining. ELISA demonstrated increased pT231 in hydrocephalic rats at 10 weeks (p<0.0002). Double-label fluorescence for Abeta42 and pT231 revealed intraneuronal co-localization. Hydrocephalus in the elderly rat, therefore, can induce both Abeta and pTau accumulation. As distinct from brain injury models, no increase in AbetaPP expression was demonstrated. Rather, altered CSF dynamics appears to impair Abeta clearance in this NPH model.

Topics: Aging; Amyloid beta-Peptides; Amyloid beta-Protein Precursor; Animals; Brain; Cerebral Cortex; Disease Models, Animal; Hippocampus; Hydrocephalus, Normal Pressure; Kaolin; Male; Neurons; Peptide Fragments; Phosphorylation; Rats; Rats, Sprague-Dawley; tau Proteins; Time Factors

In 2007, a potent procoagulant mineral called WoundStat (WS), consisting of smectite granules, received clearance from the Food and Drug Administration for marketing in the United States for temporary treatment of external hemorrhage. Previously, we found that microscopic WS particles remained in the injured vessels that were treated, despite seemingly adequate wound debridement. Thus, we investigated the thromboembolic risk of using WS when compared with kaolin-coated gauze, Combat Gauze (CG); or regular gauze, Kerlix (KX) to treat an external wound with vascular injuries in pigs.. The right common carotid artery and external jugular vein of pigs were isolated and sharply transected (50%). After 30 seconds of free bleeding, the neck wounds were packed with WS, CG, or KX and compressed until hemostasis was achieved (n = 8 per group). Wounds were debrided after 2 hours, and vascular injuries were primarily repaired with suture. Blood flow was restored after infusing 1 L of crystalloid (no heparin or aspirin) and the wounds were closed. Two hours later, computed tomographic angiography was performed, and the wounds were reopened to harvest the vessels. The brains and lungs were recovered for gross and microscopic examination after euthanasia.. No differences were found in baseline measurements. Thrombelastography showed similar hypercoagulability of the final blood samples when compared with baselines in all groups. All vessels treated with KX or CG were patent and had no thrombus or blood clot in their lumen. In contrast, seven of eight carotid arteries and six of eight jugular veins treated with WS developed large occlusive red thrombi and had no flow. Small clots and WS residues were also found in the lungs of two pigs. Histologically, significant endothelial and transmural damage was seen in WS-treated vessels with luminal thrombi and embedded WS residues.. WS granules caused endothelial injury and significant transmural damage to the vessels that render them nonviable for primary surgical repair. The granules can enter systemic circulation and cause distal thrombosis in vital organs. More relevant in vitro and in vivo safety tests should be required for clearance of new hemostatic agents.

Topics: Animals; Bandages; Carotid Artery Injuries; Carotid Artery, Common; Disease Models, Animal; Hemostatics; Jugular Veins; Kaolin; Male; Materials Testing; Radiography; Regional Blood Flow; Silicates; Swine; Thrombelastography

This study was designed to explore the effects of infliximab on the optic pathway in kaolin induced hydrocephalus rabbit model.. After injection of kaolin to the cisterna magna of 12 New Zealand rabbits for induction of hydrocephalus, animals were divided into 2 groups and received either infliximab or normal saline. The intracranial pressure measurement was performed 2 times; firstly, before kaolin injection and secondly, before decapitation to ensure that the rabbits had hydrocephalus. After 2 weeks, animals were decapitated.. Apoptotic cells in the lateral geniculate body, optic radiation, and optic disc were counted with TUNEL method. Apoptotic cell counts of the lateral geniculate body and the optic radiation were showed statistically significant difference between the infliximab group and the control group.. This study suggests that infliximab may have a neuroprotective effect through its anti-apoptotic property on hydrocephalus induced optic pathways injury.

Topics: Animals; Antibodies, Monoclonal; Apoptosis; Cell Count; Disease Models, Animal; Geniculate Bodies; Hydrocephalus; Infliximab; Intracranial Pressure; Kaolin; Male; Rabbits; Visual Pathways

Although hydrocephalus is usually considered a disorder of periventricular white matter, disturbance of gray matter is probably also involved. However, so far gray matter metabolism has not been studied in experimental hydrocephalus using high resolution in vivo magnetic resonance spectroscopy (MRS). Therefore 15 rats were made hydrocephalic by injection of 0.1 ml kaolin into the cisterna magna, whereas 10 sham-operated rats served as controls. (1)H MRS and magnetic resonance imaging were performed longitudinally in acute hydrocephalus 2 and 4 weeks after kaolin treatment and in chronic hydrocephalus after 6 weeks. Volumes of interest included the gray matter regions cortex, thalamus and hippocampus. In hydrocephalic animals, (1)H MRS revealed decreased glutamate levels in all examined areas at all time points. Moreover, in acute hydrocephalus disturbances were noted in the hippocampus with decreased concentrations of N-acetyl aspartate, creatine, inositol and taurine, and in the cortex with decreased taurine levels. A clear lactate peak was detected in CSF spectra from hydrocephalic rats. In addition, T2-weighted images showed increase of free water in the hippocampus. It can be concluded that glutamate metabolism is deranged in gray matter in acute and chronic hydrocephalus in rats. If confirmed in humans, early detection of glutamatergic disturbances and lactate accumulation using in vivo(1)H MRS might serve as an indication for surgical treatment of hydrocephalus before irreversible neuronal damage develops.

Topics: Analysis of Variance; Animals; Aspartic Acid; Brain; Brain Chemistry; Brain Mapping; Creatine; Disease Models, Animal; Glutamic Acid; Hydrocephalus; Image Processing, Computer-Assisted; Inositol; Kaolin; Lactic Acid; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Male; Rats; Rats, Sprague-Dawley; Time Factors; Tritium

In communicating hydrocephalus (CH), explanations for the symptoms and clear-cut effective treatments remain elusive. Pulsatile flow through the cerebral aqueduct is often significantly elevated, but a clear link between abnormal pulsations and ventriculomegaly has yet to be identified. We sought to demonstrate measurement of pulsatile aqueductal flow of CSF in the rat, and to characterize the temporal changes in CSF pulsations in a new model of CH. Hydrocephalus was induced by injection of kaolin into the basal cisterns of adult rats (n = 18). Ventricular volume and aqueductal pulsations were measured on a 9.4 T MRI over a one month period. Half of the animals developed ventricular dilation, with increased ventricular volume and pulsations as early as one day post-induction, and marked chronic elevations compared to intact controls (volume: 130.15 +/- 83.21 microl vs. 15.52 +/- 2.00 microl; pulsations: 114.51 nl +/- 106.29 vs. 0.72 +/- 0.13 nl). Similar to the clinical presentation, the relationship between ventricular size and pulsations was quite variable. However, the pulsation time-course revealed two distinct sub-types of hydrocephalic animals: those with markedly elevated pulsations which persisted over time, and those with mildly elevated pulsations which returned to near normal levels after one week. These groups were associated with severe and mild ventriculomegaly respectively. Thus, aqueductal flow can be measured in the rat using high-field MRI and basal cistern-induced CH is associated with an immediate change in CSF pulsatility. At the same time, our results highlight the complex nature of aqueductal pulsation and its relationship to ventricular dilation.

Topics: Analysis of Variance; Animals; Cerebral Aqueduct; Cerebral Ventricles; Dilatation, Pathologic; Disease Models, Animal; Female; Hydrocephalus; Imaging, Three-Dimensional; Kaolin; Magnetic Resonance Imaging; Pulsatile Flow; Rats; Rats, Sprague-Dawley; Time Factors

Hydrocephalus is a common neurological problem in humans, usually caused by an impairment of cerebrospinal fluid (CSF) flow or absorption. A reliable induced model of chronic hydrocephalus in mice would be useful to test hypotheses using genetic mutants. Our goal was to characterize behavioral and histological changes in juvenile and young adult mice with kaolin (aluminum silicate)-induced hydrocephalus. Seven-day old and 7-8 week old mice received injection of kaolin into the cisterna magna. Behavior was assessed repeatedly. Seven or 14 days following kaolin, magnetic resonance (MR) imaging was used to assess ventricle size. In hydrocephalic mice, body weight was significantly lower than in age-matched saline-injected sham controls and the gait and posture score were impaired. Juvenile mice developed severe ventriculomegaly and had reduced corpus callosum thickness with gross white matter destruction by 14 days. Reactive astroglial change in white matter and cortex and reduced cellular proliferation in the subependymal zone were also apparent. Young adult mice developed only moderate ventricular enlargement without overt white matter destruction, although there was corpus callosum atrophy and mild astroglial reaction in white matter. Glial fibrillary acidic protein content was significantly higher in juvenile and young adult hydrocephalic mice at 7 and 14 days, but myelin basic protein content was not significantly altered. In conclusion, hydrocephalus induced by percutaneous injection of kaolin in juvenile and young adult mice is feasible. The associated periventricular alterations are essentially the same as those reported in rats of comparable ages.

Topics: Aging; Animals; Animals, Newborn; Antidiarrheals; Astrocytes; Body Weight; Brain; Cerebral Cortex; Corpus Callosum; Disease Models, Animal; Glial Fibrillary Acidic Protein; Gliosis; Hydrocephalus; Injections, Intraventricular; Kaolin; Lateral Ventricles; Magnetic Resonance Imaging; Male; Mice

Anticancer agents, such as cisplatin, stimulate nausea, vomiting, and behaviors indicative of malaise. Rats and mice do not possess a vomiting response, and, therefore, in these species, the ingestion of kaolin clay (a pica response) has been used as an index of malaise. In the rat, cisplatin-induced kaolin intake is inhibited by antiemetic treatments. In addition, cisplatin activates vagal afferent fibers in the gut, and kaolin intake induced by cisplatin is largely dependent on an intact vagus. Nevertheless, little is known about the brain pathways controlling pica. We investigated the role of the lateral parabrachial nucleus (lPBN), a major visceral afferent link between the hindbrain and forebrain, in cisplatin-induced c-Fos expression and pica. Injection of cisplatin (6 mg/kg ip) produced c-Fos expression in the ventrolateral (external) lPBN, a region receiving viscerosensory input. In rats with bilateral ibotenic acid lPBN lesions, cisplatin treatment substantially increased kaolin intake compared with controls ( approximately 30 g vs. approximately 5 g, respectively, over 24 h). Food intake was reduced by cisplatin treatment and by apomorphine, an emetic agent that acts centrally. Unlike cisplatin, however, apomorphine stimulated kaolin intake to a similar degree in both the lesioned and control rats, suggesting that lPBN damage neither produces nonspecific effects nor enhances malaise in general. These data suggest that lPBN-lesioned animals not only demonstrate pica after cisplatin treatment, but, in fact, show an exaggerated response that is greatly in excess of any treatment known to produce kaolin intake in rats.

Topics: Animals; Antineoplastic Agents; Apomorphine; Behavior, Animal; Cisplatin; Disease Models, Animal; Eating; Emetics; Injections, Intraperitoneal; Kaolin; Male; Neurons, Afferent; Pica; Pons; Proto-Oncogene Proteins c-fos; Rats; Rats, Sprague-Dawley; Solitary Nucleus

The HemCon (HC) bandage and QuickClot have been used over the past 6 years for treating external compressible hemorrhage in combat casualties. Previously, we tested three new hemostatic agents in granular/powder forms that were superior to these products. In this study, four new dressings (preselected) that are more suitable for battlefield application were evaluated. The efficacy and acute safety of the dressings were tested in our standard arterial hemorrhage model.. Anesthetized pigs (n = 38, 37 kg) were instrumented, and arterial blood was collected for hematological and coagulation assays. After splenectomy, the right femoral artery was isolated, injured (6 mm arteriotomy), and unrestricted bleeding allowed for 45 seconds. A hemostatic dressing (HC RTS [n = 6], Celox-D [CXb, n = 6], TraumaStat [TS, n = 10], Combat Gauze [CG, n = 10], or placebo gauze [PG, n = 6]) was then applied over the wound randomly and compressed for 2 minutes. Fluid resuscitation was administered and titrated to maintain a mean arterial pressure of 65 mm Hg. Animals were observed for 180 minutes or until death. Computed tomography angiography was performed on survivors and tissues were collected for histology.. No differences were found in baseline blood measures, pretreatment blood loss or fluid infusion among groups. HCs and CXb testing discontinued after six unsuccessful tests, and the data were excluded. Stable hemostasis was achieved in two PG, two TS, and eight CG pigs in remaining groups resulting in stabilized mean arterial pressure and significantly different survival rates (20-80%, p = 0.03). CG secured hemostasis for 134.6 minutes +/- 22.2 minutes, which was significantly longer than TS (35.7 +/- 22.0 minutes, p < 0.05) but not different from PG (57.9 +/- 36.2 minutes). The average survival time of CG-treated animals (167.3 +/- 5.9 minutes) was also significantly longer (p < 0.05) than that of TS- (90.0 +/- 15.3 minutes) or PG-treated (121 +/- 19.3 minutes) pigs. Posttreatment blood loss was less in CG (37.4 +/- 17.3 mL/kg) than that of the two other groups (TS = 79.8 +/- 13.8 mL/kg and PG = 75.5 +/- 23.8 mL/kg), but this difference was not significant. No significant rise in wound temperature (>1 degrees C) was recorded after treatment with dressings and computed tomography images showed no flow through the vessels. Histologic observations showed mild to moderate changes in treated vessels with no difference between CG and PG. In vitro analysis of blood treated with CG or PG (lesser extent) showed increased clotting rate and clot strength. TS treatment had no effect on blood clotting activity.. CG was the most effective dressing tested in this arterial hemorrhage model. The hemostatic property of CG is attributed to its raw material (nonwoven Rayon and polyester blend), kaolin coating, and the large surface area (3 inch x 4 yd) of this absorbent sponge. CG is now recommended as the first line of treatment for life-threatening hemorrhage on the battlefield, replacing HC.

Topics: Animals; Biopolymers; Disease Models, Animal; Equipment Design; Femoral Artery; Hemorrhage; Hemostatics; Kaolin; Male; Occlusive Dressings; Pliability; Swine; Treatment Outcome; Wounds, Penetrating

Topics: Animal Welfare; Animals; Brain; Cats; Cerebral Ventricles; Cerebrospinal Fluid Pressure; Disease Models, Animal; Dose-Response Relationship, Drug; Female; Hydrocephalus; Kaolin; Ventriculostomy

The amygdala plays an important role in the emotional-affective component of pain and in pain modulation. Group III metabotropic glutamate receptors (mGluRs) regulate pain-related activity in the amygdala, but the behavioral consequence and contribution of individual subtypes are not known yet. This study determined the effects of mGluR7 and mGluR8 activation in the central nucleus of the amygdala (CeA) on nocifensive and affective pain responses and on pain-related anxiety-like behavior of adult rats. The pain state was induced by intraarticular injections of kaolin/carrageenan into one knee joint to produce a localized monoarthritis. Subtype-selective agonists were administered into the CeA by microdialysis in normal rats and in rats with arthritis. An mGluR7-selective agonist (N,N'-dibenzyhydryl-ethane-1,2-diamine dihydrochloride, AMN082, 25microM) decreased spinal withdrawal reflex thresholds and increased audible and ultrasonic vocalizations evoked by brief (15s) compression of the knee. AMN082 also decreased the open-arm preference in the elevated plus maze (EPM) test, suggesting anxiety-like behavior. In arthritic animals, however, AMN082 failed to modulate the increased spinal reflexes and vocalizations and anxiety-like behavior. An mGluR8-selective agonist (S-3,4-dicarboxyphenylglycine, S-3,4-DCPG, 10microM) had no effect in normal animals but inhibited the increased spinal reflex responses and audible and ultrasonic vocalizations of arthritic rats. S-3,4-DCPG also increased the open-arm choices of arthritic rats, suggesting anxiolytic effects. The results suggest that under normal conditions mGluR7, but not mGluR8, facilitates pain responses and has anxiogenic properties whereas mGluR8, but not mGluR7, can inhibit nocifensive and affective behaviors and anxiety in a model of arthritic pain.

Topics: Amygdala; Animals; Arthritis; Behavior, Animal; Benzhydryl Compounds; Benzoates; Disease Models, Animal; Excitatory Amino Acid Agonists; Glycine; Kaolin; Male; Maze Learning; Microdialysis; Pain; Pain Measurement; Pain Threshold; Physical Stimulation; Rats; Rats, Sprague-Dawley; Receptors, Metabotropic Glutamate; Reflex

Topics: Animals; Antineoplastic Agents; Carmine; Disease Models, Animal; Kaolin; Mice; Pica; Radiotherapy; Rats; Rats, Wistar; Vomiting

Although posttraumatic syringomyelia (PTS) develops in up to 30% of patients after spinal cord injury (SCI), the pathophysiology of this debilitating complication is incompletely understood. To provide greater insight into the mechanisms of this degenerative sequela of SCI, the authors developed and characterized a novel model of PTS.. The spinal cords of 64 female Wistar rats were injured by 35-g modified aneurysm clip compression at the level of T6-7. Kaolin (5 microl of 500 mg/ml solution) was then injected into the subarachnoid space rostral to the site of the injury to induce inflammatory arachnoiditis in 22 rats. Control groups received SCI alone (in 21 rats), kaolin injection alone (in 15 rats), or laminectomy and durotomy alone without injury (sham surgery in 6 rats).. The combination of SCI and subarachnoid kaolin injection resulted in a significantly greater syrinx formation and perilesional myelomalacia than SCI alone; SCI and kaolin injection significantly attenuated locomotor recovery and exacerbated neuropathic pain (mechanical allodynia) compared with SCI alone. We observed that combined SCI and kaolin injection significantly increased the number of terminal deoxytransferase-mediated deoxyuridine triphosphate nick-end labeled-positive cells at 7 days after injury (p<0.05 compared with SCI alone) and resulted in a significantly greater extent of astrogliosis and macrophage/microglial-associated inflammation at the lesion (p<0.05).. The combination of compressive/contusive SCI with induced arachnoiditis results in severe PTS and perilesional myelomalacia, which is associated with enhanced inflammation, astrogliosis, and apoptotic cell death. The development of delayed neurobehavioral deficits and neuropathic pain in this model accurately reflects the key pathological and clinical conditions of PTS in humans.

Topics: Animals; Arachnoiditis; Disease Models, Animal; Female; Kaolin; Rats; Rats, Wistar; Reproducibility of Results; Spinal Cord Injuries; Subarachnoid Space; Syringomyelia; Thoracic Vertebrae

Communicating hydrocephalus (CH) occurs frequently, but clinically-relevant animal models amenable to diagnostic imaging and cerebrospinal fluid shunting are not available. In order to develop and characterize models of subarachnoid space (SAS) obstruction at the basal cisterns (BC) or cerebral convexities (CX), 25% kaolin was injected in adult female Sprague-Dawley rats following halothane anesthesia; intact- or saline-injected animals served as controls. For BC animals (n=28 hydrocephalics, n=20 controls), an anterior approach to the C1-clivus interval was employed and 30 microl of kaolin or saline was injected. For CX injections (n=13 hydrocephalics, n=3 controls), 50-60 microl of kaolin was injected bilaterally after separating the partitions in the SAS. In BC-injected rats, kaolin was observed grossly in the basal cisterns but not in the cisterna magna or at the foramina of Luschka, indicating that communicating (or extra-ventricular)--not obstructive--hydrocephalus had been induced. Following ketamine/xylazine anesthesia, magnetic resonance imaging (MRI) of gadolinium injected into the lateral ventricle also demonstrated CSF flow from the foramina of Luschka. MRI also revealed that ventriculomegaly progressed steadily in BC animals and by 2 weeks post-kaolin the mean Evan's ratio (frontal horn) increased significantly (mean 0.45 compared to 0.31 in intact- and 0.34 in saline-injected controls; p<0.001 for each). CX animals exhibited kaolin deposits covering approximately 80% of the cerebral hemispheres and developed noticeable ventriculomegaly (mean Evan's ratio 0.40), which was significant relative to intact animals (p=0.011) but not saline-injected controls. Surprisingly, ventriculomegaly following CX injections was less severe and much more protracted, requiring 3-4 months to develop compared to ventriculomegaly produced by BC obstruction. No hydrocephalic animals demonstrated obvious neurological deficits, but BC-injected animals that subsequently developed more severe ventriculomegaly exhibited nasal discharges and "coughing" for several days following kaolin injection. The new BC model is relevant because the clinical presentation of CH in children is often associated with obstruction at this site, while the CX model may be more representative of late adult onset normal pressure hydrocephalus.

Topics: Age Factors; Animals; Cerebral Cortex; Cisterna Magna; Disease Models, Animal; Female; Humans; Hydrocephalus; Kaolin; Radiography; Rats; Rats, Sprague-Dawley; Subarachnoid Space

Nociceptive impulse activity was recorded extracellularly from single A delta and C primary afferents of the guinea pig's medial articular nerve after induction of an experimental osteoarthritis in the knee joint by partial medial menisectomy and transection of the anterior cruciate ligament (PMM+TACL). Also, the analgesic effects of intra-articular hyaluronan solutions were evaluated. Healthy, PMM+TACL operated, sham-operated (opening of the joint capsule without PMM and TACL surgery) and acutely inflamed (intra-articular kaolin-carrageenan, K-C) animals were used. The stimulus protocol consisted of torque meter-controlled, standardized innocuous and noxious inward and outward rotations of the joint. This stimulus protocol of 50 s duration was repeated every 5 min for 70 min. One day, one week and three weeks after PMM+TACL, the movement-evoked discharges of A delta articular afferents were increased significantly over values found in sham-operated animals. The discharges of C fibers were significantly augmented only one week after PMM+TACL surgery. Filling of the joint cavity with a high viscosity hyaluronan solution (hylan G-F 20, Synvisc) immediately and three days after surgery reduced significantly the enhanced nerve activity observed in joint afferent fibers one day and one week after surgery. Augmentation of movement-evoked discharges in K-C acutely inflamed knee joints was similar to that observed one week after PMM+TACL. Our results indicate that in the PMM+TACL model of osteoarthritis in guinea pigs, enhancement of nociceptive responses to joint movement was primarily associated to post-surgical inflammation. Intra-articular injection of an elastoviscous hyaluronan solution reduced the augmented nerve activity.

Topics: Adjuvants, Immunologic; Animals; Anterior Cruciate Ligament; Carrageenan; Disease Models, Animal; Evoked Potentials, Motor; Female; Guinea Pigs; Hyaluronic Acid; Injections, Intra-Articular; Joint Instability; Kaolin; Knee Joint; Male; Menisci, Tibial; Movement; Neural Conduction; Nociceptors; Osteoarthritis, Knee; Pain; Solutions

Spinal drainage of cerebrospinal fluid (CSF) into the lymphatic system is important in physiological and pathological conditions in both humans and rodents. However, in hydrocephalus and syringomyelia the exact CSF pathway from the central canal into the lymphatic tissue around the spinal nerves remains obscure. We therefore induced syringomyelia and hydrocephalus in 36 Lewis rats by injection of 0.1 ml kaolin into the cisterna magna. At 2, 4 and 6 weeks later cationized ferritin was stereotactically infused into the cisterna magna of controls and into the lateral ventricles of hydrocephalic animals followed by dissection of brain, spinal cord and spinal nerves. CSF pathway and tracer flow were studied by light and electron microscopy. We found that in rats with kaolin-induced CSF outflow obstruction, CSF passes from central canal syringes through ruptured ependyma and dorsal columns into the spinal subarachnoid space, from where it is absorbed along spinal nerves into extradural lymphatic vessels. Taken into account that spinal hydrostatic pressure in humans differs significantly from pressure in animals due to the upright gait, we conclude that spinal compensatory CSF outflow pathways might be of even greater importance in human hydrocephalus.

Topics: Analysis of Variance; Animals; Brain; Cerebrospinal Fluid; Disease Models, Animal; Ferritins; Hydrocephalus; Kaolin; Microscopy, Electron, Transmission; Rats; Rats, Inbred Lew; Spinal Cord; Spinal Nerves; Time Factors

Juvenile rats with kaolin-induced hydrocephalus have reduced brain injury if treated with nimodipine or magnesium sulfate. Experiments were conducted to determine if the neuroprotective effects could be replicated in neonatal rats with experimental hydrocephalus at an age comparable to prematurely born humans. In a blinded and randomized manner, drugs were administered for 14 days beginning 7 days after induction of hydrocephalus. Nimodipine was given twice daily by subcutaneous injections. Daily doses greater than 38 mg/kg of body weight were fatal. Daily doses of 3.8 to 30 mg/kg were not associated with behavioral, structural, or biochemical improvements. Magnesium chloride was administered via daily subcutaneous minipump infusion (0.87 or 1.74 mM/kg) along with twice daily injections of 0.74 or 1.48 mM/kg. Magnesium sulfate was administered by twice daily subcutaneous doses of 1.54 or 7.72 mM/kg. Sedation occurred, but there was no statistically significant protection in regard to behavior, brain structure, or brain composition in any of the magnesium experiments. Developmental alterations in calcium channels of the neonatal rat brain could account for differences from prior experiments in young hydrocephalic rats.

Topics: Animals; Animals, Newborn; Brain; Brain Damage, Chronic; Calcium Channel Blockers; Calcium Channels; Disease Models, Animal; Dose-Response Relationship, Drug; Female; Hydrocephalus; Infusion Pumps; Kaolin; Lateral Ventricles; Magnesium Chloride; Magnesium Compounds; Magnesium Sulfate; Male; Nerve Fibers, Myelinated; Neuroprotective Agents; Nimodipine; Rats; Rats, Sprague-Dawley; Survival Rate; Treatment Outcome

Ritonavir, a protease inhibitor drug, is commonly used in AIDS therapy. As with other chemotherapeutic drugs that cause gastrointestinal adverse effects, ritonavir treatment is associated with significant nausea and vomiting. This study investigated whether Scutellaria baicalensis, and its active flavonoid constituent, baicalein, attenuate the gastrointestinal effects of ritonavir. The effects of herb administration were evaluated in ritonavir-treated rats using a rat pica model, which simulates nausea and vomiting in humans. The effects of herb administration on gastric emptying in rats were also measured. Ritonavir treatment resulted in increased kaolin intake or severe pica, the intensity of which was reduced significantly with S. baicalensis administration (1 mg kg(-1); P<0.05). High-performance liquid chromatography analysis of S. baicalensis showed the presence of an extremely potent flavonoid constituent, baicalein. The study aimed to determine if baicalein contributed to the anti-pica effect of the extract. It was observed that baicalein dose-dependently decreased pica in ritonavir-treated rats (P<0.001). In addition to inducing pica, ritonavir also significantly delayed gastric emptying, which could contribute to ritonavir-induced gastrointestinal dysfunction. When S. baicalensis extract was administered to ritonavir-treated rats the delayed gastric emptying was significantly attenuated (P<0.05). The results suggest that S. baicalensis and the constituent baicalein reduce the gastrointestinal dysfunction caused by ritonavir. It is concluded that S. baicalensis may potentially have a role to play in reducing drug-induced adverse effects.

Topics: Animals; Antiemetics; Antioxidants; Disease Models, Animal; Dose-Response Relationship, Drug; Flavanones; Flavonoids; Gastric Emptying; HIV Protease Inhibitors; Kaolin; Male; Nausea; Pica; Plant Extracts; Plant Roots; Rats; Rats, Wistar; Ritonavir; Scutellaria baicalensis; Vomiting

Hydrocephalus is caused by an imbalance in cerebrospinal fluid (CSF) production and absorption, resulting in excess ventricular fluid accumulation and neurologic impairment. Current therapy for hydrocephalus involves surgical diversion of excess ventricular fluid. The water-transporting protein aquaporin-4 (AQP4) is expressed at the brain-CSF and blood-brain barriers. Here, we provide evidence for AQP4-facilitated CSF absorption in hydrocephalus by a transparenchymal pathway into the cerebral vasculature. A mouse model of obstructive hydrocephalus was created by injecting kaolin (2.5 mg/mouse) into the cisterna magna. Intracranial pressure (ICP) was approximately 5 mm Hg and ventricular size <0.3 mm(3) in control mice. Lateral ventricle volume increased to 3.7+/-0.5 and 5.1+/-0.5 mm(3) in AQP4 null mice at 3 and 5 days after injection, respectively, significantly greater than 2.6+/-0.3 and 3.5+/-0.5 mm(3) in wildtype mice (P<0.005). The corresponding ICP was 22+/-2 mm Hg at 3 days in AQP4 null mice, significantly greater than 14+/-1 mm Hg in wildtype mice (P<0.005). Brain parenchymal water content increased by 2% to 3% by 3 days, corresponding to approximately 50 muL of fluid, indicating backflow of CSF from the ventricle into the parenchymal extracellular space. A multi-compartment model of hydrocephalus based on experimental data from wildtype mice accurately reproduced the greater severity of hydrocephalus in AQP4 null mice, and predicted a much reduced severity if AQP4 expression/function were increased. Our results indicate a significant role for AQP4-mediated transparenchymal CSF absorption in hydrocephalus and provide a rational basis for evaluation of AQP4 induction as a nonsurgical therapy for hydrocephalus.

Topics: Animals; Antidiarrheals; Aquaporin 4; Blood-Brain Barrier; Cerebral Ventricles; Disease Models, Animal; Disease Progression; Humans; Hydrocephalus; Intracranial Pressure; Kaolin; Mice; Mice, Knockout; Water-Electrolyte Balance

We investigated how neural function is preserved or matured in the visual cortex of cats, following the induction of hydrocephalus by kaolin injection. In vivo optical imaging of intrinsic signals in 11-17-week-old hydrocephalic cats revealed orientation maps showing the orderly arrangement of preferred orientations when stimulated by grating stimuli at a low spatial frequency, whereas stimulus-evoked intrinsic signals in response to gratings at a high spatial frequency were often too weak to construct orientation maps. Furthermore, in two of the three hydrocephalic cats, initially deteriorated orientation maps became almost regular maps in the second imaging experiments conducted 8 and 11 weeks, respectively, after the first imaging. This indicates that, despite large structural deformation of the hydrocephalic brain, orientation maps are elaborated sufficiently after the age of 5-6 months, by which time the orientation map formation is usually completed in normal cats. Single unit recording from the decompressed visual cortex revealed that many neurons showed normal orientation selectivity, whereas the binocularity of these neurons was found to be reduced. These results suggested that the deformed visual cortex of hydrocephalic cats exhibits a high plasticity, retaining its functional organization.

Topics: Action Potentials; Animals; Brain Mapping; Cats; Diagnostic Imaging; Disease Models, Animal; Functional Laterality; Hydrocephalus; Kaolin; Orientation; Photic Stimulation; Time Factors; Vision, Ocular; Visual Cortex; Visual Pathways

Animal experimental study.. To study the origin of macrophages in a rat model of syringomyelia.. Syringomyelia is a clinically important condition in which a cystic cavity forms within the spinal cord. This leads to significant delayed neurologic deterioration, which may be manifested as weakness, numbness, or pain. The pathophysiology and mechanism of syrinx formation remain unclear. Human autopsy findings have demonstrated a prominent accumulation of macrophages in relation to the syrinx. Similar observations have also been made in a previously established rat model of syringomyelia. Little is known about the origin and precise functions of these cells.. Syrinx formation was induced by intraparenchymal injections of kaolin within the cervical spinal cords of 30 DA rat (RT7.1) radiation bone marrow chimeras reconstituted with bone marrow from RT7.2 congeneic donors. The distribution of macrophages was evaluated at survival times of 3 days, 1 week, and 4 weeks. Immunostaining of fresh-frozen spinal cord tissue was performed using specific antibodies against rat macrophage ED1 antigen and RT7.2 allele of CD45. This allowed donor-derived hematogenous (ED1+, RT7.2+) macrophages to be distinguished from native cells (ED1+, RT7.2-).. Central canal dilatation was seen from 1 week. This was associated with extensive accumulation of ED1+ macrophages within the spinal cord parenchyma. A large influx of bone marrow-derived (ED1+, RT7.2+) macrophages was observed. However, a considerable proportion of resident microglia (RT7.2-) also upregulated ED1. These activated microglia demonstrated distinct morphologic features.. Large numbers of macrophages were recruited from the bone marrow in kaolin-induced rat syringomyelia. However, a significant number of resident microglia upregulated their ED1 activity and appear to provide a substantial source of macrophages.

Topics: Animals; Bone Marrow; Cell Movement; Disease Models, Animal; Ectodysplasins; Injections, Spinal; Kaolin; Macrophages; Membrane Proteins; Microglia; Radiation Chimera; Rats; Rats, Inbred Strains; Specific Pathogen-Free Organisms; Spinal Cord; Syringomyelia; Tumor Necrosis Factors; Up-Regulation

The behavioral assessment of experimental pain is essential for the analysis of pain mechanisms and the validation of therapeutic targets. Arthritic pain, in particular, is significantly associated with negative affective states and disorders. Here we present a standardized method for the quantitative analysis of audible and ultrasonic (25 +/- 4 kHz) vocalizations in awake rats as a measure of higher integrated behavior in a model of arthritic pain. A bat detector and a condenser microphone were used to record ultrasonic and audible vocalizations, respectively, in response to innocuous and noxious mechanical stimulation of the knee before and after induction of acute arthritis in one knee. A computerized system was used to analyze number and duration of the filtered signals. For the behavioral tests, the animal was placed in a customized recording chamber to ensure consistent stimulus application and stable recordings and to eliminate any movement-induced noise. Noxious stimuli produced stronger vocalizations than innocuous stimuli. Both audible and ultrasonic vocalizations to innocuous (allodynia) and noxious (hyperalgesia) stimuli increased after the induction of acute arthritis. These changes were accompanied by increased knee joint circumference, lowered hind limb withdrawal thresholds and reduced exploratory behavior in the same animals. The computerized analysis of audible and ultrasonic vocalizations is a valid, quantitative, reliable and convenient method to measure pain-related behavior.

Topics: Analysis of Variance; Animals; Arthritis, Experimental; Behavior, Animal; Carrageenan; Disease Models, Animal; Exploratory Behavior; Kaolin; Knee Joint; Male; Numerical Analysis, Computer-Assisted; Pain; Pain Measurement; Physical Stimulation; Rats; Rats, Sprague-Dawley; Reaction Time; Time Factors; Ultrasonics; Vocalization, Animal; Weights and Measures

Mechanisms of pain-related plasticity in the amygdala, a key player in emotionality, were studied at the cellular and molecular levels in a model of arthritic pain. The influence of the arthritis pain state induced in vivo on synaptic transmission and N-methyl-d-aspartate (NMDA) receptor function was examined in vitro using whole-cell voltage-clamp recordings of neurones in the latero-capsular part of the central nucleus of the amygdala (CeA), which is now defined as the 'nociceptive amygdala'. Synaptic transmission was evoked by electrical stimulation of afferents from the pontine parabrachial area (part of the spino-parabrachio-amygdaloid pain pathway) in brain slices from control rats and from arthritic rats. This study shows that pain-related synaptic plasticity is accompanied by protein kinase A (PKA)-mediated enhanced NMDA-receptor function and increased phosphorylation of NMDA-receptor 1 (NR1) subunits. Synaptic plasticity in the arthritis pain model, but not normal synaptic transmission in control neurones, was inhibited by a selective NMDA receptor antagonist. Accordingly, an NMDA receptor-mediated synaptic component was recorded in neurones from arthritic animals, but not in control neurones, and was blocked by inhibition of PKA but not protein kinase C (PKC). Exogenous NMDA evoked a larger inward current in neurones from arthritic animals than in control neurones, indicating a postsynaptic effect. Paired-pulse facilitation, a measure of presynaptic mechanisms, was not affected by an NMDA-receptor antagonist. Increased levels of phosphorylated NR1 protein, but not of total NR1, were measured in the CeA of arthritic rats compared to controls. Our results suggest that pain-related synaptic plasticity in the amygdala involves a critical switch of postsynaptic NMDA receptor function through PKA-dependent NR1 phosphorylation.

Topics: Amygdala; Animals; Arthralgia; Arthritis, Experimental; Cyclic AMP-Dependent Protein Kinases; Disease Models, Animal; Kaolin; Neuronal Plasticity; Neurons; Phosphorylation; Rats; Rats, Sprague-Dawley; Receptors, N-Methyl-D-Aspartate; Synaptic Transmission

Cisplatin, a chemotherapeutic agent, causes significant nausea and vomiting. It is postulated that cisplatin-induced oxidant stress may be responsible for these symptoms. We tested whether pretreatment with American ginseng berry extract (AGBE), an herb with potent antioxidant capacity, and one of its active antioxidant constituents, ginsenoside Re, could counter cisplatin-induced emesis using a rat pica model.. In rats, exposure to emetic stimuli such as cisplatin causes significant kaolin intake, a phenomenon called pica. We therefore measured cisplatin-induced kaolin intake as an indicator of the emetic response. Rats were pretreated with vehicle, AGBE (dose range 50-150 mg/kg, IP) or ginsenoside Re (2 and 5 mg/kg, IP). Rats were treated with cisplatin (3 mg/kg, IP) 30 min later. Kaolin intake, food intake, and body weight were measured every 24 h for 120 h. Additionally, the free radical scavenging activity of AGBE was measured in vitro using ESR spectroscopy.. A significant dose-response relationship was observed between increasing doses of pretreatment with AGBE and reduction in cisplatin-induced pica. Kaolin intake was maximally attenuated by AGBE at a dose of 100 mg/kg. Food intake also improved significantly at this dose (P<0.05). Pretreatment with ginsenoside Re (5 mg/kg) also decreased kaolin intake (P<0.05). In vitro studies demonstrated a concentration-response relationship between AGBE and its ability to scavenge superoxide and hydroxyl radicals.. Pretreatment with AGBE and its major constituent, Re, attenuated cisplatin-induced pica, and demonstrated potential for the treatment of chemotherapy-induced nausea and vomiting. Significant recovery of food intake further strengthens the conclusion that AGBE may exert an antinausea/antiemetic effect.

Topics: Animals; Antidiarrheals; Antineoplastic Agents; Antioxidants; Cisplatin; Disease Models, Animal; Ginsenosides; Kaolin; Male; Oxidative Stress; Panax; Pica; Plant Extracts; Rats; Rats, Wistar; Vomiting

Rats lack the emetic reflex but exhibit pica in response to stimuli that induce emesis in species with an emetic reflex, hence it has been proposed that pica may be analogous to emesis in species lacking the reflex. In the present study, we investigated whether pica was present in Suncus murinus (with an emetic reflex) as well as in rats and mice (without emetic reflex) to provide a further insight to the validity of pica as a model for nausea/vomiting. Cisplatin (6 mg/kg, i.p.) induced pica in rats, indicated by a significant increase in kaolin consumption at 24 h (but not 48 h) post-treatment whereas we failed to demonstrate this effect in mice (inbred or outbred strain, 6 or 20 mg/kg i.p.) and whilst cisplatin (20 mg/kg, i.p.) induced emesis in Suncus, kaolin intake was not significantly affected. Furthermore, cisplatin significantly increased the weight of gastric contents at 48 h post-injection in rats and mice indicating delayed gastric emptying whereas this effect was not present in Suncus. These results show that Suncus and two strains of mice, unlike rats, do not develop pica in response to cisplatin which suggests that the consumption of kaolin induced by cisplatin may not be associated with whether or not an emetic reflex is present. The differences in ingestive behaviour and gastric response between species with and without an emetic reflex in response to cisplatin treatment as well as the difference between mice and rats, is discussed in relation to the selection of models for the study of nausea and vomiting.

Topics: Animals; Body Weight; Cisplatin; Disease Models, Animal; Drinking; Eating; Kaolin; Male; Mice; Nausea; Organ Size; Pica; Rats; Shrews; Species Specificity; Stomach; Time Factors

In laboratory animals many models of inflammation have been developed for preclinical evaluation of the pharmacological profiles of nonsteroidal anti-inflammatory drugs (NSAIDs). In contrast, in species of veterinary interest, including the cat, NSAIDs have been studied mainly using dose-titration or dose-confirmation studies in clinical subjects. This is due to the scarcity of appropriate animal models and to the associated lack of quantitative validated endpoints describing the magnitude and time course of drug response. Determination of pharmacokinetic/pharmacodynamic (PK/PD) relationships provides a powerful approach for the selection of effective and safe dosage regimens. In this study, a paw inflammation model in the cat was developed for the preclinical evaluation of NSAIDs using PK/PD modelling. Subcutaneous injection of 500 mg kaolin in the paw produced a well-defined and reproducible inflammatory response that lasted 4-5 days. Several endpoints were assessed for their clinical relevance and for their metrological performance (accuracy and reproducibility). Body temperature, lameness scoring, locomotion tests and possibly skin temperature were the most appropriate endpoints for testing the antipyretic, analgesic and anti-inflammatory effects of NSAIDs in the cat.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Cat Diseases; Cats; Disease Models, Animal; Female; Inflammation; Injections, Subcutaneous; Kaolin; Lameness, Animal; Male; Pain Measurement; Reproducibility of Results

To assess the specification and efficiency of rotation sickness indices by monitoring changes of behaviors in rats under rotation stimulation.. SD rats were stimulated by Crampton model with different time courses. Pica or kaolin consumption (KC), conditioned taste aversion (CTA) or saccharine water ingestion (SWI), 2 h food ingestion (2hFI), and open-field test (OFT) scores were observed.. Apparent changes of the four indices were observed after rotation stimulation. SWI, OFT scores and 2hFI decreased exponentially with increase of duration of the motion stimulation. KC increased linearly with the increase of time within 12 h stimulation. After 18 h stimulation, KC decreased to a level even lower than that after 6 or 12 h stimulation. The adjusted correlation between changes of the indices and duration of stimulation within 12 h are: 0.94 for KC, 0.54 for SWI, 0.44 for 2hFI and 0.34 for OFT. The maximum efficiency of the four indices appeared at 6-hour stimulation: 70% for KC, 90% for SWI, 80% for 2hFI and 95% for OFT.. It is found that pica and CTA were more specific than the other indices. They may serve as primary indices and can be combined with the secondary indices such as 2hFI or OFT. Six hours is the optimal duration of stimulation by Crampton model for rotation sickness studies.

Topics: Animals; Aversive Therapy; Behavior, Animal; Disease Models, Animal; Eating; Kaolin; Motion Sickness; Pica; Rats; Rats, Sprague-Dawley; Rotation; Saccharin; Taste; Time Factors; Water; Weightlessness Simulation

The goal of this investigation was to establish whether pressure gradients exist between the ventricles, brain tissue, and subarachnoid space when acute or chronic hydrocephalus develops. Such gradients are hypothesized by many models of hydrocephalus, but considerable controversy continues about their existence.. A stereotactic frame was used for surgery in dogs to implant pressure sensors within the right lateral ventricle, the frontal lobe, and forward in the subarachnoid space. The dogs were allowed to recover for 10 to 14 days postoperatively. Then, 800 mg of sterile kaolin in water was injected into the cisterna magna region by using a percutaneous approach. Both real-time and long-term intracranial pressures were measured. Of the six dogs, one experienced an intracranial hemorrhage, one dog displayed status epilepticus after a second injection of kaolin and was killed, one experienced acute hydrocephalus, and three experienced mild chronic hydrocephalus. No consistent pressure differences were found in any dog between the ventricle, brain, and subarachnoid space before kaolin administration or afterward when hydrocephalus developed. In addition, no pulse pressure gradients occurred between the brain and the ventricle or subarachnoid space.. Precise monitoring of pressure before and during the development of hydrocephalus did not detect pressure gradients between the ventricle, brain, and subarachnoid space. This was true for long-term measurements over weeks and for real-time measurements that allowed accurate assessment of pulse pressures. Theories predicting pressure gradients greater than the resolution of these sensors (0.5 mm Hg) across brain tissue have to be reevaluated in light of these findings.

Topics: Acute Disease; Animals; Blood Pressure; Cerebral Ventricles; Chronic Disease; Disease Models, Animal; Dogs; Hydrocephalus; Intracranial Pressure; Kaolin; Monitoring, Physiologic; Subarachnoid Space

To experimentally clarify the symptomatological and pathophysiological aspects of a newly proposed clinical entity, we produced an experimental rat "hydrocephalus-parkinsonism complex" model.. A total of 60 male Sprague-Dawley rats were used. Twenty rats were treated with only kaolin as controls. Hemiparkinsonism was induced in the other 40 rats by stereotactic injection of 6-hydroxydopamine (6-OHDA) directly into the right substantia nigra. Twenty of these 40 rats were then treated with an injection of kaolin into the cisterna magna 3 days after the induction of parkinsonism. Neurological features were assessed weekly for 1 to 6 weeks after 6-OHDA injection by an apomorphine-induced turning test.. The mortality rate was 25% in the rats injected with kaolin and 10% in those with the 6-OHDA injection. The frequency of the induction of parkinsonism-like signs was minimal in the first 2 weeks and reached a maximum point 4 weeks after the 6-OHDA injection. In contrast, the rats injected with both 6-OHDA and kaolin developed hemiparkinsonism-like signs in the early stage of the progression of hydrocephalus, and the peak incidence was reached in the 2nd week after induction ( p<0.05 compared with the 6-OHDA group). The severity of the neurological disturbance was also significantly more prominent in the latter group.. These results suggest that the hydrodynamic effect in the early period of ventriculomegaly is the mechanism for signs of parkinsonism in 6-OHDA-treated rats. It could be concluded that the hydrocephalic state aggravates parkinsonism, if any as the associated condition, and it may be a new clinical entity of hydrocephalus symptomatology with a specific pathophysiology.

Topics: Animals; Antiparkinson Agents; Apomorphine; Basal Ganglia Diseases; Behavior, Animal; Disease Models, Animal; Drug Interactions; Functional Laterality; Hydrocephalus; Kaolin; Male; Oxidopamine; Parkinsonian Disorders; Rats; Rats, Sprague-Dawley; Rotation; Substantia Nigra; Time Factors

Response properties of nociceptors in the temporomandibular joint (TMJ) and surrounding area under experimental inflammation were investigated using an in vitro TMJ-nerve preparation in the rat. Nociceptive units (receptor and innervating nerve fiber) were classified into the following subtypes: Adelta-high-threshold mechanonociceptor (HTM), Adelta-polymodal nociceptor (POLY), C-HTM and C-POLY. In the inflamed joint, mechanical thresholds tended to be lower; however, the reaction to bradykinin was not identified as clearly as in control. Experimentally induced inflammation increased the proportion of heat-sensitive units and lowered heat threshold significantly. These results suggest that inflammation may sensitize nociceptors in the temporomandibular joint, and cause hyperalgesia and allodynia.

Topics: Action Potentials; Animals; Arthralgia; Arthritis; Bradykinin; Carrageenan; Disease Models, Animal; Hyperalgesia; Kaolin; Mechanoreceptors; Nerve Fibers, Myelinated; Nerve Fibers, Unmyelinated; Nociceptors; Pain Threshold; Physical Stimulation; Rats; Rats, Wistar; Sensory Receptor Cells; Temporomandibular Joint; Temporomandibular Joint Disorders

Inflammatory pain is caused by sensitization of peripheral and central nociceptive neurons. Prostaglandins substantially contribute to neuronal sensitization at both sites. Prostaglandin E2 (PGE2) applied to the spinal cord causes neuronal hyperexcitability similar to peripheral inflammation. Because PGE2 can act through EP1-EP4 receptors, we addressed the role of these receptors in the spinal cord on the development of spinal hyperexcitability. Recordings were made from nociceptive dorsal horn neurons with main input from the knee joint, and responses of the neurons to noxious and innocuous stimulation of the knee, ankle, and paw were studied after spinal application of recently developed specific EP1-EP4 receptor agonists. Under normal conditions, spinal application of agonists at EP1, EP2, and EP4 receptors induced spinal hyperexcitability similar to PGE2. Interestingly, the effect of spinal EP receptor activation changed during joint inflammation. When the knee joint had been inflamed 7-11 hr before the recordings, only activation of the EP1 receptor caused additional facilitation, whereas spinal application of EP2 and EP4 receptor agonists had no effect. Additionally, an EP3alpha receptor agonist reduced responses to mechanical stimulation. The latter also attenuated spinal hyperexcitability induced by spinal PGE2. In isolated DRG neurons, the EP3alpha agonist reduced the facilitatory effect of PGE2 on TTX-resistant sodium currents. Thus pronociceptive effects of spinal PGE2 can be limited, particularly under inflammatory conditions, through activation of an inhibitory splice variant of the EP3 receptor. The latter might be an interesting target for controlling spinal hyperexcitability in inflammatory pain states.

Topics: Animals; Arthritis; Carrageenan; Cell Separation; Dinoprostone; Disease Models, Animal; Ganglia, Spinal; Kaolin; Knee Joint; Male; Neurons; Pain; Patch-Clamp Techniques; Physical Stimulation; Protein Isoforms; Rats; Rats, Wistar; Receptors, Prostaglandin E; Receptors, Prostaglandin E, EP3 Subtype; Spinal Cord

Opioids are frequently used analgesics, and emesis is a common opioid-induced adverse effect. Methylnaltrexone, a peripheral opioid antagonist, has the potential to block the undesired effects of opioids that are mediated by peripheral receptors while sparing the analgesic effect. We used a rat model of simulated emesis or pica to study if methylnaltrexone decreases morphine induced-kaolin consumption. We observed that after morphine administration, kaolin intake increased significantly compared to intake in the vehicle group, and the increase could be attenuated by ondansetron administration. Methylnaltrexone dose-dependently reduced kaolin ingestion induced by morphine. Morphine and methylnaltrexone did not significantly affect food intake and body weight in the experimental animals. Our data suggest that methylnaltrexone has therapeutic value in treating opioid-induced nausea and vomiting.

Topics: Animals; Antiemetics; Diet; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Therapy, Combination; Injections, Intraperitoneal; Kaolin; Male; Morphine; Naltrexone; Narcotic Antagonists; Ondansetron; Pica; Quaternary Ammonium Compounds; Rats; Rats, Wistar

The latero-capsular division of the central nucleus of the amygdala (CeA) is now defined as the 'nociceptive amygdala' because of its high content of neurons activated exclusively or preferentially by noxious stimuli. Multireceptive (MR) neurons that respond to innocuous and, more strongly, to noxious stimuli become sensitized in arthritis pain. This form of nociceptive plasticity involves presynaptic group I metabotropic glutamate receptors, which increase glutamate release. Here we address the role of N-methyl-D-aspartate (NMDA) and non-NMDA receptors. Extracellular single-unit recordings were made from 25 CeA neurons in anesthetized rats. The neurons' responses to graded brief (15 s) mechanical stimuli, background activity, receptive field size and threshold were measured before and after the induction of kaolin/carrageenan arthritis in one knee and before and during drug applications into the CeA by microdialysis. All neurons examined received excitatory input from the knee(s) and were MR neurons. A selective NMDA receptor antagonist (AP5) inhibited responses to noxious stimuli more potently in the arthritic pain state (n = 6) than under control conditions before arthritis (n = 8) AP5 also inhibited the enhanced background activity and increased responses to normally innocuous stimuli in arthritis, but had no significant effects on these parameters under control conditions. A selective non-NMDA receptor antagonist (NBQX) inhibited background activity and evoked responses under normal control conditions (n = 6) and in arthritis (n = 8) These data suggest that activation of both NMDA and non-NMDA receptors contributes to pain-related sensitization of amygdala neurons.

Topics: 2-Amino-5-phosphonovalerate; Action Potentials; Amygdala; Analysis of Variance; Animals; Arthritis; Disease Models, Animal; Dose-Response Relationship, Drug; Excitatory Amino Acid Antagonists; Kaolin; Male; Neural Inhibition; Neurons; Nociceptors; Pain; Pain Measurement; Physical Stimulation; Quinoxalines; Rats; Rats, Sprague-Dawley; Receptors, AMPA; Receptors, N-Methyl-D-Aspartate

The proper diagnosis of the arrested or the progressive form of hydrocephalus has a critical impact on treatment, but remains difficult. The assessment of early changes in cerebral metabolism might help in the development of adequate non-invasive diagnostic tools. This study examined the alterations in label incorporation in neurotransmitter amino acids and other compounds in kaolin-induced progressive hydrocephalus in rats by means of magnetic resonance spectroscopy (MRS) combined with the administration of [1-13C]glucose and [1,2-13C]acetate. Some 2, 4 and 6 weeks after kaolin injection into the cisterna magna, cerebrum, brainstem and cerebellum were dissected. Interestingly, labelling of most amino acids derived from [1-13C]glucose showed no alterations, whereas labelling from [1,2-13C]acetate was affected. Two weeks after induction of hydrocephalus the taurine concentration was decreased, whereas the concentration of [1,2-13C]lactate was increased in the cerebrum and that of [1,2-13C]GABA in the brainstem. Furthermore, labelling from [1,2-13C]acetate was significantly decreased in [4,5-13C]glutamate, [1,2-13C]glutamate and [1,2-13C]GABA in cerebrum from 4 weeks after hydrocephalus induction. The concentration of N-acetylaspartate, a neuronal marker, was unchanged. However, labelling of the acetyl group from [1-13C]glucose was decreased in cerebellum and brainstem at 6 weeks after the induction of hydrocephalus. As glucose is metabolized predominately by neurones, whereas acetate is exclusively taken up by astrocytes, these results indicate that mostly astrocytic, and only later neuronal, metabolism is disturbed in the kaolin model of hydrocephalus. If verified in patients using in vivo MRS, impaired astrocyte metabolism might serve as an early indication for operative treatment.

Topics: Acetates; Animals; Astrocytes; Biomarkers; Brain Stem; Carbon Isotopes; Disease Models, Animal; Disease Progression; gamma-Aminobutyric Acid; Glucose; Glutamic Acid; Glutamine; Hydrocephalus; Kaolin; Lactic Acid; Magnetic Resonance Spectroscopy; Male; Neurotransmitter Agents; Predictive Value of Tests; Rats; Rats, Sprague-Dawley; Taurine; Telencephalon

To examine the fate of proliferating brain cells in hydrocephalus (Hydro), experimental Hydro was induced in neonatal rats by intracisternal injection of kaolin and, 3 weeks later, the rats were injected with bromodeoxyuridine (BrdU). The BrdU (+) cells were immunohistochemically analyzed by using antibodies against neural (nestin), neuronal (NeuN) and glial (GFAP and MBP) markers in the posterior cerebrum. The percentage of nestin expression for the BrdU (+) cells was 8% in control and increased from 17% in the Hydro to 33% in the Hydro at an earlier stage after the shunt procedure, but was restored to 6% in the Hydro at a later stage after the shunt procedure. The percentages of GFAP expression showed a similar tendency to those of nestin expression. The BrdU (+) cells did not express either NeuN or MBP throughout the experiments.

Topics: Animals; Animals, Newborn; Bromodeoxyuridine; Cerebrum; Disease Models, Animal; Glial Fibrillary Acidic Protein; Hydrocephalus; Immunohistochemistry; Intermediate Filament Proteins; Kaolin; Myelin Basic Protein; Nerve Tissue Proteins; Nestin; Occipital Lobe; Parietal Lobe; Rats; Rats, Wistar

The septohippocampal cholinergic (SHC) system plays an important role in the maintenance of normal memory and learning. However, the fact that memory and learning impairments under hydrocephalic conditions are directly related to the SHC system is less well known. We investigated the relationships between pathological changes in SHC neurons and impairments in memory and learning among hydrocephalic rats.. Rats with kaolin-induced hydrocephalus were prepared with injections of kaolin suspension into the cisterna magna. Learning and memory performance was assessed with the passive avoidance and Morris water maze tests. Ventricular sizes were measured for the lateral and third ventricles. Acetylcholinesterase and choline acetyltransferase immunostaining was performed to investigate degenerative changes in cholinergic neurons in the medial septum and hippocampus.. Hydrocephalic rats demonstrated significant learning and memory impairments in the passive avoidance and Morris water maze tests. Decreased hesitation times in the passive avoidance test and markedly increased acquisition times and decreased retention times in the Morris water maze test indicated learning and memory dysfunction among the hydrocephalic rats. The numbers of cholinergic neurons in the medial septum and hippocampus were decreased in the hydrocephalic rats. The decreases in choline acetyltransferase and acetylcholinesterase immunoreactivity were significantly correlated with enlargement of the ventricles.. Impairment of spatial memory and learning may be attributable to degeneration of SHC neurons. These results suggest that learning and memory impairments in rats with kaolin-induced hydrocephalus are associated with the dysfunction of the SHC system induced by ventricular dilation.

Topics: Animals; Antidiarrheals; Avoidance Learning; Cholinergic Fibers; Disease Models, Animal; Hippocampus; Hydrocephalus; Kaolin; Learning Disabilities; Male; Maze Learning; Memory Disorders; Rats; Rats, Sprague-Dawley; Septum of Brain

Nausea/vomiting are significant side effects associated with the use of chemotherapy in cancer patients. Treatment of nausea/vomiting caused by cisplatin, a potent chemotherapeutic agent and one of the most emetogenic stimuli, requires a combination of different antiemetic drugs. In this study, we investigated the effects of Scutellaria baicalensis, an antioxidant herbal medicine, on cisplatin-induced nausea using a rat model.. Rats react to emetic/nausea-producing stimuli, such as cisplatin, with altered feeding habits, manifested by pica or increased consumption of kaolin (a type of clay). We measured pica in rats to quantify cisplatin-induced nausea, and to evaluate the antinausea effect of pretreatment with S. baicalensis extract (SbE) given intraperitoneally.. Cisplatin at 3 mg/kg induced significant pica accompanied by reduced food intake, suggesting the presence of nausea. Hence, this cisplatin dose was selected for testing the antinausea activity of SbE. Cisplatin-induced pica decreased significantly when animals were pretreated with SbE at doses of 1 mg/kg and 3 mg/kg ( P<0.01). At a higher SbE dose (10 mg/kg), kaolin consumption increased, rather than further decreased, and was significantly different from that in the groups treated with low SbE doses.. SbE pretreatment decreased cisplatin-induced kaolin intake in the rat model of simulated nausea, suggesting that SbE and its active constituent(s) may play a therapeutic role in chemotherapy-induced emesis. Absence of therapeutic effect at the highest tested SbE dose could have been a result of prooxidant activity often associated with excess antioxidant concentration.

Topics: Animals; Antiemetics; Antineoplastic Agents; Cisplatin; Disease Models, Animal; Dose-Response Relationship, Drug; Drugs, Chinese Herbal; Injections, Intraperitoneal; Kaolin; Male; Nausea; Pica; Plant Roots; Rats; Rats, Wistar; Scutellaria baicalensis

Hydrocephalus causes damage to periventricular axons. Tacrolimus, cyclosporine A (CsA) and calpain inhibitors have been shown to protect axons in rat models of acute traumatic brain injury. We hypothesized that these agents would ameliorate the axon damage and behavioral effects in experimental hydrocephalus. Hydrocephalus was induced in 3-week-old rats by injection of kaolin into the cisterna magna. Tests of cognitive and motor function were performed on a weekly basis. In a blinded and randomized manner, tacrolimus (FK506; 3.6 mg/kg body weight) or CsA (10 mg/kg) was administered once daily by subcutaneous injection for 2 weeks, beginning 2 weeks after induction of hydrocephalus. In a separate experiment, calpain inhibitor I (10 mg/kg/day) was administered by continuous subcutaneous infusion. The brains were subjected to histopathological and biochemical analyses after 2 weeks of treatment. There was no statistically significant protection in regard to behavior, brain structure or brain composition in any of the experiments. However, there was biochemical and histological evidence of renal injury following chronic tacrolimus and CsA administration. Calcineurin inhibition does not offer significant protection in this rat model of hydrocephalus.

Topics: Animals; Antidiarrheals; Axons; Calcineurin; Cyclosporine; Disease Models, Animal; Hydrocephalus; Immunosuppressive Agents; Injections, Subcutaneous; Kaolin; Male; Rats; Rats, Sprague-Dawley; Tacrolimus

To study the mechanisms of CSF-outflow in hydrocephalus we used radiological and histological methods to examine pathways of CSF absorption. Two, four and six weeks after occlusion of the cisterna magna by kaolin solution, CSF-dynamics were determined. Direct magnification radiography was used to visualize the outflow of X-ray contrast. Ten rats in each group were sacrificed for histological analysis following ventricular perfusion with marker proteins. ICP was increased to 15 +/- 1 mmHg (mean +/- SD) compared to control animals (7 +/- 2 mmHg) in the four week group. Six weeks following kaolin injection no increase in ICP (6 +/- 1 mmHg) could be demonstrated. Outflow resistance was markedly raised in all animals (1074 +/- 315 mmHg min-1 ml-1) displaying highest values (2160 +/- 960) in the four week group as compared to control animals (504 +/- 71). Cisternography demonstrated blocked cranial absorption and CSF-outflow along lumbosacral nerve roots. Histological examination showed syrinx formation in the cervical and thoracic spinal cord. Marker proteins left the subarachnoid space along thoracic and lumbo-sacral spinal rootlets. The radiological and histological findings and the normalisation of ICP after six weeks at doubled CSF-outflow resistance indicated a recruitment of spinal perineural CSF outflow pathways for the compensation of the disturbed cranial CSF-absorption.

Topics: Animals; Disease Models, Animal; Hydrocephalus; Intracranial Pressure; Kaolin; Radiography; Rats; Spinal Cord

Hydrocephalus is associated with gradual progressive impairment and destruction of cerebral axons and neurons. To provide a comprehensive analysis of gene expression changes in brain due to experimental hydrocephalus we used a DNA microarray screening technique. Hydrocephalus was induced in 3-week-old and 8- to 10-week-old rats by injection of kaolin into cisterna magna. Following induction of hydrocephalus, samples of frontoparietal cerebrum were studied 3 and 36 weeks later in young rats and 1.5 weeks later in adult rats. At the transcriptional level, young rats with subacute hydrocephalus showed overexpression of genes involved in synaptic transmission in parallel to genes associated with protective and compensatory mechanisms. Those with chronic hydrocephalus exhibited some similar changes among synapse-related genes but suppression of other neuronal genes. Expression of myelin-related genes was increased in both groups of rats with early onset hydrocephalus but suppressed in adult rats with acute hydrocephalus. Changes in genes related to extracellular matrix molecules suggest that there might be remodeling in this compartment. Adult rats showed elevated expression of inflammatory genes, likely related to kaolin-induced inflammation, but they failed to show changes in genes involved in compensatory or protective mechanisms. These results indicate that there is an age- and duration-dependent difference in the gene expression profiles of kaolin-induced hydrocephalus and they present avenues for future research.

Topics: Aging; Animals; Chronic Disease; Disease Models, Animal; Gene Expression Profiling; Gene Expression Regulation, Developmental; Hydrocephalus; Kaolin; Magnetic Resonance Imaging; Male; Nerve Tissue Proteins; Oligonucleotide Array Sequence Analysis; Rats; Rats, Sprague-Dawley; RNA, Messenger; Telencephalon

The role of des-Arg9-bradykinin (des-Arg9-BK) and kinin B1 receptor in the plasma extravasation of rat carrageenin-induced pleurisy was investigated employing B1 receptor agonist and antagonists and kininogen-deficient rats. Expression of the B1 receptor mRNA in pleura was induced from 3 to 5 h after the injection of carrageenin into the pleural cavity of Sprague-Dawley rats. Exogenous injection of des-Arg9-BK into the pleural cavity provoked a significant increase in plasma extravasation in 5 h carrageenin-induced pleurisy, but not in 20 min kaolin-induced pleurisy. The level of immunoreactive des-Arg9-BK in the exudate of 5 h carrageenin-induced pleurisy was higher than that of bradykinin (BK). Administration of the B1 receptor antagonists, des-Arg9-[Leu8]-BK or des-Arg9-D-Arg-[Hyp3, Thi5, D-Tic7,Oic8]-BK significantly reduced the exudation rate. However, intrapleural administration of des-Arg9-BK to plasma kininogen-deficient. Brown Norway-Katholiek rats did not result in a further increase in the plasma extravasation. In conclusion, endogenously generated des-Arg9-BK could contribute to the plasma extravasation in carrageenin-induced pleurisy via mediation of the inducible B1 receptor.

Topics: Animals; Antidiarrheals; Bradykinin; Bradykinin Receptor Antagonists; Carrageenan; Cysteine Proteinase Inhibitors; Disease Models, Animal; Enzyme-Linked Immunosorbent Assay; Kaolin; Kininogens; Male; Mice; Plasma; Pleura; Pleurisy; Rats; Rats, Sprague-Dawley; Receptor, Bradykinin B1; Receptors, Bradykinin; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger

Since pain is an important symptom in arthritis, useful behavioral indices for pain in experimental arthritis animal models are important tools for investigative work on arthritis. The purpose of this study was to develop simple and quantifiable behavioral tests, which would represent the level of arthritic pain that develops after induction of inflammation in the knee. Two models of knee joint arthritis were produced: (1) KC model-injection of kaolin and carrageenan into the synovial cavity of the knee, and (2) CFA model-injection of complete Freund's adjuvant into the synovial cavity of the knee. The following three variables were measured before and at various times after the induction of arthritis. As an estimate of the degree of edema, the circumference of the knee was measured. As pain indices, (1) the vocalization threshold of compression force applied to the knee joint was measured to represent tenderness of the joint, and (2) the struggle threshold of the knee extension angle was measured to represent a reduction in range of motion in the arthritic joint. A time course study showed that behavioral changes last for at least 1 week for the KC model and at least 2 weeks for the CFA model. Correlation studies showed that all three variables significantly correlated with each other in both the KC and CFA arthritic models. Systemically injected morphine produced a partial reversal of these indices with the expected time course and dose response of a morphine-induced analgesic. It is concluded that two variables, the struggle threshold for knee extension and the vocalization threshold for knee compression, could be used as simple and useful pain indices in experimental models of arthritis.

Topics: Analgesics, Opioid; Animals; Arthritis; Biomechanical Phenomena; Carrageenan; Disease Models, Animal; Edema; Freund's Adjuvant; Kaolin; Knee Joint; Male; Morphine; Motor Activity; Pain; Pain Measurement; Pain Threshold; Range of Motion, Articular; Rats; Rats, Sprague-Dawley; Stress, Psychological; Vocalization, Animal

In general, rats and mice have not been used in research on emesis because they do not vomit. However, emetogenic stimuli such as anticancer drugs, apomorphine, copper sulfate and rotation induced pica, a behavior characterized by eating nonfood substances such as kaolin, in rats. We also found that cisplatin induced pica in mice, but it was rather difficult to determine the exact kaolin consumption in this species. In this study, we prepared kaolin pellets mixed with carmine, a dye not absorbed in the gastrointestinal tract, and estimated kaolin consumption by determination of carmine excreted in feces. Cisplatin (5 mg/kg) caused a significant increase in kaolin consumption (saline: 0.15 +/- 0.08 g vs. cisplatin: 0.45 +/- 0.16 g) and pretreatment with the 5-HT3 receptor antagonist, ondansetron (2 mg/kg), suppressed the increased consumption (vehicle: 0.33 +/- 0.05 g vs. ondansetron: 0.13 +/- 0.04 g). These findings suggested that the exact kaolin consumption could be quantified by the determination of carmine in feces and that mice could be useful for studying emesis.

Topics: Animals; Antiemetics; Antineoplastic Agents; Carmine; Cisplatin; Disease Models, Animal; Eating; Feces; Kaolin; Male; Mice; Mice, Inbred ICR; Ondansetron; Pica; Vomiting

Effects of the angiotensin-converting enzyme (ACE) inhibitors, imidapril and enalapril, on kaolin-induced writhing reaction, which is believed to be caused by bradykinin (BK), were examined in mice. The number of writhes was increased significantly by 200 microg/kg of imidapril and by 100 and 200 microg/kg of enalapril. The intensity of writhing reaction was significantly suppressed by 1,000 nmol/kg of icatibant, a selective bradykinin B2 receptor antagonist, in the imidapril-, but not in the enalapril-treated groups. These results suggest that the potentiating effect of enalapril on kaolin-induced writhing reaction is greater than that of imidapril. This might depend on the difference of their inhibitory effects on BK degradation.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Bradykinin; Bradykinin Receptor Antagonists; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Synergism; Enalapril; Imidazoles; Imidazolidines; Kaolin; Male; Mice; Mice, Inbred ICR; Pain

A rat model was developed to elucidate the role of excitatory amino acids and spinal subarachnoid block in the genesis of post-traumatic syringomyelia. This excitotoxic model produces intramedullary cavities rather than the dilation of the central canal (canalicular syringomyelia) created by previous animal models.. To produce extracanalicular cysts in the rat spinal cord with quisqualic acid, a potent agonist of multiple excitatory amino acid receptors, and to compare the effects of excitotoxic injury only with that of excitotoxic injury and subarachnoid block with kaolin.. In post-traumatic syringomyelia, primary injury and excitotoxic cell death secondary to elevated levels of excitatory amino acids may initiate a pathologic process leading to the formation of spinal cavities. Subarachnoid block by arachnoiditis may promote enlargement of the cavities.. Three control rats received a unilateral injection of normal saline into the spinal cord, and another five rats received an injection of kaolin into the spinal subarachnoid space. Quisqualic acid was injected unilaterally into the spinal cord of 20 rats, and 13 additional rats received a unilateral injection of quisqualic acid into the spinal cord after injection of kaolin into the subarachnoid space. Histologic and immunocytochemical assessments were undertaken.. In the control groups, no parenchymal cyst developed in any of the animals. Spinal cord cyst formation was observed in 16 of 19 animals in the quisqualic acid groups, but no cysts exceeding two segments in the length of the spinal cord developed in any of the rats. Much larger cavities were seen in 9 of 11 animals in the group with quisqualic acid and kaolin, and cysts exceeding two segments developed in all 9 of these (9/11; 82%).. In post-traumatic syringomyelia, excitotoxic cell death occurring secondarily to elevated levels of excitatory amino acids may contribute to the pathologic process leading to the formation of spinal cord cysts. Subarachnoid block by arachnoiditis is likely to cause enlargement of the cavity.

Topics: Animals; Arachnoiditis; Astrocytes; Cysts; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Interactions; Excitatory Amino Acid Agonists; Excitatory Amino Acids; Fluorescent Antibody Technique, Indirect; Glial Fibrillary Acidic Protein; Immunohistochemistry; Kaolin; Longevity; Male; Microinjections; Quisqualic Acid; Rats; Rats, Sprague-Dawley; Spinal Cord; Spinal Cord Injuries; Subarachnoid Space; Syringomyelia

Topics: Animals; Antidiarrheals; Cerebral Ventricles; Diffusion; Disease Models, Animal; Extracellular Space; Ganglionic Stimulants; Hydrocephalus; Kaolin; Quaternary Ammonium Compounds; Rats

Topics: Animals; Cisterna Magna; Disease Models, Animal; Evoked Potentials, Auditory; Evoked Potentials, Visual; Hydrocephalus; Kaolin; Male; Rats; Rats, Wistar

Objective. To test the validity of an animal model in selecting anti-motion sickness drugs, and compare the effects of two drugs. Method. Anti-motion sickness effects of two drugs (Cyclizine and Scopolamin-d-amphetamin compound) were observed in rats with motion sickness (MS) induced by rotatory stimulation and the amount of Kaolin ate by rats was taken as an evaluation criterion. Result. The consumption of Kaolin by the rats decreased significantly after administration of both drugs, and the effect of Scopolamin-d-amphetamin compound was better than those of Cyclizine under the same condition. Conclusion. It suggests that the rat model of motion sickness is practical and useful in studying anti-motion sickness drugs.

Topics: Animals; Antiemetics; Central Nervous System Stimulants; Cyclizine; Dextroamphetamine; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Combinations; Kaolin; Motion Sickness; Pica; Rats; Scopolamine

The source of fluid and the mechanism of cyst enlargement in syringomyelia are unknown. It has been demonstrated that cerebrospinal fluid (CSF) normally flows from the subarachnoid space through perivascular spaces and into the spinal cord central canal. The aim of this study was to investigate whether this flow continues during cyst formation in an animal model of syringomyelia and to determine the role of subarachnoid CSF flow in this model.. The intraparenchymal kaolin model of noncommunicating syringomyelia was established in 78 Sprague-Dawley rats. Horseradish peroxidase was used as a tracer to study CSF flow at 1 day, 3 days, 1 week, and 6 weeks after kaolin injection. CSF flow was studied at 0, 10, and 30 minutes after horseradish peroxidase injection into the cisterna magna or thoracic subarachnoid space.. The central canal became occluded at the level of the kaolin injection and at one or more rostral levels. Segments of the central canal isolated between occlusions gradually dilated, and axonal retraction balls were detected in the surrounding white matter. There was a partial blockage of subarachnoid CSF flow at the site of the kaolin injection, both in a rostral-caudal direction and in a caudal-rostral direction. Horseradish peroxidase was detected at all time points, in a distinctive pattern, in perivascular spaces and the central canal. This pattern was seen even where segments of the central canal were isolated and dilated.. In this animal model, noncommunicating syringes continue to enlarge even when there is evidence that they are under high pressure. There may be an increase in pulse pressure rostral to the block of subarachnoid CSF flow, causing an increase in perivascular flow and contributing to syrinx formation. The source of fluid in noncommunicating syringomyelia may be arterial pulsation-dependent CSF flow from perivascular spaces into the central canal.

Topics: Animals; Cerebrospinal Fluid; Disease Models, Animal; Horseradish Peroxidase; Injections, Intraventricular; Injections, Spinal; Kaolin; Male; Rats; Rats, Sprague-Dawley; Spinal Cord; Subarachnoid Space; Syringomyelia

We examined with electrophysiological techniques the effects of experimentally induced inflammation on the mechanosensitive afferent units in the rotator cuff of the shoulder joint of 21 rabbits. We identified 21 mechanosensitive units belonging to group III. 12 units had mechanical thresholds of > 7.0 g and 9 units had thresholds of < 7.0 g. After injection of inflammatory agents, kaolin and carrageenan, into the joint space, ongoing afferent discharge rates increased in all units. The average discharge rate increased significantly from 7 imp/s to 15 imp/s after injection. 5 units had a decreased mechanical threshold after the injection. Acute inflammation seems to have an excitatory and sensitizing effect on the high- and low-threshold units in the rotator cuff.

Topics: Acute Disease; Afferent Pathways; Animals; Carrageenan; Disease Models, Animal; Electrophysiology; Humans; Inflammation; Kaolin; Male; Mechanoreceptors; Rabbits; Rotator Cuff; Sensory Thresholds; Shoulder Joint; Tendinopathy

We used three types of specialized micro-balloons 0.7-1.35 mm in outer diameter instead of kaolin to develop a reproducible rat model of hydrocephalus with a low experimental mortality. The micro-balloon was inserted 6 mm deep into the cisterna magna via a burr hole immediately behind the lambda. The angle of introduction was 50 degrees. We also set up kaolin-induced hydrocephalic models in 25 rats as controls. The kaolin model revealed 52% mortality with an 80% induction rate of hydrocephalus, while the balloon model showed 9% mortality with a 60% induction rate. Balloon-induced hydrocephalus was maximal at 1 week and tended to decrease after 2-3 weeks. The pathological findings were not different between the two models. We concluded that the micro-balloon model for hydrocephalus is an easily reproducible model with low experimental mortality.

Topics: Animals; Catheterization; Disease Models, Animal; Female; Hydrocephalus; Implants, Experimental; Kaolin; Male; Rats; Rats, Sprague-Dawley

The development of kaolin-induced hydrocephalus in adult hamsters was monitored by measuring changes in intracranial pressure (ICP), ventriculomegaly (VG) and whole-brain specific gravity (SG). Controls were intact or sham operated animals. Relative to controls, ICP of experimental animals increased at 24 h post intracisternal kaolin injection (by approximately 7-fold), reached a maximum on day 6 (by approximately 12-fold) and remained markedly elevated through day 15 (by approximately 5-fold). Ventricles differed in time of onset of distension (third: day 1, lateral: day 2, fourth: day 4) and in time of maximum ventriculomegaly (fourth: day 6; third: day 7; and lateral: day 9). Ventricular distension resulted in alterations in the ependyma; cilia were lost and apical cell surfaces were distorted. The ependyma was ruptured and the subjacent neuropil was exposed to the cerebrospinal fluid in some regions. Whole-brain SG remained constant in controls but declined in hydrocephalic hamsters after day 3 post-kaolin injection and reached its nadir on day 9 when whole-brain water content was 18% greater than in controls. Consistent with the fact that causal relationships exist between increased ICP, ventricular distension and brain edema, the alterations in each parameter occurred sequentially rather than simultaneously, and the time-course of each manifestation of hydrocephalus differed. The data suggest that the pathophysiology of kaolin-induced hydrocephalus in the hamster is tri-phasic: an initial period of rapid change, a brief interval of maximum alteration, and a subsequent period of compensation.

Topics: Age Factors; Animals; Cilia; Cricetinae; Disease Models, Animal; Ependyma; Female; Hydrocephalus; Intracranial Pressure; Kaolin; Mesocricetus; Microscopy, Electron, Scanning; Pharmaceutic Aids; Specific Gravity; Subarachnoid Space

The histological changes associated with syringomyelia after reduction of the syrinx size were investigated after cerebrospinal fluid shunting in experimental syringomyelia in the rabbit. Five weeks after syringomyelia was induced by the injection of kaolin into the cisterna magna in Japanese white rabbits, ventriculosubgaleal shunting or syringoepidural shunting were performed. After 1 week magnetic resonance (MR) imaging and histological examination were then carried out. Five of 11 shunted animals showed postoperative reduction of syrinx size on MR imaging. Grossly, some specimens showed cavity collapse and parenchymal healing, and others showed a small residual syrinx in the dorsal horn. The most dramatic histological changes occurred in the gray matter. Specimens with syrinx collapse showed rarefaction and tearing of the gray matter, with mild glial reaction. The edematous gray matter showed both degeneration and regeneration, with neuronal processes surrounded by edema fluid. Reactive astrocytes were observed mainly at the margin of the residual syrinx. Some astrocytic processes invested the extraaxonal space and gray matter lacked supportive tissue. Greater reduction of the syrinx after shunting operation was correlated with more regeneration and less degeneration, and the white matter was edematous and histological changes were milder. Syrinx shrinkage occurred after shunting in this experimental model of syringomyelia. The selective vulnerability of gray matter even after shunting may explain discrepancies between imaging findings and clinical features in this disease. The study supports the potential benefit from early treatment, considering the associated morphological findings of regeneration.

Topics: Animals; Cerebrospinal Fluid Shunts; Disease Models, Animal; Kaolin; Magnetic Resonance Imaging; Nerve Regeneration; Photomicrography; Rabbits; Spinal Cord; Syringomyelia

The severity and progression of ventricular enlargement, the occurrence of cerebral edema, and the localization of ischemic metabolic changes were investigated in a rat model of hydrocephalus, using in vivo 1H MR spectroscopic imaging (SI) and diffusion weighted MRI (DW MRI). Hydrocephalic rats were studied 1, 2, 4, and 8 weeks after injection of kaolin into the cisterna magna. Parametric images of the apparent diffusion coefficient (ADC) revealed a varying degree of ventriculomegaly in all rats, with different time courses of ventricular expansion. Extracellular white matter edema was observed during the early stages of hydrocephalus, most extensively in cases of progressive ventriculomegaly. In gray matter regions, ADC values were not changed, compared with controls. In case of fatal hydrocephalus, high lactate levels were observed throughout the whole brain. In all other rats, at all time points after kaolin injection, lactate was detected only in voxels containing cerebrospinal fluid. This suggests accumulation of lactate in the ventricles, and/or an ongoing periventricular production of lactate as a consequence of cerebral ischemia in experimental hydrocephalus.

Topics: Acute Disease; Analysis of Variance; Animals; Brain; Brain Edema; Brain Ischemia; Chronic Disease; Diagnosis, Differential; Disease Models, Animal; Hydrocephalus; Kaolin; Lactic Acid; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Male; Rats; Rats, Wistar; Time Factors

Animal scoliosis model associated with syringomyelia.. To investigate the pathogenesis of scoliosis produced in dogs with kaolin-induced syringomyelia.. Kaolin injected into the cisterna magna produces basilar arachnoiditis, leading to hydrocephalus and syringomyelia. There have been no reports on scoliosis associated with kaolin-induced syringomyelia.. Kaolin was injected percutaneously into the cisterna magna of 11 beagles 6-8 weeks after birth. Roentgenograms, computed tomography, and magnetic resonance imaging were obtained. The spinal cord and the paraspinal muscles were examined histologically. Structural changes of the vertebral column were analyzed with calcein and tetracycline labeling.. Hydrocephalus occurred in nine dogs. A communicating syringomyelia appeared in five dogs. Mild scoliosis developed in two dogs, and severe cervical scoliosis in one dog. In the syringomyelia cases, acute or subacute inflammatory changes were found in the spinal cord. Damage of the anterior and posterior horn cells was more marked in the scoliotic animals than in the nonscoliotic animals. In three of the syringomyelia cases, including two scoliosis cases, the paraspinal muscles revealed neurogenic changes. The deformed vertebrae appeared to diminish rather than to increase the deformity in severe scoliosis.. The exact mechanism of the development of scoliosis could not be identified, although an etiologic relation with malfunction of the central nervous system was noted. This model may be useful to study scoliosis experimentally.

Topics: Animals; Cisterna Magna; Disease Models, Animal; Dogs; Injections; Kaolin; Magnetic Resonance Imaging; Muscle, Skeletal; Radiography; Scoliosis; Spinal Cord; Spine; Syringomyelia

In human hydrosyringomyelia and in the late stage of experimental syringomyelia, the spinal cord tissue adjacent to the syrinx is exposed to a similar pathophysiologic condition. We investigated the ultrastructural changes in the late stages of kaolin-induced syringomyelia, and in addition, we presented magnetic resonance imaging (MRI) findings of the cervicomedullary junction and syrinx, and the nature of edema in the spinal cord of this experimental model.. Syringomyelia was induced in rabbits by intracisternal injection of kaolin. MRI was performed at 6 weeks, and 6 and 12 months following injection, and the animals were killed by transcardial perfusion of formaldehyde solution and examined by transmission electron microscopy. Evans blue was injected intravenously in six rabbits, 6 weeks and 12 months following kaolin injection and was examined by confocal laser scanning microscopy.. MRI showed that the syrinx communicated with the fourth ventricle in most animals. Demyelination of varying degrees and slight edematous change were seen in the perisyrinx white matter. No extravasation of Evans blue was seen by confocal microscopy. Abundant astrocytic proliferation with a large number of glial filaments was seen at the margin of the syrinx and between the axons in the perisyringeal region. The perivascular space enlargement occurred in both the gray and white matter. The endothelial junctions appeared intact. Regenerating axons and remyelination by oligodendrocytes were seen occasionally.. The MRI confirmed the communication between the fourth ventricle and the syrinx. The ultrastructural changes were almost identical to those of the early stage syrinx, but the astrocytic proliferation was more severe, and the edema was less in the late stage. The perisyrinx edema appeared to be of the interstitial type, as in hydrocephalus. Axonal degeneration and demyelination continued with abortive attempt at regeneration and remyelination in the less edematous late stage, which might be the cellular basis for the persistence or worsening of clinical symptoms and signs in the chronic stage of syringomyelia even after surgical treatment.

Topics: Animals; Chronic Disease; Disease Models, Animal; Kaolin; Magnetic Resonance Imaging; Microscopy; Nerve Regeneration; Rabbits; Spinal Cord; Structure-Activity Relationship; Syringomyelia; Time Factors

1. The effects of a novel, potent and orally active nonpeptide bradykinin B2 receptor antagonist, FR167344 (N-[N-[3-[(3-bromo-2-methylimidazo[1,2-a]pyridin-8-yl)oxymethyl]-2 ,4-dichlorophenyl]-N-methylaminocarbonylmethyl]-4-(dimethylamin ocarbonyl) cinnamylamide hydrochloride) were tested in three different in vivo models of inflammation. 2. Oral administration of FR167344 inhibited carrageenin-induced paw oedema in rats (carrageenin: 1%, 0.1 ml per animal, intraplantar), with an ID50 of 2.7 mg kg(-1) at 2 h after carrageenin injection (n=10 or 11). 3. Oral administration of the compound also inhibited kaolin-induced writhing (kaolin: 250 mg kg(-1), i.p.) in mice, with ID50 of 2.8 mg kg(-1) in 10 min writhing and 4.2 mg kg(-1) in 15 min writhing (n=19 or 20). 4. Additionally, oral administration of FR167344 inhibited caerulein-induced pancreatic oedema with an ID50 of 13.8 mg kg(-1) as well as increases in amylase and lipase of blood samples with ID50 of 10.3 and 7.4 mg kg(-1), respectively, in rats (n=10). 5. These results show that FR167344 is an orally active, anti-inflammatory and anti-nociceptive agent in carrageenin-induced paw oedema, kaolin-induced writhing and caerulein-induced pancreatitis. FR167344 may have therapeutic potential against inflammatory diseases by oral administration and it may be a useful tool for studying the involvement of B2 receptors in various in vivo models of inflammation.

Topics: Administration, Oral; Animals; Antidiarrheals; Bradykinin Receptor Antagonists; Carrageenan; Ceruletide; Disease Models, Animal; Excipients; Gastrointestinal Agents; Inflammation; Kaolin; Male; Mice; Mice, Inbred ICR; Pain; Pancreatitis; Pyridines; Rats; Rats, Sprague-Dawley; Receptor, Bradykinin B2; Receptors, Bradykinin

In this morphological study the authors investigated whether spinal cord cavitation, produced in young mongrel dogs that had been rendered hydrocephalic by cisternal injection of kaolin, consists of a dilated central canal or intramedullary cavities. Hydrocephalus was noted in 50 of 56 dogs treated with kaolin. Of the 50 hydrocephalic young dogs, 29 were shown to have central canal dilation that was prominent at the thoracic level and 21 to have cervical intramedullary cavities in the posterior column and/or the posterior horn. In 11 dogs from the latter group these cavities were demonstrated to have no communication with the central canal. This finding could not be explained by the hydrodynamic theory. On histopathological examination, myelomalacia and hemorrhagic infarction following ventricular shunting were noted adjacent to the cervical cavities, which suggested vascular impairment. A perfusion study revealed insufficient blood flow within the cervical cord at the level of the intramedullary cavities. A close correlation between the vascular insufficiency of the cervical cord and the pressure cone resulting from significant hydrocephalus was observed. The latter may cause cervicomedullary compression at the foramen magnum, affecting the venous drainage of the cervical cord below that level, resulting in intramedullary cavitation. Accordingly, vascular impairment was thought to play a significant role in the development of cervical syrinx formation in our kaolin model. The current results may provide a reasonable explanation for the formation of noncommunicating cervical syringomyelia in Chiari I malformation.

Topics: Animals; Disease Models, Animal; Dogs; Histocytochemistry; Hydrocephalus; Kaolin; Spinal Cord; Syringomyelia

1. Injection of kaolin and carrageenan into the knee joint of cats or monkeys resulted in an acute inflammation. Four hours after injection of the knee joint, efferent activity could be evoked in articular afferent fibers and in dorsal root filaments. We interpret this efferent activity to be dorsal root reflexes (DRRs). Under our experimental conditions, the DRRs were generally synchronized compound action potentials, although in some cases single-unit activity was also observed. 2. DRRs were not produced in animals with uninflamed knee joints and normal body temperatures. 3. Recordings from two different sites on cut dorsal root filaments ipsilateral to the inflamed knee joint allowed the determination of the conduction velocities of groups of afferent fibers carrying DRRs. The DRRs occurred in A beta-, A delta-, and C fibers. However, in these experiments the peripheral destination of the afferent fibers was unknown. 4. To prove that DRRs occurred in joint afferents, recordings were made from two different sites on the proximal stump of the medial articular nerve that innervated the inflamed knee. The DRRs were again found in all fiber types, i.e., group II, III, and IV (A beta, A delta, and C) articular afferent fibers. 5. Compound DRRs were recorded from the central end of a cut dorsal root filament after electrical stimulation at C fiber intensity of a dorsal root adjacent to the filament. This DRR activity was eliminated by extensive dorsal rhizotomies of the L2-S1 roots.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Action Potentials; Afferent Pathways; Animals; Arthritis; Cats; Disease Models, Animal; Efferent Pathways; Ganglia, Spinal; Inflammation; Joints; Kaolin; Macaca mulatta; Nerve Fibers; Reflex

Much has been written about the relationship between the pulse pressure (PP) of the intracranial pressure pulse wave (ICPPW) and ventricle dilatation. Some data suggest that high PP is the cause of ventricle dilatation, and other authors have reported that high PP results from decreased intracranial compliance. In order to clarify these points, the amplitude of PP and pressure-volume response (PVR: an indicator of intracranial compliance) were measured in bilateral ventricles using Hochwald's hydrocephalic model (right-left difference in ventricle size is clear due to hemicraniectomy). Hydrocephalus was induced by means of intracisternal injection of a kaolin powder solution to dogs. The mean ICP, amplitude of the PP, PVR and ventricle size (estimated by MR imaging) were evaluated in pathologic conditions induced by the following procedures. Group A, control: kaolin-induced hydrocephalus without craniectomy; group B: kaolin-induced hydrocephalus with right-sided craniectomy; group C: kaolin-induced hydrocephalus with right-sided craniectomy and dural resection; group D: kaolin-induced hydrocephalus with right-sided craniectomy, dura resection and temporal muscle resection. Using MR imaging, the same degree of symmetrical ventricle dilatation was identified in all groups except group D. Group D alone demonstrated a difference in ventricular size (craniectomy side > non-craniectomy side). There was no appreciable difference in mean ICP between any two groups. However, the amplitude of PP and the PVR decreased stepwise from group A to group D. The difference in the amplitude of the PP and PVR between the right and left ventricles was not significant in any group.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Cerebral Ventricles; Craniotomy; Dilatation, Pathologic; Disease Models, Animal; Dogs; Hydrocephalus; Intracranial Pressure; Kaolin; Magnetic Resonance Imaging

Mitchell et al. (1976, 1977) suggested that pica, eating of nonnutritive substances such as kaolin, is an illness-response behavior in rats. In the present study, we first confirmed their suggestion and then examined the effects of antiemetics on emetic-induced pica in rats. Intraperitoneal injection of apomorphine induced dose-dependent kaolin consumption. Pretreatment with domperidone inhibited apomorphine-induced kaolin intake. Oral administration of copper sulfate and intraperitoneal injection of cisplatin also induced dose-dependent kaolin consumption. Pretreatment with ondansetron inhibited cisplatin-induced kaolin intake. These findings suggest that pica in rats was induced through 1) dopamine D2 receptors in the chemoreceptor trigger zone, and 2) the stomach, partly via 5-HT3 receptors in the visceral afferents in the stomach wall. The present findings support the conclusion that pica in rats is analogous to vomiting in other species and suggest that pica in rats is mediated by the same mechanisms as vomiting in humans. Accordingly, we extended the utility of the animal model to pharmacological research of emesis with pica as an analogue to emesis.

Topics: Animals; Antiemetics; Apomorphine; Cisplatin; Copper; Copper Sulfate; Disease Models, Animal; Domperidone; Dose-Response Relationship, Drug; Food; Kaolin; Male; Ondansetron; Pica; Rats; Rats, Wistar; Vomiting

This report describes a new and reliable technique for producing experimental noncommunicating syringomyelia. In 30 rats, 1.2 to 1.6 microliters of kaolin was microinjected into the dorsal columns and central gray matter of the spinal cord at C-6. The inoculations caused transient neurological deficits in four animals and no deficits in 26 animals. Within 24 hours, kaolin and polymorphonuclear leukocytes entered the central canal and drained rostrally. The clearance of inflammatory products induced a proliferation of ependymal cells and periependymal fibrous astrocytes, which formed synechiae and obstructed the canal at the level of injection and at one or more levels up to C-1. In 22 animals followed for 48 hours or longer, the upper end of the central canal became acutely dilated and formed an ependyma-lined syrinx that enlarged to massive dimensions within 6 weeks. The rostral syrinxes did not communicate with the fourth ventricle and were not associated with hydrocephalus. The histological findings in acute noncommunicating syringomyelia were characterized by progressive stretching and thinning of the ependyma, elongation of intracanalicular septae, and the formation of periependymal edema. After 3 weeks, there was progressive compression of the periependymal tissues associated with stretching of axons, fragmentation of myelin sheaths, and the formation of myelin droplets. These findings and the sequence in which they evolved were identical in most respects to those occurring in acute and subacute noncommunicating hydrocephalus.

Topics: Animals; Astrocytes; Disease Models, Animal; Ependyma; Epithelium; Injections, Spinal; Kaolin; Male; Myelin Sheath; Rats; Rats, Sprague-Dawley; Spinal Cord; Syringomyelia

In order to produce syringomyelia, localized arachnoiditis was created in adult New Zealand albino rabbits and Wistar rats by the injection of kaolin into the thoracic spinal subarachnoid space and incision of the dura mater of the thoracic spinal cord. The rabbits and rats were divided into 3 groups; the control group, dural incision group (DG) and kaolin injection group (KG). Each rabbit was sacrificed at 4, 8, 12 and 16 weeks after the operation. Each rat was sacrificed at 8 and 16 weeks after the operation. Cavity formation in the cord of all rabbits was examined by ultrasound. All animals were perfused with 10% neutral beffered formalin at 150 cm H2O pressure, and histological examination was performed with Luxol fast blue (LFB) and hematoxylin and eosin (H&E) stains. Results obtained: (1) Cavity formation was noted in 6 of 16 DG of rabbit (37.5%), 5 of 16 KG of rabbit (31.2%) and 2 of 9 KG of rat (22.2%) with histological verification. With use of ultrasound, cavity was noted in 3 of 16 DG rabbits (12.5%) and 2 of 16 KG rabbits (18.8%). (2) Cavity formation was present in the cord adjacent to the marked adhesive arachnoiditis both in rabbits and in rats. (3) Cavity was noted in the ischemic area. (4) In 2 rabbits in which kaolin encircled whole surface of the spinal cord, hydromyelia was formed communicating with enlarged central canal caudad from the kaolin subarachnoid block. (5) Histological examination showed obliteration or narrowing of lumen of the small pial vessels involved in the adhesive arachnoiditis. In the cord parenchyma adjacent to the arachnoiditis, multiple spots of demyelination due secondary to ischemia demonstrated by LFB stain were noted. On the other hand, in the cord with the pia-arachnoid remained uninvolved, no demyelination was observed. (6) Localized adhesive arachnoiditis consisted of proliferation of fibrous tissue, lymphocytic infiltration and obliterating processes of small pial vessels involved in it. These data suggest that the cavitation within the cord would be induced by the ischemia, and hydromyelia would be produced by the pressure dissociation between the spinal subarachnoid space and the central canal.

Topics: Animals; Arachnoiditis; Disease Models, Animal; Dura Mater; Kaolin; Rabbits; Rats; Rats, Wistar; Syringomyelia

Hydrocephalus was induced in adult greyhounds by intracisternal kaolin. Intraventricular pressure (IVP) was monitored in the conscious animal for 2 weeks using a small implantable sensor, and the time-course of IVP change was characterized. Intraventricular pressure increased significantly within 36 h of kaolin infusion and gradually subsided to normal values within 1 week. Enlargement of the lateral ventricles was not observed during the early phase of intracranial hypertension (less than 2 days). Evolving hydrocephalus and intracranial hypertension increased the elasticity (dP/dV) of the sagittal sinus. This effect was statistically significant (p < 0.05) and is possibly reversible in the acute stage. Normotensive hydrocephalus (1 and 2 weeks after kaolin) was associated with an irreversible increase in resistance to outflow (i.e., increased sagittal sinus elasticity). Sagittal sinus venography of animals with obvious ventricular enlargement (at least 1 week after kaolin) showed development of venous collaterals and atypical outflow pathways.

Topics: Animals; Cerebral Ventricles; Cerebrospinal Fluid Pressure; Chronic Disease; Cranial Sinuses; Disease Models, Animal; Dogs; Elasticity; Hydrocephalus; Intracranial Pressure; Kaolin; Venous Pressure

We found a novel and highly selective synthetic inhibitor of plasma kallikrein (PK), called PKSI-527; the Ki value was 0.81 microM. PKSI-527 inhibited the bradykinin (BK) generation induced by kaolin and prolonged partial thromboplastin time (PTT). PKSI-527 prevented the decrease of fibrinogen (Fg) levels due to i.v. injection of ellagic acid in mice and ameliorated the endotoxin (ET)-induced DIC in rats.

Topics: Animals; Blood Coagulation; Bradykinin; Disease Models, Animal; Disseminated Intravascular Coagulation; Endotoxins; Fibrinogen; Humans; In Vitro Techniques; Kallikreins; Kaolin; Kinetics; Mice; Partial Thromboplastin Time; Phenylalanine; Rats; Tranexamic Acid

Although previous ultrasonographic studies did monitor ventricular enlargement successfully in experimentally-induced models of feline hydrocephalus, the resolution of neuroanatomic detail was relatively poor after placement of a ventriculoperitoneal (VP) shunt because the skull had ossified over the coronal sutures. Therefore, the present study employed magnetic resonance imaging to follow the progression of ventriculomegaly more accurately, as well as to evaluate the compensatory effects of VP shunting. Hydrocephalus was induced in kittens between 7 and 10 days old by injection of kaolin into the cisterna magna. Age-matched controls received similar injections of saline. At 9 to 14 days after the kaolin injection, the hydrocephalic animals received VP shunts. Anesthetized kittens were scanned at various intervals before and after shunt placement and were killed for morphological correlation. The features observed on the magnetic resonance imaging scans were consistent with the gross morphological changes that accompanied ventricular enlargement. The lateral ventricle began to enlarge as early as 1 day after the kaolin injection, and within 3 days, both the occipital and temporal horns, along with the 4th ventricle, showed signs of moderate dilatation. By 5 days, a bilateral communication had been established through the septum pellucidum. Continued expansion of the ventricular system occurred from 6 to 20 days after injection, to the point where the cerebral cortex was reduced to less than 25% of its original thickness. The internal capsule was stretched and edematous, the caudate nucleus was compressed ventrolaterally, and the cerebellar hemispheres were eroded and/or compressed. Animals in which shunts were successfully placed demonstrated a dramatic improvement in behavior, and a reduction of about 50% in the size of the lateral ventricles within 2 days. In some cases, the lateral ventricles became slit-like within 1 week. When they were killed, about half of the animals that received shunts exhibited mild to moderate ventriculomegaly. These results indicate that magnetic resonance imaging is an excellent method for visualizing the morphological changes associated with this animal model, that these alterations occur soon after the onset of hydrocephalus, and that VP shunting can successfully reduce ventriculomegaly.

Topics: Animals; Brain; Cats; Cerebrospinal Fluid Shunts; Disease Models, Animal; Hydrocephalus; Kaolin; Magnetic Resonance Imaging; Time Factors

Antibody microprobes were used to study the release of immunoreactive neurokinin A into the spinal cord of anaesthetised cats during and following injection of a knee joint with kaolin and carrageenan. A basal level of immunoreactive neurokinin A was detected prior to any noxious stimuli. Innocuous mechanical joint stimuli (flexion or pressure) did not alter this basal level of release. However, on injection of kaolin and carrageenan into a knee joint, evidence of release into the ipsilateral spinal cord was immediately observed. Initially, immunoreactive neurokinin A was detected in 2 regions: one at the dorsal surface of the spinal cord and the other centred on the superficial dorsal horn. Within 1 h of joint injection, however, immunoreactive neurokinin A was detected throughout the dorsal horn and the adjacent white matter. The extensive spread and persistence of immunoreactive neurokinin A in the spinal cord may underlie some of the prolonged excitability changes evoked by brief noxious stimuli and peripheral inflammation reported by other laboratories.

Topics: Acute Disease; Animals; Arthritis; Autoradiography; Carrageenan; Cats; Disease Models, Animal; Kaolin; Molecular Probes; Neurokinin A; Spinal Cord; Stress, Mechanical

This study was done with the aid of experimental models of inflammation provoked in air pouch, which was made subcutaneously on the back of rats, by applying a carrageenin solution or a suspension of kaolin in a carboxymethylcellulose solution as an irritant. Bradykinin in the inflammatory sites, determined by an enzyme immunoassay method, were comparatively high in the earliest stage of inflammation in both the models and responsible for the exudative reactions. With the passage of time, i.e. within 20 min in the case of kaolin and 120 min in carrageenin, tissue kininase entered the inflammatory site and reduced bradykinin to a very low level, though bradykinin was still being generated very actively. In this later stage, bradykinin collaborates with prostaglandin to bring about a significant increase in the vascular permeability.

Topics: Animals; Bradykinin; Capillary Permeability; Carrageenan; Disease Models, Animal; Immunoenzyme Techniques; Inflammation; Kaolin; Male; Peptidyl-Dipeptidase A; Rats; Rats, Inbred Strains; Time Factors

Norepinephrine (NE) changes during hydrocephalus, and the effects of surgical decompression on these changes, were studied using a new model of neonatal hydrocephalus. Kittens 4 to 10 days old received intracisternal injections of a sterile solution of 25% kaolin. Control kittens were injected similarly with sterile injectable saline. Ultrasonography was used to follow the progression of ventriculomegaly and the initial effects of the shunts. A subgroup of hydrocephalic animals was shunted using a cerebrospinal fluid lumbar-peritoneal catheter. Hydrocephalic animals were killed at approximately 25 days of age (16-21 days after kaolin injection). Surgical decompression was performed at 12, 16, and 17 days after kaolin injection; these animals were killed 30 days after the shunts were inserted. Control animals were killed at 29 and 53 days of age, to correlate with the ages of the hydrocephalic and shunted animals, respectively. Cortical samples equivalent to Brodmann's areas 4, 22, and 17 were measured for NE using high-performance liquid chromatography. Hydrocephalus caused NE levels to decrease significantly in all cortical areas. These alterations followed a rostrocaudal gradient in severity, with mean reductions of 65.8, 83.9, and 95.8% in areas 4, 22, and 17, respectively. Partial recovery occurred in animals that received shunts 16 and 17 days after kaolin injection, such that NE reductions of 75.7, 56.2, and 81.6% were noted in areas 4, 22, and 17, respectively. Shunting at 12 days after kaolin injection produced complete recovery in areas 4 and 22, with only a 67.7% decrease in area 17. These results suggest that the projection fibers from the locus ceruleus are damaged by the direct effects of hydrocephalus. Axotomy or neuropraxia of these fibers could result in decreases in NE throughout the cerebral cortex. In addition, there appears to be a period of time during which surgical decompression will allow neuropraxic fibers to recover with partial restoration of NE levels. Earlier insertion of a shunt appears to allow for more recovery than later decompression.

Topics: Animals; Animals, Newborn; Cats; Cerebral Cortex; Cerebrospinal Fluid Shunts; Disease Models, Animal; Hydrocephalus; Kaolin; Norepinephrine; Ultrasonography

Kaolin induced a clear and reproducible writhing reaction when intraperitoneally injected into mice. A simultaneous injection (i.p.) of soybean trypsin inhibitor (SBTI) significantly suppressed the kaolin-induced writhing reaction. This writhing reaction was markedly potentiated by a simultaneous injection (i.p.) of captopril. In an in vitro experiment kaolin caused kinin-release in mouse plasma, possibly through the activation of prekallikrein. This activation of plasma prekallikrein and kinin-release were inhibited in the presence of SBTI. Some non-steroidal anti-inflammatory agents inhibited the kaolin-induced writhing reaction dose-dependently. These results suggest that kaolin-induced writhing reaction may be caused by the released bradykinin through activation of the plasma kallikrein-kinin system. This model is a novel and simple tool for assessment of analgesic agents.

Topics: Acetylcholine; Analgesics; Animals; Behavior, Animal; Benzoquinones; Bradykinin; Disease Models, Animal; Kaolin; Male; Mice; Mice, Inbred ICR; Pain; Quinones

We studied the origin of the epithelioid cells (macrophages) observed in the rat brain in response to the intracisternal injection of kaolin. The rats, two days of age, were used. The animals were killed after thirteen weeks following cisternal injection of kaolin. Massive epithelioid cell-nodes with multifocal necrosis were seen in the subarachnoid space of the cerebellum, in the cerebellar parenchyma and in the fourth ventricle. They were also present in the choroid plexus. The papillary epithelioid cell-nodes were observed onto the aqueduct of Sylvius, the third and lateral ventricles. These were associated with the proliferation of the adventitia of the blood vessel in the subependymal white matter. This suggested that the vascular adventitia played a role for a formation of the epithelioid cell-node in this case. The epithelioid cell was negative in silver-stained preparation. This indicated that microglia was not a source of the epithelioid cell. Reticulin fibers were moderately increased in the lesions. The epithelioid cells phagocytized kaolin granules and gave a strong PAS-positive reaction. However, it seemed that the PAS-positive materials were not identical to the kaolin granules. A rich accumulation of apparently extra- and intracellular kaolin deposits stained metachromatically violet with toluidine blue was seen in the necrotic areas. A large number of the degenerated cells containing kaolin deposits was found especially in the marginal zone of the necrotic areas. Granulation tissue with the amount of spindle-form cells and collagen fibers was also observed in the subarachnoid space. The granulation tissue was formed by hyperplasia of fibroblasts following the proliferation of the epithelioid cells and their necrotic processes.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Brain Diseases; Cisterna Magna; Disease Models, Animal; Epithelium; Granuloma; Injections; Kaolin; Macrophages; Meningoencephalitis; Necrosis; Rats; Rats, Inbred Strains

Burn wound therapy with silver-kaolin, a topical agent applied as an aerosol spray, was evaluated in male rats given a 20 per cent total body surface area, full thickness dorsal scald burn. Burn wounds treated with silver-kaolin healed at rates comparable to untreated wounds. No significant differences were noted in the numbers or types of organisms colonizing the wounds of treated and untreated rats at 5, 12 and 19 days post-burn. To evaluate the effectiveness of silver-kaolin in treating burn wound sepsis, rats were inoculated on the wound surface with 2.5 x 10(8) Pseudomonas aeruginosa. This inoculum resulted in 100 per cent mortality in untreated rats. Rats treated with silver-kaolin had a mortality rate of 71 per cent, compared to a 9 per cent mortality rate in rats treated with 1 per cent silver sulphadiazine. When silver-kaolin was applied to the wound prior to bacterial inoculation, the mortality rate was reduced to 6 per cent. When wounds were treated with kaolin alone and then inoculated with bacteria, the mortality rate was 50 per cent, indicating that part of the effectiveness of silver-kaolin appeared to be due to a barrier effect. These results indicate that silver-kaolin may be useful for preventive topical antimicrobial therapy of acute burns or after wound debridement or excision, but is not suitable for therapy of wounds previously colonized by microorganisms.

Topics: Administration, Topical; Animals; Burns; Disease Models, Animal; Drug Combinations; Kaolin; Male; Pseudomonas Infections; Rats; Rats, Inbred Strains; Silver; Wound Healing; Wound Infection

Fourty-six cats were made hydrocephalic and hydromyelic by means of an intracisternal kaolin injection. In 17 other cats hydrocephalus and syringohydromyelia were achieved by operative occlusion of the foramina Luschkae of the fourth ventricle. In both the kaolin treated animals and the animals whose outlets of the fourth ventricles were operatively obstructed a progressive dilatation of the ventricles and central canal occurred, which could be demonstrated and followed in 30 animals by ventriculography, myelography and/or contrast filling of the hydromyelic central canal. Coinciding with the dilatation of the central canal the clinical picture of a raised intracranial pressure due to obstructive hydrocephalus improved. The presented results suggest that the dilated central canal acts as a kind of natural by-pass between the ventricles and the spinal subarachnoid space. In order to determine the role of spinal kaolin arachnoiditis on spinal cyst formation and central canal dilatation in 13 animals, kaolin was locally applied in the lower thoracic region. The local spinal kaolin arachnoiditis had no influence on central canal dilatation or cyst formation.

Topics: Animals; Cats; Cerebral Ventricles; Cerebral Ventriculography; Disease Models, Animal; Hydrocephalus; Injections, Intraventricular; Injections, Spinal; Kaolin; Myelography; Syringomyelia

A model of congenital hydrocephalus in utero in fetal lambs and rhesus monkeys has been produced by the intracisternal injection of kaolin. Initial attempts to produce hydrocephalus using silicone oil were unrewarding. Hydrocephalus had developed by 2 weeks post-injection and could be followed by ultrasonography. The pathological findings were similar to those reported using kaolin in other species. Ventriculoamniotic shunting, when successful, was capable of partially reversing the deleterious effects of hydrocephalus. The major drawback of the present model is that hydrocephalus is produced during the second rather than the first trimester of pregnancy. However, kaolin produces mainly an obstructive hydrocephalus without other associated brain or systemic anomalies.

Topics: Animals; Disease Models, Animal; Female; Fetal Diseases; Hydrocephalus; Kaolin; Macaca mulatta; Pregnancy; Sheep; Silicones; Ultrasonography

In the fetus with congenital hydrocephalus, obstruction to the flow of cerebrospinal fluid (CSF) results in ventricular dilation and neurologic impairment. Decompression of the obstructed ventricles before birth may ameliorate the damage and allow normal development to proceed. Although appealing, this pathophysiologic rationale has not been adequately tested because a satisfactory fetal model has not been available. We have developed a model of obstructive hydrocephalus in the fetal lamb and rhesus monkey by injecting kaolin into the cisterna magna through the posterior atlanto-occipital membrane early in the last trimester. Preliminary studies injecting silicone oil were unsuccessful. The development of fetal ventriculomegaly was followed using prenatal ultrasonography. Massive hydrocephalus developed in six sheep, three liveborn at term and three stillborn after premature vaginal delivery, and in 2 fetal rhesus monkeys. All treated animals had external signs of hydrocephalus with marked cranial enlargement. Neuropathologic examinations demonstrated fibrosis of the leptomeninges and subarachnoid spaces around the fourth ventricle. Dilation of the lateral and third ventricles resulted, with attenuation of the cerebral white matter. On histologic examination, the grey matter was relatively well preserved, while the white matter was severely attenuated. This model mimics the clinical and pathologic picture seen in human infants and should allow us to study the pathophysiology of congenital obstructive hydrocephalus and the efficacy and feasibility of its correction in utero.

Topics: Animals; Disease Models, Animal; Female; Hydrocephalus; Kaolin; Macaca mulatta; Pregnancy; Sheep; Silicon

The author compared the efficiency of 3-amino-4-mercapto-6-methylpyridazine (1; pyridazine S1) and some standard pharmaca by means of acute and subacute inflammation models. As evidence by the acute assay, the kaolin and carragheenin-induced oedemata of the rat paw as well as the Evans's blue excretion the potency of 1 compared with that of acetylsalicylic acid. Phenylbutazone and indomethacin exhibited a higher degree of activity. In the cotton-induced granuloma test, 1 was ineffective, whereas indomethacin applications had a powerful effect against inflammatory reactions. The results obtained during this investigation suggest that the activity spectrum of 1 is similar to that of acetylsalicylic acid.

Topics: Animals; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Carrageenan; Disease Models, Animal; Edema; Evans Blue; Exudates and Transudates; Granuloma; Indomethacin; Inflammation; Kaolin; Male; Phenylbutazone; Pyridazines; Rats; Rats, Inbred Strains

Topics: Animals; Anti-Inflammatory Agents; Arthritis, Experimental; Copper; Disease Models, Animal; Edema; Guinea Pigs; Inflammation; Kaolin; Male; Rats

The effects of kaolin-induced hydrocephalus on CSF turnover was studied in rats by ventricular perfusion and the results compared to normals. The mean CSF formation rate measured in 20 normal rats was 2.83 microliter/min. Approximately three weeks after intracisternal kaolin, the mean CSF formation rate in 17 hydrocephalic rats was reduced by 40%. CSF absorption in hydrocephalic and normal rats varied linearly with perfusion pressures between -10 and 10 cm H2O. The response of CSF absorption rate to changes in intracranial pressure was decreased in hydrocephalic rats. Ventriculomegaly of hydrocephalic rats was associated with a dilated spinal cord central canal. This suggests that kaolin hydrocephalus alters CSF pathway in rats in a manner similar to that described previously in cats and dogs. Ventriculomegaly is limited by the supporting structures of the brain because the removal of the calvarium and dura after kaolin results in massive ventriculomegaly.

Topics: Animals; Cerebrospinal Fluid; Disease Models, Animal; Hydrocephalus; Kaolin; Rats; Spinal Canal; Subarachnoid Space

The development of novel anti-inflammatory drugs (AID) has been claimed to be dependent on the discovery of models of inflammation that differ from those currently used for drug screening, e.g. carrageenen paw oedema and u.v. erythema. We have thus evaluated the effect of a variety of drugs in a number of novel models of inflammation in the rat produced in the hind paw. We have utilized kaolin, zymosan, anti-rat IgG (anti-IgG) and the Reversed Passive Arthus (RPA) reaction to produce these oedema models. We found that the non-steroidal AID's, e.g. aspirin, flufenamic acid, indomethacin, naproxen, and phenylbutazone, were active in all four tests. Of the nine novel AID examined, levamisole and tetramisole demonstrated considerable activity in all four tests and dapsone was especially active in the anti-IgG and RPA tests. In contrast, the anti-rheumatic d-penicillamine was inactive in all four models. Each of the ten compounds tested which has been claimed to influence complement function, was active in the RPA but not in the kaolin model. These results are discussed in the context of the aetiology of each oedema and the suspected mode of action of the various drugs.

Topics: Animals; Anti-Inflammatory Agents; Antibodies, Anti-Idiotypic; Arthus Reaction; Disease Models, Animal; Drug Evaluation, Preclinical; Edema; Immunoglobulin G; Kaolin; Male; Ovalbumin; Rats; Stomach Ulcer; Zymosan

Topics: Animals; Cisterna Magna; Disease Models, Animal; Endoscopy; Female; Fetal Diseases; Fetus; Hydrocephalus; Injections; Kaolin; Pregnancy; Sheep

Topics: Animals; Cisterna Magna; Disease Models, Animal; Female; Fetal Diseases; Fetus; Hydrocephalus; Injections; Kaolin; Pregnancy; Punctures; Sheep; Uterus

Adult craniectomized cats, rendered hydrocephalic by intracisternal kaolin injection, were repeatedly studied as to parameters pertaining to cerebrospinal fluid (CSF) dynamics and ventricular size. Intraventricular pressure was up to 8-fold of normal (mean 17.1 cm H2O) initially after induction of hydrocephalus and then went gradually down after 1 month. Ventricular volumes attained their maximum volume of approximately 4.5 ml at the very earliest study. The absorptive reserve (excess of absorption over formation rate of CSF) increased with time, thereby theoretically enabling the 'arrest' of the hydrocephalic process. Ventricular distensibility also increased with time, thus even the low ventricular pressure maintains the larger ventricular volume.

Topics: Animals; Cats; Cerebral Ventricles; Cerebrospinal Fluid; Dilatation, Pathologic; Disease Models, Animal; Hydrocephalus; Intracranial Pressure; Kaolin

Topics: Animals; Behavior, Animal; Disease Models, Animal; Habituation, Psychophysiologic; Humans; Kaolin; Male; Motion Sickness; Pica; Rats; Rotation; Species Specificity; Vomiting

Obstructive hydrocephlus was produced in 10-14 day-old rabbits by injection of kaolin into the cisterna magna and the ependyma and subependymal tissue was studied by electron microscopy. Generally, the study confirmed recent light microscopic observations on similar models (Torvik et al., 1976). In contrast to most previous reports, it was found that the ependyma adapted remarkably well to ventricular dilatation. No true ependymal defects occurred even in extensive hydrocephalus except at the sites of the ventricular synechiae which sometimes ruptured. The specialized ependymal junctions remained intact but outside the junctions the intercellular clefts were widened, particularly along the lateral wall of the lateral ventricle. The density of the microvilli and cilia decreased, probably because of the increase in the surface area of the ependyma. Dense bundles of filaments developed in the ependymal cells of the hydrocephalic animals. The extracellular space of the subependymal white matter appeared increased but there was no evidence of destruction of fibres or cells. Thus, the reduction of the cerebral mantle thickness was probably mainly caused by pre-sure atrophy.

Topics: Animals; Atrophy; Brain; Cilia; Cisterna Magna; Disease Models, Animal; Ependyma; Extracellular Space; Hydrocephalus; Intercellular Junctions; Kaolin; Microscopy, Electron; Rabbits

Kaolin-induced hydrosyringomyelia in dogs has been investigated by radioisotope ventriculography using both cerebrospinal fluid radioassay and scintigraphy. The hydromyelic central canal can be differentiated from the spinal subarachnoid space by scintigraphy, Serial studies show that hydromyelia arises rapidly to decompress the associated hydrocephalus in surviving animals. Syringomyelia, after a delayed onset, originates from the enlarged central canal. Radioisotope ventriculography may be a useful clinical aid in the diagnosis of hydrosyringomyelia.

Topics: Animals; Disease Models, Animal; Dogs; Kaolin; Radionuclide Imaging; Spinal Canal; Syringomyelia; Technetium; Time Factors

A quantitative model of stasis-type of venous thrombosis in rats is described. The ligated bowel loop was used after provocation by an injection of kaolin. The mesenteric vessels of the loop were cut in a dish filled with distilled water and the extinction of escaped haemoglobin was measured photometrically. Heparin was highly effective in this model. Vessel wall lesion may be used or inducing thrombosis instead of kaolin.

Topics: Acute Disease; Animals; Disease Models, Animal; Hemoglobins; Heparin; Kaolin; Ligation; Rats; Thrombophlebitis

Topics: Age Factors; Albumins; Animals; Bradykinin; Carrageenan; Consciousness; Dextrans; Disease Models, Animal; Edema; Foot; Guinea Pigs; Histamine; Inflammation; Kaolin; Methods; Mice; Povidone; Rats; Saccharomyces cerevisiae; Serotonin; Sex Factors; Species Specificity; Temperature; Time Factors

The authors present morphological findings in the brains of rabbits, dogs, cats, rats, and mice that have been used as experimental hydrocephalic models. The methods used were as follows: (1) silicone oil injection into the cisterna magna and the neighboring basal cisterns in rabbits by the method of Wisniewski; (2) kaolin administration into the cisterna magna in rabbits and dogs (Dixon); (3) ballooning method with Foley's catheter into the 4th ventricle in rabbits (Milho-rat); (4) plug formation with small pieces of laminalia into the cisterna magna in rabbits by our method; (5) Hy-3 hereditary hydrocephalic mouse bred by Gruenberg; (6) ligation of the placental vessels of the pregnant rat at 13 days of gestation by our method, and (7) transplacental intraperitoneal administration of ethylnitrosourea in a pregnant rat at 9.5 days of gestation. The models with silicone oil, kaolin, laminalia, and ballooning methods produced obstructive hydrocephalus with various grades of ventricular dilatation. The models with the ethylnitrosourea-induced method, ligation of placental vessels, and Hy-3 mouse produced prenatal hydrocephalus. Dilatation of the ventricular system and histological abnormalities do not occur as a uniform process.

Topics: Animals; Cats; Disease Models, Animal; Dogs; Ethylnitrosourea; Hydrocephalus; Kaolin; Methods; Mice; Rabbits; Rats; Silicones

Topics: Animals; Cats; Cerebral Ventricles; Cerebral Ventriculography; Cerebrospinal Fluid Shunts; Craniotomy; Disease Models, Animal; Dura Mater; Humans; Hydrocephalus; Kaolin; Postoperative Complications; Recurrence; Temporal Bone

Topics: Absorption; Animals; Cats; Cerebral Ventricles; Cerebrospinal Fluid; Disease Models, Animal; Hydrocephalus; Intracranial Pressure; Kaolin; Perfusion; Sacrum; Serum Albumin, Radio-Iodinated; Spinal Cord; Subarachnoid Space

Topics: Absorption; Animals; Brain; Cats; Cerebrospinal Fluid; Cisterna Magna; Disease Models, Animal; Elasticity; Hydrocephalus; Intracranial Pressure; Kaolin

Topics: Absorption; Animals; Cats; Cerebral Ventricles; Choroid Plexus; Disease Models, Animal; Hydrocephalus; Intracranial Pressure; Kaolin; Perfusion

Topics: Adolescent; Arnold-Chiari Malformation; Brain Diseases; Cerebral Ventriculography; Cerebrospinal Fluid Shunts; Child; Child, Preschool; Disease Models, Animal; Female; Humans; Hydrocephalus; Intracranial Pressure; Kaolin; Male; Skull; Synostosis

Topics: Cerebral Ventricles; Cerebrospinal Fluid Shunts; Child, Preschool; Disease Models, Animal; Female; Humans; Hydrocephalus; Infant, Newborn; Infant, Newborn, Diseases; Intracranial Pressure; Kaolin; Male; Prognosis; Serum Albumin, Radio-Iodinated

Topics: Animals; Cats; Cerebral Ventricles; Cerebrospinal Fluid; Disease Models, Animal; Dura Mater; Hydrocephalus; Intracranial Pressure; Kaolin; Perfusion; Skull

Topics: Animals; Arachnoiditis; Brain; Brain Stem; Cerebrospinal Fluid Shunts; Disease Models, Animal; Dogs; Female; Hydrocephalus; Kaolin; Spinal Cord; Subarachnoid Space

Topics: Animals; Anthelmintics; Anti-Inflammatory Agents; Arthritis; Disease Models, Animal; Dracunculiasis; Edema; Imidazoles; Kaolin; Niridazole; Pleurisy; Rats; Thiazoles; Turpentine

Topics: Adrenocorticotropic Hormone; Aminopyrine; Animals; Anti-Inflammatory Agents; Aspirin; Carrageenan; Dextrans; Dimethyl Sulfoxide; Disease Models, Animal; Edema; Flufenamic Acid; Formaldehyde; Granuloma; Indomethacin; Inflammation; Kaolin; Male; Mefenamic Acid; Ovalbumin; Oxyphenbutazone; Phenylbutazone; Prednisolone; Rats; Sodium Salicylate; Trypsin

Topics: Aniline Compounds; Animals; Anti-Inflammatory Agents; Asbestos; Dextrans; Disease Models, Animal; Drug Combinations; Edema; Evaluation Studies as Topic; Female; Formaldehyde; Granuloma; Indomethacin; Inflammation; Kaolin; Phenylbutazone; Prednisolone; Rats; Rats, Inbred Strains; Salicylates; Serotonin; Sodium Salicylate

Topics: Animals; Arthritis; Arthus Reaction; Bradykinin; Capillary Permeability; Carrageenan; Depression, Chemical; Dextrans; Disease Models, Animal; Dogs; Edema; Exudates and Transudates; Female; Formaldehyde; Granuloma; Guinea Pigs; Histamine; Hyaluronoglucosaminidase; Kaolin; Lymph; Male; Mice; Mycobacterium Infections; Ovalbumin; p-Methoxy-N-methylphenethylamine; Phytotherapy; Plants, Medicinal; Rabbits; Rats; Serotonin; Species Specificity; Swine