myelin-basic-protein and Brain-Diseases

We report here an infant with 18q deletion syndrome, and intractable apneic seizures. He had intrauterine growth retardation and dysmorphic features. Chromosomal analysis demonstrated mosaicism of 18q interstitial deletion (q12.3-q22.3). From the age of 3 months, apneic attacks occurred from once a week to over 10 times a day despite many oral antiepileptic agents, and were diagnosed as complex partial seizures. Ictal electroencephalogram and 18F-fluorodeoxyglucose-positron emission tomography at the age of 10 months identified the epileptic focus in the right parieto-temporal region. He also had severe psychomotor retardation. Head MRI examination revealed diffuse cerebral atrophy and severe white matter dysmyelination, which was caused by the deletion of myelin basic protein gene at the locus of 18q22.3. This locus may be responsible for the clinical manifestations of 18q deletion syndrome. Detailed description of the onset, seizure types, and prognosis of epilepsy associated with 18q deletion syndrome is rare. It was suggested that the locus of 18q21.3-q22.3 was responsible for autonomic seizures in 18q deletion syndrome.

Topics: Apnea; Brain Diseases; Chromosome Deletion; Chromosomes, Human, Pair 18; Demyelinating Diseases; Epilepsy, Complex Partial; Gene Deletion; Humans; Infant; Infant, Newborn; Male; Myelin Basic Protein; Syndrome

A previously healthy 19-month-old boy developed acute encephalopathy, thrombocytopenia and hepatic dysfunction. Human herpesvirus-6 (HHV-6) DNA was found in his CSF during the acute stage of the disease by means of the polymerase chain reaction. T2-weighted MRI revealed high signal intensity in the left thalamus and left parieto-occipital deep white matter. The myelin basic protein concentration in the CSF was elevated suggesting acute demyelination. The patient is now 2.5 years old and has no sequelae.. Since clinical course and neuroimaging after HHV-6 infection are similar to those in acute disseminated encephalomyelitis, clinicians must pay attention to primary HHV-6 infection in patients under 2 years old with white matter lesions.

Topics: Acute Disease; Brain; Brain Diseases; Child, Preschool; Demyelinating Diseases; DNA, Viral; Dominance, Cerebral; Encephalitis, Viral; Follow-Up Studies; Herpesviridae Infections; Herpesvirus 6, Human; Humans; Infant; Liver Function Tests; Magnetic Resonance Imaging; Male; Myelin Basic Protein

We investigated dexamethasone therapy for preventing delayed encephalopathy after carbon monoxide (CO) poisoning. Eighty healthy male rats were exposed to CO and randomly divided into four groups: hyperbaric oxygen treatment (H), treatment (D), combined hyperbaric and dexamethasone treatment (C), and a control (M) group in which the rats inhaled CO to coma in the hyperbaric oxygen chamber, then were removed without further treatment. Twelve rats were put into the hyperbaric oxygen chamber and treated with air for 60 min (N) group. An eight arm maze was used to evaluate cognitive and memory abilities of these mice. Serum myelin basic protein (MBP) levels were evaluated using ELISA, and magnetic resonance imaging was used to observe brain demyelination and morbidity associated with delayed encephalopathy. A sample of the hippocampus from each group was examined by light microscopy. Cognitive and memory functions decreased in the control group M. Three days after CO poisoning, the serum MBP level of each group increased significantly. On Day 10 after CO poisoning, the MBP levels in groups C and D decreased significantly, but returned to normal on Day 18. MBP levels in the M and H groups were elevated at all time points. Brain MRIs showed significant differences among C, D, H and control M groups. Hematoxylin & eosin staining of the hippocampus showed greater damage in the control M and H groups. Early dexamethasone treatment may be useful for preventing delayed encephalopathy after CO poisoning and may reduce serum MBP levels.

Topics: Animals; Anti-Inflammatory Agents; Brain Diseases; Carbon Monoxide Poisoning; Cognition; Combined Modality Therapy; Dexamethasone; Hippocampus; Hyperbaric Oxygenation; Male; Memory; Myelin Basic Protein; Rats; Rats, Wistar; Treatment Outcome

We aimed to investigate the potential mechanism (s) of delayed encephalopathy after acute carbon monoxide (CO) poisoning in rats, and the effect of dexamethasone on this process. A delayed encephalopathy animal model was generated by intraperitoneal injection of CO into Wistar rats. Normal rats were sent as a control group, and poisoning rats were randomly separated into two groups treated with vehicle and dexamethasone respectively. The rat behavior was evaluated by Morris water maze. The level of myelin basic protein (MBP), myeloperoxidase (MPO) expression in the serum and hippocampus of experimental rats was measured using enzyme-linked immunosorbent assay (ELISA) and immunohisto chemistry. The latency to find the platform was significantly increased by dexamethasone treatment for rats after poisoning at day 7 and 14. MBP serum concentration in the vehicle treatment group was significantly higher than that in rats injected with dexamethasone following poisoning at 90 min, 7d, 14d, 21d. Moreover, MPO concentration was higher at day 14 after poisoning as well. In addition, MBP expression was down regulated in the poisoning group, which was nearly reversed at control level in the dexamethasone group. Inflammation plays a key role in delayed encephalopathy of rats induced by acute CO intoxication, which could be attenuated by dexamethasone via protecting myelin from damage of inflammation response.

Topics: Animals; Brain Diseases; Carbon Monoxide Poisoning; Dexamethasone; Male; Maze Learning; Myelin Basic Protein; Peroxidase; Rats; Rats, Wistar

A diagnostic feature of focal cortical dysplasia (FCD) type II on magnetic resonance imaging (MRI) is increased subcortical white matter (WM) signal on T2 sequences corresponding to hypomyelination, the cause of which is unknown. We aimed to quantify WM pathology in FCD type II and any deficiency in the numbers and differentiation of oligodendroglial (OL) cell types within the dysplasia.. In 19 cases we defined four regions of interests (ROIs): ROI1 = abnormal WM beneath dysplasia, ROI2 =dysplastic cortex, ROI3 = normal WM, and ROI4 = normal cortex. We quantified axonal and myelin density using immunohistochemistry for neurofilament, myelin basic protein and quantified mature OL with NogoA, cyclic nucleotide 3-phosphodiesterase (CNPase) and OL precursor cell (OPC) densities with platelet derived growth factor receptor (PDGFR)α, β and NG-2 in each region.. We observed a significant reduction in myelin and axons in the WM beneath dysplasia relative to normal WM and there was a correlation between relative reduction of myelin and neurofilament in each case. OL and OPC were present in the WM beneath dysplasia and although present in lower numbers with most markers, were not significantly different from normal WM. Neurofilament and myelin labeling highlighted disorganized orientation of fibers in dysplastic cortex but there were no significant quantitative differences compared to normal cortex. Clinical correlations showed an association between the severity of reduction of myelin and axons in the WM of FCD and duration of epilepsy.. These findings indicate a reduction of myelinated axons in the WM of FCD type II rather than dysmyelination as the primary pathologic process underlying WM abnormalities, possibly influenced by duration of seizures. The range of OPC to OL present in FCD type II does not implicate a primary failure of cell recruitment and differentiation of these cell types in this pathology.

Topics: 2',3'-Cyclic-Nucleotide Phosphodiesterases; Adolescent; Adult; Aged; Antigens; Brain; Brain Diseases; Child; Epilepsy; Female; Humans; Leukocyte Common Antigens; Magnetic Resonance Imaging; Male; Malformations of Cortical Development; Malformations of Cortical Development, Group I; Middle Aged; Myelin Basic Protein; Myelin Proteins; Nerve Fibers, Myelinated; Nerve Tissue Proteins; Neural Pathways; Nogo Proteins; Oligodendroglia; Proteoglycans; Receptor, Platelet-Derived Growth Factor alpha; Statistics, Nonparametric; Young Adult

Pancreatic encephalopathy (PE) is a severe complication and significant cause of death in patients with severe acute pancreatitis (SAP). We have reported previously that low-molecular-weight heparin (LMWH) treatment could reduce incidence of PE in SAP patients. Our objective here was to investigate the protective effect of LMWH and its mechanism on PE in SAP rats.. SD rats were randomly divided into three groups: (1) Sham-operation (S) group, (2) SAP group, and (3) LMWH treatment (LMWH) group. LMWH was administrated 4 h after the SAP model conducted. The levels of serum amylase, myelin basic protein (MBP), tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6), brain water content, occurrence of apoptosis, and pathological changes of pancreas and brain were measured at 1 day after models were set up in the SAP and S groups, and 1 day after LMWH treatment was administrated in the LMWH group.. (1) The levels of serum amylase, TNF-α, and IL-6 in the SAP group were increased significantly more than those in the S and LMWH groups (all P < 0.001), as were the levels of serum MBP in the SAP group compared to those in the S and LMWH groups (P < 0.01, <0.05 respectively). However, while the level of serum amylase and IL-6 in the LMWH group were significantly increased compared to those in the S group (P < 0.05, <0.001 respectively), the levels of TNF-α and MBP showed no significant difference between the LMWH and S groups (all P > 0.05). (2) The brain water content in the SAP group was significantly increased compared to the S group and LMWH group (P < 0.01, <0.05 respectively). (3) Neuronal apoptosis, demyelination, and mitochondrial vacuolation in neuronal cells were observed in the SAP group; in contrast, in the LMWH group, significantly lower rates of neuronal apoptosis, demyelination and mitochondrial edema were observed in neuronal cells.. The protective effect of LMWH on PE progression in SAP rats might result from inhibition of inflammatory activation and reduction of the occurrence of neuronal apoptosis.

Topics: Amylases; Animals; Anti-Inflammatory Agents; Apoptosis; Brain; Brain Diseases; Heparin, Low-Molecular-Weight; Interleukin-6; Microscopy, Electron, Transmission; Myelin Basic Protein; Neurons; Pancreatitis; Rats; Rats, Sprague-Dawley; Tumor Necrosis Factor-alpha; Water

Periventricular leukomalacia (PVL), a common neonatal brain white matter (WM) lesion, is frequently associated with cerebral palsy. Growing evidence has indicated that in addition to ischemia/reperfusion injury, cytokine-induced brain injury associated with maternal or fetal infection may also play an important role in the pathogenesis of PVL. Recent studies have shown that administration of lipopolysaccharide (LPS) to pregnant rats causes enhanced expression of the cytokines, i.e., IL-1 beta, TNF-alpha, and IL-6, in fetal brains. In recent years, it has been shown that erythropoietin (EPO) has a critical role in the development, maintenance, protection and repair of the nervous system. In the present study we investigated the effect of EPO on LPS-induced WM injury in Sprague-Dawley rats. LPS (500 microg/kg) suspension in pyrogen-free saline was administered intraperitoneally to pregnant rats at 18 and 19 days of gestation. The control group was treated with pyrogen-free saline. They were given 5,000 U/kg recombinant human EPO. Seven-day-old Sprague-Dawley rat pups were divided into four groups: control group, LPS-treated group, prenatal maternal EPO-treated group (5,000 U/kg, intraperitoneally given to pregnant rats at 18 and 19 days of gestation), and postnatal EPO-treated group (5,000 U/kg, intraperitoneally given to 1-day-old rat pups). Cytokine induction in the postnatal 7-day-old (P7) rat brain after maternal administration of LPS was determined by the ELISA method. The proinflammatory cytokine levels (IL-1 beta, TNF-alpha, and IL-6) in P7 rat pup brains were significantly increased in the LPS-treated group as compared with the control group. Prenatal maternal EPO treatment significantly reduced the concentration of TNF-alpha and IL-6 in the newborn rat brain following LPS injection. The concentration of IL-1 beta was decreased in the intrauterine EPO treatment group. Postnatal EPO treatment significantly decreased only the IL-6 concentration in the newborn rat brain following LPS injection. The concentration of cytokines, IL-1 beta and TNF-alpha, was reduced in the postnatal EPO treatment group. We demonstrated here that LPS administration in pregnant rats at gestational day 18 and 19 induced WM injury in P7 progeny characterized by apoptosis. Prenatal maternal and postnatal EPO treatment significantly reduced the number of apoptotic cells in the periventricular WM. Using immunohistochemistry techniques, we investigated the effects of maternal admi

Topics: Animals; Animals, Newborn; Apoptosis; Bacterial Infections; Brain; Brain Diseases; Disease Models, Animal; Erythropoietin; Female; Humans; Infant, Newborn; Interleukin-1beta; Interleukin-6; Leukomalacia, Periventricular; Lipopolysaccharides; Myelin Basic Protein; Pregnancy; Random Allocation; Rats; Rats, Sprague-Dawley; Tumor Necrosis Factor-alpha

The mechanisms leading to CNS disorders after EBV infections are unclear. We report the case of a patient who developed a severe, but reversible, encephalopathy following an infectious mononucleosis. We detected no EBV DNA in the blood or in the cerebrospinal fluid (CSF) and no EBV-specific antibodies in the CSF. However, we found a potent MOG-specific cellular and humoral immune response. Interestingly, MOG-specific cellular immune response rapidly decreased, paralleling the improvement of clinical condition. In conclusion, this detailed study shows that acute EBV infection can trigger a potent auto-inflammatory response in the CNS, without evidence of an overt infection.

Topics: Adult; Antibodies; Brain Diseases; Cell Proliferation; Disease Progression; Enzyme-Linked Immunosorbent Assay; Epstein-Barr Virus Infections; Herpesvirus 4, Human; Humans; Interferon-gamma; Male; Myelin Basic Protein; Myelin Proteins; Myelin-Associated Glycoprotein; Myelin-Oligodendrocyte Glycoprotein

Diffusion tensor magnetic resonance imaging (DT-MRI) was applied for in vivo quantification of myelin loss and regeneration. A transgenic mouse line (Oligo-TTK) expressing a truncated form of the herpes simplex virus 1 thymidine kinase gene (hsv1-tk) in oligodendrocytes was studied along with two induced phenotypes of myelin pathology. Myelin loss and axonal abnormalities differentially affect values of DT-MRI parameters in the brain of transgenic mice. Changes in the anisotropy of the white matter were assessed by calculating and mapping the radial (D perpendicular) and axial (D parallel) water diffusion to axonal tracts and fractional anisotropy (FA). A significant increase in D perpendicular attributed to the lack of myelin was observed in all selected brain white matter tracts in dysmyelinated mice. Lower D parallel values were consistent with the histological observation of axonal modifications, including reduced axonal caliber and overexpression of neurofilaments and III beta-tubulin. We show clearly that myelination and axonal changes play a role in the degree of diffusion anisotropy, because FA was significantly decreased in dysmyelinated brain. Importantly, myelin reparation during brain postnatal development induced a decrease in the magnitude of D( perpendicular) and an increase in FA compared with the same brain before recovery. The progressive increase in D parallel values was attributed to the gain in normal axonal morphology. This regeneration was confirmed by the detection of enlarged oligodendrocyte population, newly formed myelin sheaths around additional axons, and a gradual increase in axonal caliber.

Topics: Animals; Animals, Newborn; Anisotropy; Antiviral Agents; Brain; Brain Diseases; Brain Mapping; Demyelinating Diseases; Diffusion Magnetic Resonance Imaging; Ganciclovir; Image Processing, Computer-Assisted; Immunohistochemistry; Mice; Mice, Transgenic; Microscopy, Electron, Transmission; Myelin Basic Protein; Nerve Fibers, Myelinated; Oligodendroglia; Protein Serine-Threonine Kinases; Protein-Tyrosine Kinases; Recovery of Function; Time Factors

To investigate the protective effects of allopurinol (ALLO) on white matter damage in premature rats.. An animal model for white matter damage was established by bilateral carotid artery occulation (BCAO). Eighty-four newborn SD rats (1 day old) were used in this study and were divided randomly into three groups [sham surgery (Sham); BCAO group (BCAO); allopurinol-treated group (ALLO)]. Pathological changes were studied 7 days and 14 days after BCAO, respectively. Myelin basic protein (MBP) was detected by immunohistochemistry 7 days and 14 days after BCAO, respectively. MBP-mRNA expression was determined 7 days and 14 days after BCAO respectively by reverse transcription-polymerase chain reaction (RT-PCR) with fluorescent quantitative method.. In BCAO group, mild or severe rarefaction was found in 10 cases in the corpus callosum area, especially at the cingulum. Pathological changes of white matter were found in 4 cases in internal capsule. Subcortex white matter rarefaction was found in 8 cases. The extent of white matter rarefaction in ALLO group was reduced significantly. Enlargement of bilateral ventricles was found in 6 of 8 cases in BCAO group. The average ventricle size in ALLO group (2.44 +/- 0.71)% was reduced significantly as compared with that in BCAO group (3.27 +/- 0.73)% (P < 0.05). Strong MBP positive staining was found in sub-cortex, corpus callosum, hippocampus gyrus, and internal capsule of P14 sham surgery group. In BCAO group the MBP staining extent was reduced. The extent of MBP staining of ALLO group was between the other two groups. The optical density (OD) of MBP positive staining in BCAO group (6.60 +/- 0.68) was found higher than that in sham surgery group (9.40 +/- 0.53), the difference was statistically significant (P < 0.05). Compared with BCAO group, OD value in ALLO group (7.10 +/- 0.18) increased significantly (P < 0.05). RT-PCR data showed that MBP-mRNA copies (log10) in P7 and P14 rats of both BCAO and ALLO groups were lower than that in sham surgery group (P < 0.01); However, MBP-mRNA copies in ALLO group were higher than that in BCAO group (P < 0.05).. BCAO could be used in newborn rats (1 day old) to establish a premature white matter damage (WMD) animal model. Allopurinol may have a potential protective effect on premature SD rat with ischemic WMD.

Topics: Allopurinol; Animals; Animals, Newborn; Brain; Brain Diseases; Disease Models, Animal; Immunohistochemistry; Myelin Basic Protein; Random Allocation; Rats; Rats, Sprague-Dawley; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger

Cytomegalovirus (CMV) is the most common opportunistic viral pathogen associated with HIV/AIDS or immunosuppressive therapy. Systemic pathology may be caused either through direct virus-mediated infection or by indirect mechanisms such as 'by-stander' apoptosis. CMV infection of the central nervous system (CNS) occurs late in disease progression and understanding of pathology in the brain is fundamental for selection of appropriate therapies.. Using a model of disseminated neurotropic CMV disease, these experiments are designed to identify cellular predilection of murine CMV (MCMV) within mature brain and to determine, if CMV induces apoptosis within CNS cells.. Adult immunodeficient (SCID) and normal BALB/c mice were infected via the tail vein with 4.5 x 10(5)pfu recombinant MCMV expressing a green fluorescent protein reporter. Animals were perfused at various time periods from 3 to 35 days post inoculation and tissues were stained for MCMV, GFAP, NEU-N, MBP, TUNEL, and caspase-3.. CMV infection within brain was observed in multiple, independent foci affecting several different cell types, including neurons, glial cells, meninges, ependymal cells, and cerebral vessels. Cellular changes included nuclear karyopyknosis and karyorrhexis, and associated meningitis, choroiditis, encephalitis, vasculitis, and necrosis. TUNEL and caspase-3 staining of brain-demonstrated apoptosis of nearby 'by-stander' meningial, glial, and neuronal cells, but only in immunodeficient mice lacking T- and B-lymphocytes. Generally, only large CMV infection foci were associated with apoptosis of non-infected adjacent cells.. These results indicate that MCMV may cause both direct and indirect pathology to brain and that T-cell independent apoptosis of surrounding cells of the CNS may be an important mechanism of disease in the pathogenesis of neurotropic CMV.

Topics: Animals; Apoptosis; Brain; Brain Diseases; Caspase 3; Caspases; Cytomegalovirus; Cytomegalovirus Infections; Female; Glial Fibrillary Acidic Protein; Immunocompromised Host; In Situ Nick-End Labeling; Mice; Mice, Inbred BALB C; Mice, SCID; Myelin Basic Protein; Severe Combined Immunodeficiency; T-Lymphocytes

Ischemia/reperfusion injury to the developing brain is a major cause of neurologic abnormalities in preterm infants. To investigate the underlying mechanisms, we modified a previously described rat model of unilateral uterine-artery ligation on the 17th embryonic day (E17). Growth retardation was taken as an index of in utero ischemia, and pups born with a birth weight more than 2 standard deviations below that of controls were compared with the same-litter, normal-growth control pups born from the nonligated horn. Prenatal ischemia probably associated with hypoxia and followed by reperfusion at birth induced white matter damage at a developmental stage corresponding to extreme prematurity in humans. On P0 (day of birth), growth-retarded pups exhibited lesions in the cingular white matter and internal capsule with increased counts of activated microglial cells for 2 weeks compared with controls. Astrogliosis was detected in the injured white matter. On P3, increased apoptotic cell death was seen in O4-positive preoligodendrocytes, which were abnormally scarce on P7. Defective myelination, as assessed by myelin-binding-protein labeling, was detected until adulthood. The diffuse white matter damage in growth-retarded rats replicated the main features of white matter damage in human preterm infants.

Topics: Animals; Animals, Newborn; Brain Diseases; Caspase 3; Caspases; CD11b Antigen; Cell Count; Cell Death; Disease Models, Animal; Embryo, Mammalian; Female; Gene Expression Regulation, Developmental; Glial Fibrillary Acidic Protein; Glucose Transporter Type 2; Hypoxia-Ischemia, Brain; Immunohistochemistry; In Situ Nick-End Labeling; Male; Myelin Basic Protein; Neovascularization, Pathologic; O Antigens; Plant Lectins; Pregnancy; Rats; Rats, Sprague-Dawley; Statistics, Nonparametric

Levodopa, the major treatment for patients with Parkinson's disease, has been shown to induce a variety of compensatory effects, including facilitation of sprouting by dopaminergic neurons, in experimental animals with lesions leading to denervation of the striatum. To better understand the cellular and molecular environment where most of these compensatory changes take place, in particular elements that might contribute to the recovery of dopaminergic innervation, we have constructed a differential expression library enriched in transcripts from the striata of rats with lesions of the medial forebrain bundle treated with levodopa for 6 months. We have used this library to screen an expression array of rat genes representing the major cell functions, and have identified several that are involved in neurotrophic mechanisms and plasticity. We have confirmed the differential expression of selected transcripts by non-radioactive in situ hybridization, and report that the growth factor pleiotrophin, myelin basic protein and calmodulin are overexpressed in the denervated striatum of levodopa-treated rats.

Topics: Animals; Antiparkinson Agents; Behavior, Animal; Brain Diseases; Calmodulin; Carrier Proteins; Cell Count; Corpus Striatum; Cytokines; Dopamine Plasma Membrane Transport Proteins; Female; Functional Laterality; Gene Expression; Gene Library; Immunohistochemistry; In Situ Hybridization; Levodopa; Membrane Glycoproteins; Membrane Transport Proteins; Myelin Basic Protein; Nerve Tissue Proteins; Oligonucleotide Array Sequence Analysis; Oxidopamine; Radioimmunoassay; Rats; Rats, Wistar; Substantia Nigra

Pigmentary type of orthochromatic leukodystrophy (POLD) is an adult-onset leukodystrophy, characterized pathologically by the presence of glial and microglial cytoplasmic pigment inclusions. The complete phenotype, genotype and pathogenetic mechanisms in POLD have not been elucidated. We followed for 18 years a woman with autopsy-proven POLD, who presented with 'frontal' dementia and spasticity. Her further course was marked by progressive mutism, apraxia and seizures. Her sister had died of the same disease after a much more rapidly progressing course. These sisters had primary infertility with pathologic evidence of streak ovaries. Diagnosis was confirmed in both cases by post-mortem examination. POLD is a rare cause of adult-onset leukodystrophy presenting with dementia. Ovarian dysgenesis is extremely rare in the absence of demonstrable chromosomal abnormalities and extends the clinical spectrum of POLD.

Topics: Adult; Brain; Brain Diseases; Demyelinating Diseases; Female; Humans; Immunohistochemistry; Microscopy, Electron; Middle Aged; Myelin Basic Protein; Myelin Proteolipid Protein; Ovary; Pedigree

The 4e transgenic mouse is characterized by overexpression of the PLP gene. Heterozygous littermates containing three PLP gene copies develop and myelinate normally. However, a progressive CNS demyelination begins at 3-4 months of age. Despite focal demyelination, these animals survive for one year with hind limb paralysis. We used this CNS demyelination model to determine if grafts of CG4 oligodendrocyte progenitors would survive and myelinate the adult CNS. Either CG4 cells, or co-grafts of CG4/B 104 cells 11:1 ratio respectively) were performed. Grafted cells survived and migrated in the normal and transgenic brain. Non-treated transgenic animals revealed extensive lack of myelin. Three months post-transplant hosts with CG4 or co-transplants displayed a near normal myelin pattern. Double immunofluorescence for neurofilament and myelin basic protein revealed the presence of many naked axons in non-grafted transgenic animals. Those grafted with progenitor CG4 cells or cografts displayed a clear increase in remyelination. This data provides a new direction for the development of cell replacement therapies in demyelinating diseases.

Topics: Animals; Brain Diseases; Cell Line; Cell Movement; Cell Survival; Demyelinating Diseases; Fluorescent Antibody Technique, Direct; Immunohistochemistry; Mice; Mice, Transgenic; Myelin Basic Protein; Myelin Sheath; Oligodendroglia; RNA, Messenger; Stem Cell Transplantation; Stem Cells; Transferrin

Poliovirus replicon vectors transiently express foreign proteins selectively in motor neurons of the anterior horn of the spinal cord. Here we intraspinally inoculated mice transgenic for the poliovirus receptor (PVR) with replicons encoding murine tumor necrosis factor alpha (mTNF-alpha). We detected high-level expression of mTNF-alpha in the spinal cords of these animals at 8-12 h post inoculation; this returned to background by 72 h. The mice exhibited ataxia and tail atony, whereas animals given a replicon encoding green fluorescent protein (GFP) exhibited no neurological symptoms. Histology of spinal cords from mice given the replicon encoding mTNF-alpha revealed neuronal chromatolysis, reactive astrogliosis, decreased expression of myelin basic protein, and demyelination. These animals recovered with only slight residual damage. This study shows that replicon vectors have potential for targeted delivery of therapeutic proteins to the central nervous system and provide a new approach for treatment of spinal cord trauma and neurological disease.

Topics: Animals; Astrocytes; Brain Diseases; Central Nervous System Diseases; Cytokines; Gene Transfer Techniques; Genetic Therapy; Green Fluorescent Proteins; HeLa Cells; Humans; Immunohistochemistry; Luminescent Proteins; Membrane Proteins; Mice; Mice, Transgenic; Microglia; Models, Genetic; Motor Neurons; Myelin Basic Protein; Myelin Sheath; Oligodendroglia; Poliovirus; Promoter Regions, Genetic; Receptors, Virus; Spinal Cord; Time Factors; Transduction, Genetic; Tumor Necrosis Factor-alpha

Brain-derived neurotrophic factor (BDNF) has potent effects on neuronal survival and plasticity during development and after injury. In the nervous system, neurons are considered the major cellular source of BDNF. We demonstrate here that in addition, activated human T cells, B cells, and monocytes secrete bioactive BDNF in vitro. Notably, in T helper (Th)1- and Th2-type CD4(+) T cell lines specific for myelin autoantigens such as myelin basic protein or myelin oligodendrocyte glycoprotein, BDNF production is increased upon antigen stimulation. The BDNF secreted by immune cells is bioactive, as it supports neuronal survival in vitro. Using anti-BDNF monoclonal antibody and polyclonal antiserum, BDNF immunoreactivity is demonstrable in inflammatory infiltrates in the brain of patients with acute disseminated encephalitis and multiple sclerosis. The results raise the possibility that in the nervous system, inflammatory infiltrates have a neuroprotective effect, which may limit the success of nonselective immunotherapies.

Topics: Autoantigens; B-Lymphocytes; Brain Diseases; Brain-Derived Neurotrophic Factor; Encephalitis; Glycoproteins; Humans; Inflammation; Lymphocyte Activation; Monocytes; Multiple Sclerosis; Myelin Basic Protein; Neurodegenerative Diseases; Oligodendroglia; RNA, Messenger; T-Lymphocytes; Transcription, Genetic

Topics: Brain; Brain Diseases; Chromosome Deletion; Chromosomes, Human, Pair 18; Demyelinating Diseases; Humans; Magnetic Resonance Imaging; Myelin Basic Protein; Syndrome

Topics: Brain; Brain Diseases; Chromosome Deletion; Chromosomes, Human, Pair 18; Demyelinating Diseases; Humans; Magnetic Resonance Imaging; Myelin Basic Protein; Syndrome

Because of an association of human neuroborreliosis with the development of an antibody response against an antigen in neural tissue that cross-reacts with an epitope on the flagellin protein of Borrelia burgdorferi, C3H transgenic mice were created that expressed the flagellin epitope (amino acids 213-224) as a fusion protein with myelin basic protein. The transgenic mice expressed the flagellin epitope selectively in myelinated regions of the nervous system. Both transgenic and non-transgenic mice developed an antibody response to the flagellin epitope during B. burgdorferi infection and both developed arthritis and carditis. However, no lesions were found in the central nervous system of either type of mouse for up to 8 weeks after infection. The data indicate that expression of the flagellin 213-24 epitope in mice does not result in neurologic disease, suggesting that B. burgdorferi flagellin antibodies may not be directly implicated in neuroborreliosis.

Topics: Animals; Brain Diseases; Cross Reactions; Epitopes; Female; Flagellin; Humans; Lyme Disease; Mice; Mice, Inbred C3H; Mice, Transgenic; Myelin Basic Protein

Tuberous sclerosis (TSC) is an autosomal dominant syndrome that is linked to two genetic loci: TSC1 (9q34) and TSC2 (16p13). Brain manifestations such as cortical tubers and subependymal hamartoma/giant cell astrocytomas are major causes of TSC-related morbidity. In this study, we describe the central nervous system involvement in a unique rodent model of tuberous sclerosis. The Eker rat carries a spontaneous germline mutation of the TSC2 gene and is predisposed to multiple neoplasia. In a series of 45 adult Eker carriers (TSC2 +/-), three types of focal intracranial lesions were found, of which the subependymal and subcortical hamartomas were most prevalent (65%). There exist remarkable phenotypic similarities between the Eker rat and human subependymal lesions. Our study indicates that the predominant cellular phenotype of the subependymal hamartomas is astroglial and suggests that the neuronal contribution within these lesions is, in part, the result of pre-existing myelinated axons. The hamartomas did not show evidence of loss of the wild-type TSC2 allele; it remains to be determined whether TSC2 inactivation is necessary for their pathogenesis. This genetically-defined rodent model may be useful in elucidating the molecular and developmental basis of the subependymal giant cell astrocytoma in humans.

Topics: Animals; Astrocytes; Brain Diseases; Calbindins; Disease Models, Animal; Ependyma; Glial Fibrillary Acidic Protein; Hamartoma; Immunohistochemistry; Loss of Heterozygosity; Myelin Basic Protein; Neurofilament Proteins; Rats; Rats, Inbred F344; Rodent Diseases; S100 Calcium Binding Protein G; Tuberous Sclerosis; Tubulin

A total of 21 patients with postmeasles and 26 patients with postvaricella C.N.S. complications were studied. In both groups, males were predominant than females. The C.N.S. manifestations included disturbed level of consciousness, coma, seizures, motor deficits, ataxia and myoclonus. The sequelae were more frequent in postmeasles cases and ranged from behavioral abnormalities to motor deficits. C.S.F. examination showed that most of the cases demonstrated increase in the protein content (45-100mg) and pleocytosis. Myelin protein was detected in 8 samples and 6 samples of postmeasles and varicella C.S.F. out of 12 samples in Tested in each group. Specific virus IgG antibody was detected significantly in 8 paired C.S.F. samples of postvaricella group and only one sample of postmeasles out of 12 paired samples tested in each group. C-T. scan examination revealed that the most common finding was the brain oedema (13 in measles, and 21 in varicella group).

Topics: Adolescent; Adult; Brain Diseases; Brain Edema; Chickenpox; Child; Female; Humans; Immunoglobulin A; Immunoglobulin G; Immunoglobulin M; Male; Measles; Myelin Basic Protein; Serum Albumin

Myelin basic protein (MBP) in the cerebrospinal fluid (CSF) of patients with brain tumors and other neurological diseases was measured before, during and after various treatments such as surgery, chemotherapy and irradiation. We assessed the significance of changes in the MBP levels during the course of treatment, and speculate on what the elevated level of MBP in brain tumor patients indicates. In meningeal dissemination of malignant tumors, meningeal carcinomatosis from cancer of the systemic organ showed the highest level of MBP followed by meningeal gliomatosis and meningeal lymphoma. Meningeal carcinomatosis and meningeal lymphoma, which have responded to chemotherapy, showed normal levels of MBP after chemotherapy. Six of eight patients with newly diagnosed malignant glioma showed moderate to high levels of MBP (range 4.6-35.5ng/ml) just before intraarterial chemotherapy with VP-16 and CDDP. The level increased in five patients during the course of chemotherapy and then decreased in relation to the degree of tumor reduction by chemotherapy. In the solid type of metastatic brain tumor, five of seven patients with multiple tumors showed high levels of MBP and these levels also returned to normal after treatment in four patients. As for the influence of irradiation, levels of MBP did not increase after irradiation except in three patients who developed radiation necrosis, local extensive edema or atrophic change. In other brain tumors, levels of MBP were high in a patient with a large meningioma with very extensive edema and during an unstable postoperative condition after total removal of a large craniopharyngioma.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers; Brain Diseases; Brain Neoplasms; Female; Humans; Male; Middle Aged; Myelin Basic Protein; Prognosis

To characterize the role of B lymphocytes in the pathogenesis of Multiple Sclerosis (MS), we have isolated mononuclear cells from cerebrospinal fluid (CSF) and stimulated them with a polyclonal B-cell mitogen (pokeweed mitogen). This study has been done with MS patients selected for the occurrence of an acute attack in the course of the disease and with patients hospitalized for other neurological diseases. Five of the 11 MS patients had B lymphocytes producing in vitro antibodies (Abs) directed against purified human myelin basic protein (hMBP), as revealed by Western blot analysis. None of the 20 patients with other neurological diseases showed such a reactivity. The produced Abs recognized only 1 or 2 hMBP peptides without dominance for a certain peptide. This result emphasizes the presence of B cells producing Abs against MBP in CSF of MS patients and shows the interest of studying mononuclear cells of CSF as a good marker of the pathogenesis.

Topics: Acute Disease; Adult; Aged; Autoantibodies; B-Lymphocytes; Biomarkers; Blotting, Western; Brain Diseases; Cells, Cultured; Cerebrospinal Fluid; Enzyme-Linked Immunosorbent Assay; Female; Humans; Lymphocyte Activation; Male; Middle Aged; Multiple Sclerosis; Myelin Basic Protein; Pokeweed Mitogens

We have evaluated a young woman with segmental spinal muscular atrophy, who has a deletion of a portion of the long arm of chromosome 18. She also has vitiligo and lichen sclerosis et atrophicus. She has neither the facial dysmorphism nor the mental deficit usually associated with the 18q- syndrome. Magnetic resonance imaging scan of her brain demonstrates high signal intensity consistent with abnormal myelination. Southern blot analysis of her DNA demonstrates that the deletion includes the gene for human myelin basic protein. Neither spinal muscular atrophy nor this patient's skin manifestations have been previously reported in association with 18q-.

Topics: Adult; Brain Diseases; Chromosome Deletion; Chromosomes, Human, Pair 18; DNA; Female; Humans; Karyotyping; Magnetic Resonance Imaging; Muscular Atrophy, Spinal; Myelin Basic Protein; Scleroderma, Localized; Vitiligo

Guinea pigs immunized with bovine spinal cord ventral horn homogenate develop muscle weakness with electromyographic and morphologic evidence of denervation. Pathological examination demonstrates a loss of motoneurons and scattered inflammatory foci primarily localized to the spinal cord. Immunohistochemical techniques document the presence of immunoglobulin G at the motor end plate and around the external membrane and within the cytoplasm of motoneurons. This syndrome of experimental autoimmune gray matter disease (EAGMD) differs from experimental autoimmune motor neuron disease induced by inoculation with purified motoneurons and also differs from experimental autoimmune encephalomyelitis. The existence of two different forms of immune-mediated motoneuron destruction suggests that a number of cytoplasmic and membrane antigens may give rise to an immunologically based attack on the motor system.

Topics: Animals; Antibodies; Autoimmune Diseases; Brain Diseases; Cattle; Complement C3; Electromyography; Guinea Pigs; Immunization; Immunoglobulin G; Immunohistochemistry; Male; Motor Neurons; Muscles; Myelin Basic Protein; Nervous System; Periaqueductal Gray; Spinal Cord

Rat lymphocyte lines were established, with specificity toward two synthetic peptides derived from the interphotoreceptor retinoid-binding protein (IRBP), which specifically localizes in the retina and pineal gland. One of the peptides, R4, is immunopathogenic, producing experimental autoimmune uveoretinitis (EAU) and pinealitis (EAP) in immunized rats, while the other peptide, R3, exhibits no detectable immunopathogenicity in rats. The cell lines carry surface markers specific for the helper/inducer subset of T-lymphocytes. When tested by the proliferation assay, the line cells demonstrated major histocompatibility-restricted vigorous responses against the immunizing (homologous) peptide, but failed to recognize the intact IRBP molecule. This finding is in line with other data indicating that peptides R3 and R4 are nonimmunodominant determinants of IRBP for the Lewis rat. Yet, the cell lines specific for R4 were highly immunopathogenic, producing EAU and EAP in naive rats at numbers as low as 0.25 x 10(6), with histopathological changes similar to those induced by active immunization with this peptide. The immunological capacity of the cell lines was further demonstrated by the finding that spleen cells from recipient rats of these lines responded well against the homologous peptides. The uniqueness of this system, in which lymphocytes specific toward a nondominant determinant are immunopathogenic, is underscored and the possible mechanisms of disease induction are discussed.

Topics: Animals; Autoimmune Diseases; Brain Diseases; Cell Line; Eye Proteins; Inflammation; Lymphocyte Activation; Male; Myelin Basic Protein; Pineal Gland; Rats; Rats, Inbred Lew; Retinitis; Retinol-Binding Proteins; T-Lymphocytes; Uveitis

A case of neurobrucellosis misdiagnosed at the onset as multiple sclerosis (MS) is presented. Magnetic resonance imaging showed multiple periventricular areas compatible with demyelinating lesions of possible vasculitic origin. Myelin basic protein was elevated in the CSF. The immunological CSF study was consistent with a chronic intrathecal inflammatory process. The modification of these parameters during specific treatment is also presented.

Topics: Brain Diseases; Brucellosis; Diagnosis, Differential; Female; Humans; Magnetic Resonance Imaging; Middle Aged; Multiple Sclerosis; Myelin Basic Protein

A case of widespread hemorrhagic and perivenous demyelinative leukoencephalomyelitis complicating a localized herpes simplex virus (HSV) brain stem infection is reported in a 28-year-old man. The presence of the virus is documented immunohistochemically and ultrastructurally. The spinal trigeminal tract at the level of the medulla oblongata contained viral antigen in the neurons, glia and in the vascular walls, including a few endothelial cells. The foci of demyelination showed deposits of gamma globulins and slight inflammatory infiltrations; the virus was absent from these lesions. It is postulated that HSV entered the central nervous system through the trigeminal nerve. Focal expression of the viral antigen on the endothelium in a sensitized host was the likely precipitating factor in the hyperacute autoimmune reaction, resulting in the widespread hemorrhagic and demyelinating lesions in the central nervous system.

Topics: Adult; Brain Diseases; Brain Stem; Encephalomyelitis, Autoimmune, Experimental; Glial Fibrillary Acidic Protein; Herpes Simplex; Humans; Immunoglobulin mu-Chains; Immunohistochemistry; Male; Myelin Basic Protein

Myelin basic protein (MBP) was serially measured in 177 CSF samples of 33 patients with leptomeningeal metastases and in 34 cancer controls. The mean level in cancer controls (free of neural involvement) was 5.7 +/- 0.33 ng/ml (normal less than 5 ng/ml) with abnormal elevation of MBP detected in 17%. The activity of the leptomeningeal disease was classified as either acute-progressive, stable or in remission on the basis of clinical and CSF cytological findings. CSF MBP levels were analysed in each stage. Abnormal elevation of MBP was detected in 74% of the 68 samples obtained in the acute-progressive stage (mean +/- SEM: 18.25 +/- 1.4 ng/ml, P less than 0.0001), in 24% of the 79 samples in the stable phase (mean: 7.99 +/- 0.8 ng/ml, NS) and in 20% of the 30 samples in remission (mean 5.7 +/- 0.3 ng/ml, NS). Similar changes in levels of CSF MBP were also observed in longitudinal studies of patients responding to treatment or relapsing to the acute stage. Eight patients developed treatment induced necrotizing leukoencephalopathy with typical CT-scan findings; elevated levels of CSF MBP were detected in 7 of them (mean: 21 +/- 3 ng/ml) when measured within 2 weeks of diagnosis but not when measured 2 months earlier. Our study suggests that in leptomeningeal metastases, CSF MBP levels are indicators of the disease activity, particularly if longitudinal determinations are used.

Topics: Adolescent; Adult; Aged; Brain Diseases; Breast Neoplasms; Cerebrospinal Fluid Proteins; Female; Humans; Leukemia, Lymphoid; Lymphoma, Non-Hodgkin; Male; Meningeal Neoplasms; Middle Aged; Myelin Basic Protein

It has been proposed that the biochemical lesion in subacute combined degeneration of the cord due to vitamin B12 deficiency, is impaired methylation of residue 107 (arginine) in myelin basic protein. We have examined myelin basic protein in brains of rats in which vitamin B12 was inactivated by exposure to nitrous oxide for up to 7 days. In addition brains of fruit bats in which vitamin B12 neuropathy had been produced by feeding washed, and hence vitamin B12-free fruit, were examined. There was no difference in the methylation of arginine 107 in myelin basic protein in these animals as compared to healthy control animals. Rats given an inhibitor of transmethylation reactions (cycloleucine) showed the expected fall in methylation of myelin basic protein.

Topics: Animals; Arginine; Brain Diseases; Chiroptera; Cycloleucine; Disease Models, Animal; Liver; Methylation; Myelin Basic Protein; Rats; Rats, Inbred Strains; Vitamin B 12; Vitamin B 12 Deficiency

Cerebrospinal fluid (CSF) from 221 patients with multiple sclerosis (MS) and 85 patients with other neurological disorders (OND) was examined using a competitive radioimmunoassay for myelin basic protein (MBP) immunoreactivity. MBP was found in 46 of 55 MS patients (84%) examined within six weeks of relapse but in only 11 of 85 patients (13%) with OND. There was a significant correlation between the concentration of MBP in the CSF and relapse severity in patients seen within four weeks of the onset of symptoms (p less than 0.01). Of 44 patients in remission, MBP was detected in 12, and these patients had a significantly higher tendency to subsequent relapse (p less than 0.05). In 72 patients with progressive disease the presence of MBP in the CSF reflected the confidence of clinical diagnosis. The results of this study suggest that measurement of MBP in the CSF gives an objective method of monitoring disease activity in patient with MS.

Topics: Acute Disease; Brain Diseases; Female; Humans; Male; Multiple Sclerosis; Myelin Basic Protein; Peripheral Nervous System Diseases; Recurrence; Remission, Spontaneous; Time Factors

A 30-year-old homosexual man presented with widespread Burkitt's lymphoma. On the basis of immunologic and viral studies, he was suspected of having the acquired immune deficiency syndrome. Following chemotherapy that included intrathecal cytosine arabinoside and methotrexate, brain stem edema, paraplegia, and an elevated cerebrospinal fluid level of myelin basic protein developed. Autopsy revealed vacuolar demyelination of spinal cord, brain stem, and cerebellum. The pathologic findings were similar to those reported to occur in myelopathy associated with intrathecal chemotherapy, but far more extensive. The contribution of the suspected acquired immune deficiency syndrome is unknown.

Topics: Acquired Immunodeficiency Syndrome; Adult; Antineoplastic Combined Chemotherapy Protocols; Brain Diseases; Brain Stem; Burkitt Lymphoma; Cerebellum; Demyelinating Diseases; Homosexuality; Humans; Injections, Spinal; Male; Myelin Basic Protein; Spinal Cord Diseases

Patients admitted to the neurosurgical wards for the management of nervous system tumours, subarachnoid and intracerebral haemorrhage, head injury, spinal and peripheral nerve lesions, and other miscellaneous neurosurgical conditions, were studied by assay of serum immunoreactivity for myelin basic protein. Of 171 patients, 70% proved to have elevated myelin basic protein activity. In cerebral cases the extent of brain damage assessed by clinical methods appeared to correlate with the appearance of elevated serum myelin basic protein. In spinal and peripheral nerve cases no similar elevation of myelin basic protein was observed.

Topics: Adolescent; Adult; Brain Diseases; Brain Neoplasms; Child; Child, Preschool; Female; Humans; Infant; Male; Middle Aged; Myelin Basic Protein; Nervous System Diseases; Peripheral Nervous System Diseases; Postoperative Complications; Prognosis; Radioimmunoassay; Spinal Cord Diseases

High-dose prostacyclin treatment during cardiopulmonary bypass reduces platelet activation and possibly postoperative blood loss. A side-effect is arterial hypotension. We studied the incidence of cerebral complications in 79 patients requiring coronary bypass. Only patients without known cerebrovascular disease were studied. Thirty-nine patients received prostacyclin 50 ng/kg/min during cardiopulmonary bypass and 40 patients served as controls. Mean arterial blood pressure in the group given prostacyclin was below 30 mm Hg during the first 30 minutes of bypass but remained above 60 mm Hg in the control group. Postoperative neurological examination revealed transient cerebral dysfunction in six control patients and two prostacyclin-treated patients. Investigation of cerebrospinal fluid showed signs of blood-brain barrier damage in 12 control and seven prostacyclin-treated patients. Cytologic changes in cerebrospinal fluid consistent with brain tissue damage occurred in two control patients but in no patient given prostacyclin. Myelin basic protein and adenylate kinase in cerebrospinal fluid were assayed as being markers of brain damage. Myelin basic protein was within the normal range in all patients. Adenylate kinase was moderately increased (greater than 0.035 U/L) in five of 15 control patients and six of 13 prostacyclin-treated patients. We conclude that treatment with prostacyclin 50 ng/kg/min during cardiopulmonary bypass does not increase the risk of postoperative cerebral damage.

Topics: Adenylate Kinase; Blood Pressure; Blood-Brain Barrier; Brain Diseases; Cardiopulmonary Bypass; Epoprostenol; Humans; Hypotension; Middle Aged; Myelin Basic Protein; Postoperative Complications

Eleven dogs were experimentally infected with canine distemper virus and studied for periods of up to 63 days post-inoculation. The responsiveness of lymphocytes in vitro toward phytohemagglutinin, myelin basic protein and galactocerebroside was tested at regular intervals during the course of infection by means of [3H]thymidine incorporation and flow cytometry. All dogs developed a marked decrease of lymphocyte responsiveness toward phytohemagglutinin. Four dogs recovered rapidly from the immunosuppression and did not develop demyelination or had only mild lesions, while two others failed to recover at all and developed severe non-inflammatory demyelinating lesions. The remaining dogs exhibited a slow or partial immune recovery and had various degrees of inflammatory demyelination. Lymphocytes from 2 dogs with demyelination and 2 dogs without myelin lesions responded to myelin antigens. The findings indicate that the degree of immunosuppression in canine distemper virus infection may determine the type of demyelination and autoimmune reactions that occur during the inflammatory stage of demyelination may be epiphenomena.

Topics: Animals; Antigens; Brain Diseases; Demyelinating Diseases; Distemper; Dogs; Galactosylceramides; Immunosuppression Therapy; Lectins; Lymphocyte Activation; Myelin Basic Protein; Phytohemagglutinins

Myelin basic protein (BP) is a specific constituent of the myelin sheath. This structural protein cannot be detected in the cerebrospinal fluid (CSF) unless myelin is acutely degraded. In order to detect active demyelinating diseases, BP was measured in CSF samples of radioimmunoassay. The assay is specific and sensitive to as little as 1.5 to 2.5 ng/ml BP. A moderate non-parallelism between the standard curve and various dilutions of CSF samples indicates that in CSF BP is present in an altered state. Over 1000 CSF samples have been measured in a double-blind study, in which 100 patients were selected and their clinical records evaluated. Twenty-eight patients without demyelinating disease had BP levels lower than 2.5 ng/ml. 72 patients had values higher than 2.5 ng/ml. Among them, the most frequent causes of demyelination were multiple sclerosis (19 cases), brain tumors (22 cases) and cerebral or spinal vascular accidents (12 cases). During a single acute demyelinating episode, BP levels revert to background levels within a few days. In contrast to immunological anomalies observed in the CSF, the presence of BP is concomitant with the breakdown of myelin. The size and location of the lesion influence the level of BP in the CSF. Thus, the assay is useful for the detection of active demyelination in the central nervous system and in following the course of the disease, although normal values do not rule out the presence of demyelinating lesions. For the time being, therefore, this assay should be restricted to specialized neurological centers and selected patients.

Topics: Adult; Brain Diseases; Brain Neoplasms; Central Nervous System Diseases; Child; Demyelinating Diseases; Female; Humans; Male; Meningoencephalitis; Multiple Sclerosis; Myelin Basic Protein; Radioimmunoassay

Topics: Adolescent; Adult; Brain; Brain Diseases; Child; Child, Preschool; Demyelinating Diseases; Humans; Leukemia, Lymphoid; Methotrexate; Myelin Basic Protein

Myelin basic protein in spinal fluid was measured with a radioimmunoassay method after surgery of brain tumors and posttraumatic brains in thirteen cases. Three cases were studied daily for up to three weeks. Immediately after the operation the values were high but then successively returned to normal. Repeated measurement of the myelin basic protein in spinal fluid seem to be useful for assessing the healing rate of brain tissue after surgery for brain tumors and after other brain damage.

Topics: Adult; Aged; Brain Diseases; Brain Neoplasms; Contusions; Ependymoma; Female; Glioma; Hematoma; Humans; Male; Meningioma; Middle Aged; Myelin Basic Protein; Postoperative Period; Skull Fractures

Topics: Adult; Brain Diseases; Child; Diagnosis, Differential; Electrophoresis; Erythrocytes; False Negative Reactions; False Positive Reactions; Humans; Immunization; Lymphocytes; Macrophages; Myelin Basic Protein; Neoplasms; Nerve Degeneration

Serum levels of myelin basic protein (M.B.P.), a nervous-system-specific protein, were measured in 157 patients after head injury and related both to the type of brain damage and to the clinical outcome assessed three months after injury. Mean concentrations of M.B.P. in patients with severe intracerebral damage, with or without associated extracerebral haematoma, were significantly raised at the time of admission and remained high for two weeks after injury. In patients with extracerebral haematoma not associated with severe intracerebral damage mean M.B.P. values rose four to six days after injury and were significantly raised only in patients with poor eventual outcome. Mean serum-M.B.P. concentrations in patients with a good outcome after injury were similar to those in controls. In patients with a poor outcome the mean M.B.P. levels between two and six days after injury were significantly higher than in those with a good outcome. The assay of serum-M.B.P. may be valuable in assessment of severity of brain damage in patients after head injury and in prediction of outcome.

Topics: Blood-Brain Barrier; Brain Diseases; Brain Injuries; Brain Neoplasms; Cerebrovascular Disorders; Craniocerebral Trauma; Hematoma; Humans; Myelin Basic Protein; Prognosis

Vaccinia virus infection was performed by scarification of the shaved skin (5 times 5 cm2) on the back of Pirbright guinea pigs. The macrophage migration inhibition test was performed with peritonealexudate cells 7, 11, 14 and 21 days after infection. Macrophage migration inhibition occurred after exposure of the cells to whole brain tissue antigen on the 7th, 11th, 14th day after infection (s. table 1). Lymphocyte transformation responses were examined by 14C-2-Thymidin uptake using blood cultures and basic encephalitogenic protein and whole brain tissue extract as antigens. A positive transformation response could be demonstrated from one to 8 weeks after infection (s. table 2). The specificity of the transformation response to brain antigen was established using control cultures stimulated with PHA or PPD. In no case stimulation occured with PPD. Stimulation with PHA was not altered. On the other hand the spontaneous lymphocyte transformation was enhanced at one week after infection and lymphocyte cultures exposed to heat inactivated vaccinia virus showed transformation from the 3th week after infection until the end of the observation period (i.e. 8 weeks) (s. table 2). The reason why cell mediated hypersensitivity to brain antigen is induced following vaccinia infection remains unknown. The most probable among several possible mechanisms seem a) the induction of virus-specific antigens on the surface of infected cells or b) the release of brain specific antigen through virus infection.

Topics: Administration, Topical; Animals; Antigens; Brain; Brain Diseases; Cell Migration Inhibition; Central Nervous System Diseases; Guinea Pigs; Immunity, Cellular; Immunization; Lectins; Lymphocyte Activation; Macrophage Migration-Inhibitory Factors; Macrophages; Myelin Basic Protein; Skin; Tuberculin; Vaccinia

Topics: Acute Disease; Antibodies; Brain Diseases; Chronic Disease; Encephalomyelitis; Female; Humans; Immunity, Cellular; Immunodiffusion; Iodine Radioisotopes; Lectins; Lymphocyte Activation; Male; Multiple Sclerosis; Myelin Basic Protein; Polyradiculopathy; Tritium