benzofurans and Spinal-Cord-Injuries

Prucalopride is a new prokinetic agent, recently available in Europe for the treatment of functional constipation in adults in whom treatment with laxatives failed to provide adequate relief. However, due to its intrinsic properties (highly selective agonist activity and high affinity for 5-HT4 receptors, neuroprotection), this drug has shown the potential to be used in other pathologic conditions, in and outside of the gastrointestinal tract. We performed a systematic review of the evidence supporting these possible alternative uses of prucalopride. Further studies in this area are, however, mandatory.

Topics: Analgesics, Opioid; Benzofurans; Colonic Diseases; Constipation; Humans; Ileus; Intestinal Pseudo-Obstruction; Multiple Sclerosis; Serotonin 5-HT4 Receptor Agonists; Spinal Cord Injuries

Chronic constipation (CC) often occurs after spinal cord injury (SCI). Prucalopride is a novel, highly selective, specific serotonin4 receptor agonist with enterokinetic properties. We evaluate the tolerability and pilot efficacy of prucalopride in the treatment of CC due to SCL.. Double-blind, placebo-controlled, pilot, phase 11, dose-escalation study. After 4 weeks' run in, patients received prucalopride 1 mg (n = 8) or placebo (n = 4); 11 new patients were randomized to prucalopride 2 mg (n = 8) or placebo (n = 3) once daily for 4 weeks. Patients recorded bowel function (diary) and assessed constipation severity and treatment efficacy (visual analogue scale (VAS) 0-100 mm). Colonic transit times were determined.. Compared with run in. mean changes in constipation severity (VAS) increased with placebo, but decreased with prucalopride 1 and 2 mg. The VAS score for treatment efficacy showed a clear dose response (medians 4, 52 and 73 for placebo, 1 and 2 mg, respectively). Diary data showed an improvement in average weekly frequency of all bowel movements over 4 weeks within the 2 mg group (median 0.6; 95% CI 0.2; 1.2). There was a significant reduction in median colonic transit time with 2 mg (n = 4; -38.5 h (95% CI -80; -5)). Four patients (2 mg) reported moderate/severe abdominal pain, and two of these discontinued treatment. There were no clinically relevant effects on any of the safety parameters.. This pilot study indicates that prucalopride can play an important role in the management of patients with CC due to SCI.

Topics: Adolescent; Adult; Benzofurans; Chronic Disease; Constipation; Defecation; Double-Blind Method; Female; Gastrointestinal Agents; Gastrointestinal Motility; Humans; Male; Middle Aged; Pilot Projects; Receptors, Serotonin; Receptors, Serotonin, 5-HT4; Serotonin Receptor Agonists; Spinal Cord Injuries

As a serious trauma of the neurological system, spinal cord injury (SCI) results in permanent disability, gives rise to immediate vascular damage and a wide range of matters that induce the breakage of blood spinal cord barrier (BSCB). SCI activates the expression of MMP-2/9, which are considered to accelerate the disruption of BSCB. Recent research shows that Dl-3-n-butylphthalide (NBP) exerted protective effects on blood spinal cord barrier in animals after SCI, but the underlying molecular mechanism of NBP on the BSCB undergoing SCI is unknown. Here, our research show that NBP inhibited the expression of MMP-2/9, then improved the permeability of BSCB following SCI. After the T9 level of spinal cord performed with a moderate injury, NBP was managed by intragastric administration and further performed once a day. NBP remarkably improved the permeability of BSCB and junction proteins degration, then promoted locomotion recovery. The protective effect of NBP on BSCB destruction is related to the regulation of MMP-2/9 induced by SCI. Moreover, NBP obviously inhibited the MMP-2/9 expression and junction proteins degradation in microvascular endothelial cells. In conclusion, our results indicate that MMP-2/9 are relevant to the breakdown of BSCB, NBP impairs BSCB destruction through inhibiting MMP-2/9 and promotes functional recovery subjected to SCI. NBP is likely to become a new nominee as a therapeutic to treat SCI via a transigent BSCB.

Topics: Animals; Benzofurans; Cell Hypoxia; Claudin-5; Female; Glucose; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Matrix Metalloproteinase Inhibitors; Mice; Neuroprotective Agents; Occludin; Oxygen; Rats, Sprague-Dawley; Recovery of Function; Spinal Cord; Spinal Cord Injuries; Tight Junction Proteins; Tight Junctions

An experimental animal study of treatment of spinal cord injury (SCI).. This report aims to evaluate the in vivo effects of butylphthalide NBP on SCI biology and to explore its potential mechanism.. SCI causes great damage to humans. The inflammatory and reconstructive processes after SCI is regulated by activation of astroglial and microglial cells. Activated microglia/macrophages can be divided into M2 (anti-inflammatory) and M1 (pro-inflammatory) phenotypes. Butylphthalide (3-n-butylphthalide or NBP) treatment can significantly alleviate ischemic brain damage, and further study has confirmed that central neuroprotective effects can be realized by converting M1 polarized microglia/macrophages to the M2 phenotype. Thus far, it remains unknown whether NBP can modulate the transition of macrophages/microglia between the M1 and M2 phenotypes.. We randomly divided male mice into three groups (sham group, SCI group, SCI+ NBP group). Molecular and histological tests were performed to detect the macrophage/microglia polarization as well as the potential mechanism of NBP in vivo and in vitro.. It was found that NBP treatment significantly attenuated the motor dysfunction and neuronal apoptosis induced by SCI. Treatment with NBP could also reduce pro-inflammatory cytokine release after SCI and could facilitate macrophage/microglia M2 polarization and inhibit M1 polarization after SCI. To verify the findings in animal experiments, we examined the effect of NBP on BV2 cell polarization, the results showed that NBP treatment could enhance M2 polarization and inhibit M1 polarization, and that M2 polarization occurred in a p38-dependent manner.. NBP plays an important role in the anti-inflammatory response in SCI via the facilitation of macrophage/microglia M2 polarization as well as the inhibition of macrophage/microglia M1 polarization. The M2 polarization of macrophages/microglia occurs via activation of p38 pathway.. 3.

Topics: Animals; Anti-Inflammatory Agents; Apoptosis; Benzofurans; Cell Polarity; Macrophages; Male; Mice; Mice, Inbred C57BL; Microglia; Neuroprotective Agents; p38 Mitogen-Activated Protein Kinases; Phosphorylation; Spinal Cord Injuries; Thoracic Vertebrae

Spinal cord injury (SCI) is a common type of injury, and about half of patients affected by SCI will suffer from neuropathic pain within a year after injury. However, the treatment effect of neuropathic pain is far from satisfactory. Our study attempted to reveal whether salvianolic acid B (SalB) could relieve the neuropathic pain caused by SCI in mice by inhibiting the Toll-like receptor 4 (TLR4)/Myeloid differentiation factor 88 (MyD88) pathway.. The mice were randomly divided into a sham group, model group, high-dose treatment group, and low-dose treatment group. The high- and low-dose groups received varying doses of SalB after modeling.. The increase of pain sensitivity was evaluated by detecting paw withdrawal mechanical threshold and withdrawal thermal latency. Messenger RNA and protein expression levels of TLR4 and myD88 were detected by using quantitative reverse-transcription polymerase chain reaction and western blot, respectively. Compared with the model group, there was a significant reduction in paw withdrawal mechanical threshold and withdrawal thermal latency after SalB treatment.. SalB reduced the release of tumor necrosis factor-α and substance P by inhibiting the TLR4/MyD88 pathway in the SCI mouse model. This not only resulted in lower pain, but also contributed to long-term relief of mechanical hyperalgesia.

Topics: Animals; Benzofurans; Hyperalgesia; Male; Mice; Myeloid Differentiation Factor 88; Neuralgia; Pain Threshold; Random Allocation; Spinal Cord Injuries; Toll-Like Receptor 4

Spinal cord injury (SCI) is a devastating disease inflicting lifetime disability to the victims. Military personnel are quite often victims of SCI for which no suitable therapeutic strategies have been developed so far. The main reason for SCI induced disability is loss of neural connections below and above the lesion site causing motor paralysis and somatosensory disturbances Loss of neuronal connections thwart spinal cord conduction resulting in motor function disability. To enhance spinal cord conduction grafting of peripheral nerves, implant of hydrogels filled with neuroprotective drugs is used but so far, no satisfactory results re achieved. In this regards implants of microelectrode for enhancing tissue connectivity is suggested that is still under experimental state. We have used titanium implant with or without TiO

Topics: Animals; Benzofurans; Capillary Permeability; Drug Delivery Systems; Drug Implants; Edema; Evoked Potentials; Locomotion; Male; Nanostructures; Nanowires; Neuroprotective Agents; Rats; Spinal Cord Injuries; Titanium

In this study, we examined the neuroprotective effects and anti-inflammatory properties of Dl-3-n-butylphthalide (NBP) in Sprague-Dawley (SD) rats following traumatic spinal cord injury (SCI) as well as microglia activation and inflammatory response both in vivo and in vitro. Our results showed that NBP improved the locomotor recovery of SD rats after SCI an significantly diminished the lesion cavity area of the spinal cord, apoptotic activity in neurons, and the number of TUNEL-positive cells at 7 days post-injury. NBP inhibited activation of microglia, diminished the release of inflammatory mediators, and reduced the upregulation of microglial TLR4/NF-κB expression at 1 day post-injury. In a co-culture system with BV-2 cells and PC12 cells, NBP significantly reduced the cytotoxicity of BV-2 cells following lipopolysaccharide (LPS) stimulation. In addition, NBP reduced the activation of BV-2 cells, diminished the release of inflammatory mediators, and inhibited microglial TLR4/NF-κB expression in BV-2 cells. Our findings demonstrate that NBP may have neuroprotective and anti-inflammatory properties in the treatment of SCI by inhibiting the activation of microglia via TLR4/NF-κB signalling.

Topics: Animals; Anti-Inflammatory Agents; Benzofurans; Cell Line; Coculture Techniques; Female; Gene Expression Regulation; Lipopolysaccharides; Microglia; Neuroprotective Agents; NF-kappa B; PC12 Cells; Rats; Rats, Sprague-Dawley; Signal Transduction; Spinal Cord; Spinal Cord Injuries; Toll-Like Receptor 4

After spinal cord injury (SCI), the destruction of blood-spinal cord barrier (BSCB) is shown to accelerate gathering of noxious blood-derived components in the nervous system, leading to secondary neurodegenerative damages. SCI activates endoplasmic reticulum stress (ER stress), which is considered to evoke secondary damages of neurons and glia. Recent evidence indicates that Dl-3-n-butylphthalide (NBP) has the neuroprotective effect in ischaemic brain injury, but whether it has protective effects on SCI or not is largely unclear. Here, we show that NBP prevented BSCB disruption after SCI via inhibition of ER stress. Following a moderate contusion injury of the T9 level of spinal cord, NBP was administered by oral gavage and further treated once a day. NBP significantly attenuated BSCB permeability and breakdown of adherens junction (AJ) and tight junction (TJ) proteins, then improved locomotion recovery following SCI. The protective role of NBP on BSCB disruption is associated with the restrain of ER stress caused by SCI. Furthermore, NBP considerably constrained the expression of ER stress-associated proteins and degradation of TJ and AJ in human brain microvascular endothelial cells (HBMECs) treated with TG. In conclusion, our results indicate that ER stress is associated with the disruption of BSCB integrity after injury, NBP attenuates BSCB disruption via inhibiting ER stress and improve functional recovery following SCI.

Topics: Adherens Junctions; Animals; Benzofurans; Blood-Brain Barrier; Cells, Cultured; Endoplasmic Reticulum Stress; Female; Humans; Locomotion; Rats; Rats, Sprague-Dawley; Recovery of Function; Spinal Cord; Spinal Cord Injuries; Tight Junctions

Extracellular matrix molecule chondroitin sulfate proteoglycans (CSPGs) are highly upregulated in scar tissues and form a potent chemical barrier for CNS axon regeneration. Recent studies support that the receptor protein tyrosine phosphatase σ (PTPσ) and its subfamily member leukocyte common antigen related phosphatase (LAR) act as transmembrane receptors to mediate CSPG inhibition. PTPσ deficiency increased regrowth of ascending axons into scar tissues and descending corticospinal tract (CST) axons into the caudal spinal cord after spinal cord injury (SCI). Pharmacological LAR inhibition enhanced serotonergic axon growth in SCI mice. However, transgenic LAR deletion on axon growth in vivo and the role of LAR in regulating regrowth of other fiber tracts have not been studied. Here, we studied the role of LAR in restricting regrowth of injured descending CNS axons in deficient mice. LAR deletion increased regrowth of serotonergic axons into scar tissues and caudal spinal cord after dorsal over-hemitransection. LAR deletion also stimulated regrowth of CST fibers into the caudal spinal cord. LAR protein was upregulated days to weeks after injury and co-localized to serotonergic and CST axons. Moreover, LAR deletion improved functional recovery by increasing BMS locomotor scores and stride length and reducing grid walk errors. This is the first transgenic study that demonstrates the crucial role of LAR in restricting regrowth of injured CNS axons.

Topics: Animals; Benzofurans; Biotin; Brain; Dextrans; Disease Models, Animal; Female; Gene Expression Regulation; Mice; Mice, Knockout; Motor Activity; Mutation; Nerve Regeneration; Pyramidal Tracts; Quinolines; Receptor-Like Protein Tyrosine Phosphatases, Class 2; Recovery of Function; Serotonin; Spinal Cord Injuries; Time Factors

Salvianolic acid B (SalB), the main bioactive compound isolated from the traditional Chinese medicinal herb broad Radix Salviae Miltiorrhizae exerts a spectrum of pharmacologic activities. We investigated the effects of SalB treatment in a rat model of spinal cord ischemia and reperfusion (I/R) injury and the underlying mechanism.. SalB was administered at 1, 10, or 50 mg/kg after spinal cord ischemia. The potential protective effects on spinal cord injury were determined by spinal cord edema, infarct volume, and motor function assessment of the hind limbs.. SalB treatment significantly decreased spinal cord edema and infarct volume and preserved motor function of the hind limbs in a dose-dependent manner. SalB administration ameliorated the generation of oxidative products and preserved antioxidant defense activities in the injured spinal cord at both 4 and 24 h after I/R injury. Moreover, SalB prolonged the I/R injury-induced activation of extracellular signal-regulated kinase (ERK), and blocking ERK activation with PD98059 partially prevented the neuroprotective effects of SalB.. These findings demonstrate the neuroprotective effects of SalB in a spinal cord I/R injury model and suggest that SalB-induced neuroprotection was mediated by ERK activation.

Topics: Animals; Antioxidants; Benzofurans; Drug Evaluation, Preclinical; Drugs, Chinese Herbal; Hemodynamics; Locomotion; Male; MAP Kinase Signaling System; Oxidative Stress; Phytotherapy; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Spinal Cord Injuries

To evaluate the role of M2 and M3 muscarinic acetylcholine receptor (mAChR) subtypes in the activation of bladder afferent pathways in rats with chronic spinal cord injury (SCI).. Adult female Sprague-Dawley rats were spinalized at the T9 level. Continuous cystometry was performed under awake conditions 2 or 4 weeks after SCI. The effects of intravesical administration of an mAChR agonist (oxotremorine-methiodide), a nonselective antagonist (atropine), an M2-selective antagonist (methoctramine), and an M3-selective antagonist (darifenacin) were examined. After cystometry, the bladder was removed and separated into the mucosa and detrusor, and the M2 and M3 mAChR mRNA expression in the mucosa was determined using real-time quantitative polymerase chain reaction.. At 2 and 4 weeks after SCI, intravesical administration of a nonselective mAChR agonist (25 μM oxotremorine-methiodide) increased the area under the curve of nonvoiding contractions, although the intercontraction interval of voiding contractions and maximal voiding pressure did not change. This effect was blocked by atropine and methoctramine (10 μM) but not by darifenacin (50 μM). However, mAChR antagonists alone (10-50 μM) had no effect on cystometric parameters. M2 mAChR mRNA expression was increased in the mucosa of SCI rats compared with that in normal rats.. Our results suggest that the M2 mAChR subtype plays an important role in bladder afferent activation that enhances detrusor overactivity in SCI rats. However, because mAChR antagonists alone did not affect any cystometric parameters, the muscarinic mechanism controlling bladder afferent activity might not be involved in the emergence of detrusor overactivity in SCI.

Topics: Afferent Pathways; Animals; Atropine; Benzofurans; Diamines; Female; Mucous Membrane; Muscarinic Agonists; Muscarinic Antagonists; Muscle Contraction; Muscle, Smooth; Oxotremorine; Parasympatholytics; Pressure; Pyrrolidines; Rats; Rats, Sprague-Dawley; Receptor, Muscarinic M2; Receptor, Muscarinic M3; RNA, Messenger; Spinal Cord Injuries; Thoracic Vertebrae; Urinary Bladder; Urinary Bladder, Overactive

Our previous studies showed that ligands to type 2 imidazoline receptors (I₂R), including 2-(2-Benzofuranyl)-2-imidazoline (2-BFI) and Idazoxan, were effective in reducing spinal cord inflammation caused by experimental autoimmune encephalomyelitis (EAE). In the present study, we determined the effective therapeutic time window of 2-BFI and found that administration of 2-BFI in mice before the appearance of ascending flaccid paralysis (1-10 days post immunization), but not during the period when neurological deficits occurred (11-20 days post immunization), significantly ameliorated EAE-induced neurobehavioral deficits, reduced the infiltration of inflammatory cells into the spinal cord, and reduced the level of demyelination. More interestingly, giving 2-BFI during 1-10 days post immunization selectively suppressed IL-17 levels in the peripheral blood, which strongly suggests that IL-17 may be a good early marker to indicate EAE progression and that 2-BFI may target CD4⁺ T lymphocytes, especially Th17 cells to reduce IL-17 expression. Collectively, these studies led us to envisage that 2-BFI can be a useful drug to treat multiple sclerosis (MS) when used in combination with an early indicator of MS progression, such as IL-17.

Topics: Analysis of Variance; Animals; Benzofurans; Calcium-Binding Proteins; Cytokines; Disease Models, Animal; Encephalomyelitis, Autoimmune, Experimental; Enzyme-Linked Immunosorbent Assay; Freund's Adjuvant; Imidazoles; Indoles; Mice; Mice, Inbred C57BL; Microfilament Proteins; Myelin Sheath; Myelin-Oligodendrocyte Glycoprotein; Nervous System Diseases; Peptide Fragments; Spinal Cord Injuries; Time Factors

The lack of disease-modifying pharmacological agents for effective treatment of multiple sclerosis (MS) still represents a large and urgent unmet medical need. Our previous studies showed that ligands to type 2 imidazoline receptors (I(2)R) were effective in protecting spinal cord injury caused by experimental autoimmune encephalomyelitis (EAE), a mouse model of MS. In this study, we further examined the protective property of a very selective ligand of I(2)R, 2-(2-benzofuranyl) 2-imidazoline (2-BFI) against EAE. Importantly, a mechanism of 2-BFI-mediated protection was investigated which possibly involves an I(2)R binding protein, brain-creatine kinase (B-CK), as well as CaATPase and calpain. The enzymatic activity of B-CK and CaATPase was significantly reduced in EAE injured spinal cord. Reduction of B-CK activity in EAE spinal cord may lead to energy reduction and dysfunction in cellular calcium homeostasis. Increased intracellular calcium evokes elevation of calpain activity occurring in EAE spinal cord which causes further tissue damage. Indeed, EAE injured spinal cord showed significant reduction in CaATPase and increase calpain activities. Remarkably, spinal cord tissue from mice treated daily with 2-BFI during the progression of EAE significantly restored B-CK and CaATPase enzymatic activities and showed no induction in calpain activity. Moreover, EAE spinal cord from 2-BFI treated mice also demonstrated better preservation of myelin; reduced axonal injury, as evidenced by the lower level of β-APP expression, and above all, highly improved neurobehavioral scores (p<0.01; n=10). These findings suggest that 2-BFI can be further developed as a therapeutic drug for MS treatment.

Topics: Animals; Axons; Benzofurans; Calcium-Transporting ATPases; Calpain; Creatine Kinase, BB Form; Encephalomyelitis, Autoimmune, Experimental; Female; Imidazoles; Mice; Mice, Inbred C57BL; Multiple Sclerosis; Spinal Cord Injuries

Stem cells hold great promise for brain and spinal cord injuries (SCI), but cell survival following transplantation to adult central nervous system has been poor. Salvianolic acid B (Sal B) has been shown to improve functional recovery in brain-injured rats. The present study was designed to determine whether Sal B could improve transplanted mesenchymal stem cell (MSC) survival in SCI rats.. SCI rats were treated with Sal B. The Basso-Beatie-Bresnahan (BBB) scale was used to test the functional recovery. Sal B was used to protect MSC from being damaged by TNF-alpha in vitro. Bromodeoxyuridine-labeled MSC were transplanted into SCI rats with Sal B intraperitoneal injection, simultaneously. MSC were examined, and the functional recovery of the SCI rats was tested.. Sal B treatment significantly reduced the lesion area from 0.26+/-0.05 mm2 to 0.15+/-0.03 mm2 (P<0.01) and remarkably raised the BBB scores on d 28, post-injury, from 7.3+/-0.9 to 10.5+/-1.3 (P<0.05), compared with the phosphate-buffered saline (PBS) control group. MSC were protected from the damage of TNF-alpha by Sal B. The number of surviving MSC in the MSC plus Sal B groups were 1143.3+/-195.6 and 764.0+/-81.3 on d 7 and 28, post-transplantation, more than those in the MSC group, which was 569.3+/-72.3 and 237.0+/-61.3, respectively (P<0.05). Rats with MSC transplanted and Sal B injected obtained higher BBB scores than those with MSC transplanted alone (P<0.05) and PBS (P<0.01).. Sal B provides neuroprotection to SCI and promotes the survival of MSC in vitro and after cell transplantation to the injured spinal cord in vivo.

Topics: Animals; Antioxidants; Behavior, Animal; Benzofurans; Cell Survival; Male; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Rats; Rats, Sprague-Dawley; Spinal Cord Injuries; Tumor Necrosis Factor-alpha

A partial recovery of locomotor functions has been shown in spinal cord-transected (Tx) cats after regular treadmill training and repeated administration of clonidine, an alpha(2)-adrenoreceptor agonist. However, clonidine has generally failed to show prolocomotor effects in other models (e.g., rat or mudpuppy in vitro-isolated spinal cord preparations). The reasons for this discrepancy remain unclear, but they may suggest condition- or species-specific effects induced by clonidine. This study is aimed at examining both the acute (at 6 or 41 days post-Tx) and chronic effects of repeated (once a week for one month) clonidine administration (0.25-5.0 mg/kg i.p.) on hindlimb movement generation in Tx mice (thoracic segment9/10). Locomotor-like (LM) and nonlocomotor movements (NLM) were assessed both in open-field and treadmill conditions. The results show that clonidine consistently failed, in both conditions, to induce LM and NLM at all time points even though control experiments revealed hindlimb movements steadily induced by 8-hydroxy-2-(di-N-propylamino)-tetralin (8-OH-DPAT), a serotonin receptor agonist. In turn, clonidine acutely suppressed (I(1)-imidazoline receptor-mediated) the frequency of spontaneously occurring LM and NLM but apparently increased spinal excitability over time, because the frequency of spontaneous LM and NLM was significantly greater in clonidine-treated (before an injection) than vehicle-treated animals after repeated administration for a few weeks. The results clearly show that clonidine can not acutely induce hindlimb movements in untrained and otherwise nonstimulated (e.g., no tail or perineal pinching) Tx mice, although repeated administration may progressively facilitate the expression of spontaneous hindlimb movements.

Topics: Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-2 Receptor Antagonists; Adrenergic alpha-Agonists; Adrenergic alpha-Antagonists; Animals; Benzofurans; Clonidine; Hindlimb; Imidazoles; Imidazoline Receptors; Male; Mice; Mice, Inbred Strains; Movement; Receptors, Adrenergic, alpha-2; Spinal Cord; Spinal Cord Injuries; Yohimbine

Micturition was evoked in conscious cats by infusing saline into the bladder at a physiological rate. Drugs were administered intrathecally. Micturition volume threshold was increased by 5-hydroxytryptamine (5-HT, serotonin) and decreased by zatosetron, a 5-HT3 receptor antagonist, in spinally intact cats. Thus 5-HT3 receptors inhibit micturition. After complete spinal transection, serotonin reduced volume threshold in 3 of 4 cats, indicating an alteration in serotonergic control. However, 2-methyl-5-HT, a 5-HT3 receptor agonist, increased volume threshold. Thus 5-HT3 receptor-mediated inhibition of bladder function remains after spinal transection. We conclude that some, but not all, serotonergic modulation of bladder function is altered after spinal transection.

Topics: Animals; Benzofurans; Bridged Bicyclo Compounds, Heterocyclic; Cats; Dose-Response Relationship, Drug; Male; Serotonin; Spinal Cord; Spinal Cord Injuries; Time Factors; Urinary Bladder; Urination