g(m1)-ganglioside and Spinal-Cord-Injuries

Topics: G(M1) Ganglioside; Humans; Methylprednisolone; Neuroprotective Agents; Spinal Cord Injuries

Spinal cord injury (SCI) results in loss of feeling and movement. The consequences can be devastating for the patient and his or her carers. Global estimates of the number of new cases annually range from 15 to 40 per million. Leading causes of acute SCI are road traffic injury, violence, and injuries sustained in sports and other recreational activities. Care for people with SCI has improved, leading to an increase in survival rates. Attempts to improve patients' feeling and movement have involved the use of a wide range of treatments. Gangliosides are compounds that occur naturally in cell membranes. Laboratory studies have suggested they may have protective effects on nerves and even help them to re-grow. Clinical trials have taken place using gangliosides (usually GM1 ganglioside) for a number of neurological conditions.. To quantify the evidence for the effectiveness and safety of gangliosides when used to treat acute SCI.. We searched the following databases to identify trials for inclusion: CENTRAL, MEDLINE, EMBASE, and the National Research Register. We also searched web-based trials registers, such as Current Controlled Trials. We approached the manufacturers of the most widely used ganglioside and researchers in this field to try to locate any unpublished data.. Randomised controlled trials of any ganglioside versus controls, in patients with SCI. Outcome measures specified were: mortality, recovery of motor function, improvement in sensory measures, measures of functional activity, infections and any other adverse events.. Data were extracted from published studies and authors were contacted for further information. All data found was dichotomous and odds ratios (with 95% CIs) were calculated. A fixed-effects model was assumed.. Two studies met the inclusion criteria. There were no deaths in one (n=37). In the other (n=760), there were slightly more deaths in the treatment group than in the control group; odds ratio 1.07 (0.57, 2.00 95%CI) - a result that can be explained by the play of chance. Methodological weaknesses regarding the collection and presentation of data from the two studies made it impossible to reach any conclusions regarding the effect of gangliosides on the other specified outcomes.. The evidence available does not support the use of ganglioside treatment to reduce the death rate in SCI patients. No evidence has yet emerged that ganglioside treatment improves recovery or quality of life in survivors.

Topics: Acute Disease; G(M1) Ganglioside; Gangliosides; Humans; Randomized Controlled Trials as Topic; Spinal Cord Injuries

To review the major pharmacological trials in acute spinal cord injury (SCI) that have been conducted over the past 25 years.. Review article.. The publication of the first National Acute Spinal Cord Injury (NASCIS) trial in 1984 ushered in the era of pharmacological trials of therapies intended to improve neurologic outcome in acute SCI. Subsequent trials of methylprednisolone sodium succinate (MPSS) and GM-1 have added to the evidence basis that informs the current management practices for acute SCI.. The last 50 years have seen a conceptual shift from the pessimism of the past to a cautious optimism that the meager prognosis for neurologic recovery in acute SCI will yield to the progress of medical science. Major advances in the understanding of primary and secondary injury mechanisms have led to the preclinical study of many promising pharmacological therapies, all with the goal of improving neurologic outcome. A few of these drugs have stood the test of animal model experiments and have made it to the forum of human clinical trials. The NASCIS trials of methylprednisolone have been acknowledged widely as the first human studies to claim improved neurologic outcome. Although the results of these trials remain controversial, the MPSS therapy that they reported has been adopted widely by clinicians around the world as the best currently available, even if not a consensus "standard of care." Clearly, the challenge for medical science remains. The search for effective treatment has only begun.

Topics: Acute Disease; Clinical Trials as Topic; G(M1) Ganglioside; Humans; Methylprednisolone Hemisuccinate; Neuroprotective Agents; Spinal Cord Injuries

There is insufficient evidence to support treatment standards.. There is insufficient evidence to support treatment guidelines.. Treatment with methylprednisolone for either 24 or 48 hours is recommended as an option in the treatment of patients with acute spinal cord injuries that should be undertaken only with the knowledge that the evidence suggesting harmful side effects is more consistent than any suggestion of clinical benefit. GM-1 GANGLIOSIDE:. Treatment of patients with acute spinal cord injuries with GM-1 ganglioside is recommended as an option without demonstrated clinical benefit.

Topics: Acute Disease; Cervical Vertebrae; Critical Pathways; Evidence-Based Medicine; G(M1) Ganglioside; Humans; Methylprednisolone; Practice Guidelines as Topic; Spinal Cord Injuries

There are no drugs specifically approved for spinal cord injury that directly address the underlying damage to neural tissue. Immediate treatment with methylprednisolone sodium succinate has been shown to improve outcome from injury in a series of preclinical and clinical studies, and it is now widely used, though the benefits appear to be modest. A variety of other approaches to protecting the injured spinal cord from secondary pathological processes have been examined experimentally, including antioxidants, membrane stabilizers, glutamate antagonists, anti-inflammatories, caspase inhibitors, calpain inhibitors and other compounds of uncertain mechanism. All of these approaches have been supported by positive animal studies but their efficacy relative to the widely used methylprednisolone has not been established.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Enzyme Inhibitors; G(M1) Ganglioside; Humans; Neuroprotective Agents; Sodium Channel Blockers; Spinal Cord Injuries

The search for a pharmacologic treatment of acute spinal cord injury (SCI) dates back to the 1960s. It was not until 1990 that the pharmacologic agent methylprednisolone demonstrated improved outcomes in humans. Methylprednisolone has shown superiority to placebo in humans in two large, multicenter trials, and is the standard of care thus far. Other potentially useful agents include tirilazad, ganglioside (GM-1), and naloxone. Additional studies are needed for these agents to determine the optimal dose and timing of administration.

Topics: Acute Disease; Antioxidants; G(M1) Ganglioside; Humans; Methylprednisolone; Naloxone; Narcotic Antagonists; Neuroprotective Agents; Pregnatrienes; Spinal Cord Injuries

The search for a pharmacologic treatment of acute spinal cord injury (SCI) dates back to the 1960s. It was not until 1990 that the pharmacologic agent methylprednisolone demonstrated improved outcomes in humans. Methylprednisolone has shown superiority to placebo in humans in two large, multicenter trials, and is the standard of care thus far. Other potentially useful agents include tirilazad, ganglioside (GM-1), and naloxone. Additional studies are needed for these agents to determine the optimal dose and timing of administration.

Topics: Acute Disease; Anti-Inflammatory Agents; Drug Interactions; G(M1) Ganglioside; Humans; Methylprednisolone; Naloxone; Narcotic Antagonists; Neuroprotective Agents; Pregnatrienes; Research Design; Spinal Cord Injuries; Treatment Outcome

Only limited therapeutic measures are currently available for the treatment of spinal cord injury. This review describes the pathologic mechanisms of trauma-induced spinal cord injury in rats, which will contribute to new understanding of the pathologic process leading to spinal cord injury and to further development of new therapeutic strategies. Spinal cord injury induced by trauma is a consequence of an initial physical insult and a subsequent progressive injury process that involves various pathochemical events leading to tissue destruction; the latter process should therefore be a target of pharmacological treatment. Recently, activated neutrophils have been shown to be implicated in the latter process of the spinal cord injury in rats. Activated neutrophils damage the endothelial cells by releasing inflammatory mediators such as neutrophil elastase and oxygen free radicals. Adhesion of activated neutrophils to the endothelial cell could also play a role in endothelial cell injury. This endothelial cell injury could in turn induce microcirculatory disturbances leading to spinal cord ischemia. We have found that some therapeutic agents that inhibit neutrophil activation alleviate the motor disturbances observed in the rat model of spinal cord injury. Methylprednisolone (MPS) and GM1 ganglioside, which are the only two pharmacological agents currently clinically available for treatment of acute spinal cord injury, do not inhibit neutrophil activation in this rat model. Taken together, these observations raise a possibility that other pharmacological agents that inhibit neutrophil activation used in conjunction with MPS or GM1 ganglioside may have a synergistic effect in the treatment of traumatic spinal cord injury in humans.

Topics: Animals; Disease Models, Animal; G(M1) Ganglioside; Glucocorticoids; Leukocytes; Methylprednisolone; Rats; Spinal Cord Injuries

We review the evidence supporting the role of glucocorticosteroids, trilazad, and GM1 ganglioside in spinal cord injury and provide our critique of the published studies, along with our recommendations for pharmacologic therapy for this complex and difficult problem.

Topics: 4-Aminopyridine; Animals; Calcium Channel Blockers; Clinical Trials as Topic; Double-Blind Method; Drug Evaluation, Preclinical; Free Radical Scavengers; G(M1) Ganglioside; Glucocorticoids; Humans; Methylprednisolone; Multicenter Studies as Topic; Naloxone; Neuroprotective Agents; Pregnatrienes; Randomized Controlled Trials as Topic; Spinal Cord Injuries; Treatment Outcome

Topics: Adolescent; Adult; Cervical Vertebrae; Diagnostic Imaging; Emergency Medical Services; Female; G(M1) Ganglioside; Humans; Hypothermia, Induced; Lipid Peroxides; Male; Methylprednisolone; Middle Aged; Naloxone; Physical Examination; Pregnatrienes; Resuscitation; Spinal Cord Injuries; Thyrotropin-Releasing Hormone

Gangliosides are glycosphingolipids localized to the outer leaflet of the plasma membrane of vertebrate cells. The highest ganglioside concentration of any organ is found in the mammalian brain, where the gangliosides are enriched in the neuronal membrane, particularly in the synapses. There are four major brain gangliosides with the same neutral tetrasaccharide core to which one to three sialic acids are linked--the simplest being the GM1-ganglioside. These gangliosides have been shown to have neuritogenic and neuronotrophic activity and to facilitate repair of neuronal tissue after mechanical, biochemical or toxic injuries. Mixtures of native bovine brain gangliosides were adopted for pharmacological use in the treatment of peripheral nerve damage, and GM1-ganglioside has been applied for the treatment of CNS injuries and diseases. Beneficial effects of GM1 have been documented in the treatment of stroke and spinal cord injuries, particularly when the treatment has been initiated within a few hours of the acute event. Continuous intraventricular infusion of GM1 has recently been shown to have a significant beneficial effect in Alzheimer disease of early onset (AD Type I).

Topics: Alzheimer Disease; Animals; Carbohydrate Sequence; Cerebrovascular Disorders; G(M1) Ganglioside; Humans; Molecular Sequence Data; Spinal Cord Injuries

Two recent prospective, randomized, placebo-controlled, double-blinded clinical drug studies in acute spinal cord injury have reported enhancement of neurologic recovery of motor function. The drugs investigated in these studies were methylprednisolone and GM-1 ganglioside. Before these studies, the treatment of patients with spinal cord injuries had been restricted to prevention of further injury to the spinal cord, limiting secondary damage following the initial injury, increasing the patient's ability to function through intensive rehabilitation, and facilitating any spontaneous recovery of neurologic function. Methylprednisolone is a steroid administered at very high levels, and GM-1 is a complex acidic glycolipid found at high levels in cell membranes in the mammalian central nervous system with known neuroprotective and neurofunctional restoration potential. This article summarizes the previously reported Maryland GM-1 clinical trial and presents the clinical and statistical design of a larger clinical trial being conducted with the purpose of verifying a beneficial GM-1 drug effect when administered with methylprednisolone in acute spinal cord injury.

Topics: Critical Care; Double-Blind Method; G(M1) Ganglioside; Humans; Methylprednisolone; Prospective Studies; Spinal Cord Injuries; Trauma Centers

Continued investigation of the pathophysiology of primary and secondary neuronal injury following acute spinal cord injury (SCI) has led to positive results in two medical treatment protocols: methylprednisolone and GM1 ganglioside. The advent of improved high resolution radiologic studies has allowed a new dimension in the understanding of the physical and pathomechanical aspects of acute SCI. Advances in rehabilitation continue, allowing improved prognosis and long-term function. Prevention is clearly the best and most effective treatment of all.

Topics: G(M1) Ganglioside; Humans; Intervertebral Disc Displacement; Magnetic Resonance Imaging; Methylprednisolone; Neurologic Examination; Spinal Cord; Spinal Cord Injuries

Gangliosides play important roles in the physiologic operations of the nervous system, in particular that of the brain. Changes in ganglioside composition occur in the mammalian brain not only during development, but also in aging and in several neuropathologic situations. Gangliosides may modulate the ability of the brain to modify its response to signals from the surrounding environment. For example, cultured neurons respond to exogenous gangliosides with changes characteristic of differentiation; these sialoglycosphingolipids also amplify the response of neurons to neurotrophic factors. Additional in vitro studies have shown that monosialogangliosides like GM1 protect against excitatory amino acid-related neurotoxicity by limiting the downstream consequences of receptor overstimulation. Systemic administration of GM1 is efficacious in reducing acute nerve cell damage and in facilitating medium- and long-term functional recovery following various types of injury to the adult mammalian central nervous system. The GM1 protective effects in the acute injury phase likely result, at least in part, from attenuation of excitotoxicity, while long-term functional recovery may reflect GM1 potentiation of neurotrophic factors. The potential therapeutic efficacy of GM1 is encouraged by recent positive clinical findings in acute human stroke, subarachnoid hemorrhage, and spinal cord injury.

Topics: Animals; Brain Injuries; Cell Differentiation; Central Nervous System; G(M1) Ganglioside; Gangliosides; Humans; Neurons; Neurotoxins; Spinal Cord Injuries

To evaluate the functional and immunohistochemical effects of ganglioside GM1 and erythropoietin following experimental spinal cord injury.. Thirty-two male BALB/c mice were subjected to experimental spinal cord injury using the NYU Impactor device and were randomly divided into the following groups: GM1 group, receiving standard ganglioside GM1 (30 mg/kg); erythropoietin group, receiving erythropoietin (1000 IU/kg); combination group, receiving both drugs; and control group, receiving saline (0.9%). Animals were evaluated according to the Basso Mouse Scale (BMS) and Hindlimb Mouse Function Score (MFS). After euthanasia, the immunohistochemistry of the medullary tissue of mice was analyzed. All animals received intraperitoneal treatment.. The GM1 group had higher BMS and MFS scores at the end of the experiment when compared to all other groups. The combination group had higher BMS and MFS scores than the erythropoietin and control groups. The erythropoietin group had higher BMS and MFS scores than the control group. Immunohistochemical tissue analysis showed a significant difference among groups. There was a significant increase in myelinated axons and in the myelinated axon length in the erythropoietin group when compared to the other intervention groups (p < 0.01).. Erythropoietin and GM1 have therapeutic effects on axonal regeneration in mice subjected to experimental spinal cord injury, and administration of GM1 alone had the highest scores on the BMS and MFS scales.

Topics: Animals; Disease Models, Animal; Epoetin Alfa; Erythropoietin; G(M1) Ganglioside; Injections, Intraperitoneal; Male; Mice; Spinal Cord; Spinal Cord Injuries

Topics: Adult; Aged; Biomarkers; Blood Cell Count; Disease Progression; Female; G(M1) Ganglioside; Humans; Longitudinal Studies; Male; Middle Aged; Recovery of Function; Spinal Cord Injuries; Time Factors; Young Adult

Randomized, double-blind, sequential, multicenter clinical trial of two doses of Sygen versus placebo.. To determine efficacy and safety of Sygen in acute spinal cord injury.. An earlier, single-center trial in 28 patients showed an improvement (50.0% vs. 7.1%, P = 0.034) in marked recovery with Sygen.. Standard clinical trial techniques.. The prospectively planned analysis at the prespecified endpoint time for all patients was negative. There was a significant effect in all patients in the primary outcome variable (the percentage of marked recovery) at week 8, the end of the dosing period. There was a significant effect in all patients in the time at which marked recovery is first achieved. Restricted to severity Group B, which has small sample size, the primary efficacy analysis showed a trend but did not reach significance. There is a large, consistent and, at some time points, significant effect in the primary outcome variable in the nonoperated patients through week 26. The American Spinal Injury Association motor, light touch, and pinprick scores showed a consistent trend in favor of Sygen, as also did bowel function, bladder function, sacral sensation, and anal contraction. The less severely injured patients appeared to have a greater beneficial drug effect. Evidence against an effect of Sygen was minimal and scattered.. Although not proven in the primary efficacy analysis of this trial, Sygen appears to be beneficial in patients with severe spinal cord injury.

Topics: Acute Disease; Adolescent; Adult; Aged; Double-Blind Method; Female; G(M1) Ganglioside; Humans; Logistic Models; Male; Middle Aged; Neuroprotective Agents; Prospective Studies; Recovery of Function; Spinal Cord Injuries; Treatment Outcome

Spinal cord injury remains with limited natural recovery and only a few general ineffective treatment options. Recent publications have reported enhanced neurologic recovery with the use of methylprednisolone and GM-1 ganglioside. The results of the Maryland GM-1 Ganglioside Study reported a significant drug effect with respect to the fraction of patients that had a change of two or more Frankel grades from entrance into the study to 1-year follow-up. This study formed the basis for the currently ongoing larger placebo-controlled multicentered study using Sygen GM-1 following acute spinal cord injury. This study has entered 797 patients and is expected to present results in early 1998.

Topics: Adult; Drug Therapy, Combination; Female; Follow-Up Studies; G(M1) Ganglioside; Humans; Male; Methylprednisolone; Middle Aged; Neuroprotective Agents; Patient Selection; Placebos; Spinal Cord Injuries; Time Factors

In a randomized double-blind cross-over study, humans with chronic spinal cord injury received ganglioside GM-1 or placebo for 2 months. GM-1, administered intravenously at a dose of 100 mg, 6 days a week, resulted in a statistically significant improvement of motor scores (P < 0.05), whether administered before or after 2 months of placebo. There was no placebo effect on motor scores. Subjects who received GM-1 before placebo maintained their improvement during the placebo phase. Subjects who received GM-1 ambulated with a reciprocal gait, using orthotics, for longer distances and at a faster rate whether the drug was administered before or after placebo. These results constitute the first finding that any chemical substance improves locomotion in human chronic spinal cord injury.

Topics: Adult; Chronic Disease; Combined Modality Therapy; Double-Blind Method; Female; G(M1) Ganglioside; Humans; Male; Muscles; Physical Therapy Modalities; Spinal Cord Injuries; Walking

Neurological deficit resulting from spinal cord injury varies widely in severity, ranging from transient abnormal reflexes to lifelong complete absence of motor and sensory function. Medical treatment to aid damaged neurons to recover function has been very limited; therapeutic efforts have focused primarily on initial stabilization of fractures, hemodynamic resuscitation, and then aggressive rehabilitation to enhance the full development of any remaining neuronal activity. Pharmacological treatment to improve restoration of neurological function may be possible, however, as indicated by many animal studies and a few clinical studies with a number of agents. A recent clinical trial of GM-1 ganglioside conducted in patients with spinal cord injuries showed that GM-1 ganglioside enhanced the recovery of neurological function 1 year after major spinal cord injury. In addition to GM-1 ganglioside treatment, these patients received aggressive medical and surgical treatment, as well as methylprednisolone. Neurological recovery was assessed with the Frankel scale and the American Spinal Injury Association (ASIA) motor scale. The findings show enhanced motor recovery compared with placebo in the lower extremities, but not in the upper extremities, over time. This corresponds to improved function of axons passing through the site of injury. Analysis of individual motor groups showed that neurological recovery in the GM-1 ganglioside-treated patients increased in initially paralyzed muscles, enabling them to regain useful motor function; paretic muscles were not found to be strengthened. The study provides the basis for larger studies of GM-1 ganglioside and methylprednisolone, which are currently under way.

Topics: Double-Blind Method; Drug Therapy, Combination; G(M1) Ganglioside; Humans; Methylprednisolone; Prospective Studies; Psychomotor Performance; Spinal Cord Injuries

Two recent prospective, randomized, placebo-controlled, double-blinded clinical drug studies in acute spinal cord injury have reported enhancement of neurologic recovery of motor function. The drugs investigated in these studies were methylprednisolone and GM-1 ganglioside. Before these studies, the treatment of patients with spinal cord injuries had been restricted to prevention of further injury to the spinal cord, limiting secondary damage following the initial injury, increasing the patient's ability to function through intensive rehabilitation, and facilitating any spontaneous recovery of neurologic function. Methylprednisolone is a steroid administered at very high levels, and GM-1 is a complex acidic glycolipid found at high levels in cell membranes in the mammalian central nervous system with known neuroprotective and neurofunctional restoration potential. This article summarizes the previously reported Maryland GM-1 clinical trial and presents the clinical and statistical design of a larger clinical trial being conducted with the purpose of verifying a beneficial GM-1 drug effect when administered with methylprednisolone in acute spinal cord injury.

Topics: Critical Care; Double-Blind Method; G(M1) Ganglioside; Humans; Methylprednisolone; Prospective Studies; Spinal Cord Injuries; Trauma Centers

Topics: Catheterization, Central Venous; Double-Blind Method; G(M1) Ganglioside; Humans; Infections; Quadriplegia; Spinal Cord Injuries

Spinal cord injury is typically a devastating injury with no or only limited neurologic recovery. Recent papers have reported enhancement of neurologic recovery following spinal cord injury with both methylprednisolone and GM-1 ganglioside. This paper provides additional details of the GM-1 study and a further analysis of recovery of motor function for each of the ten neurologic levels assessed in the study. This additional analysis provides further evidence that the largest enhanced recovery of motor function in the GM-1 treatment group occurred in the muscles of the lower extremities and is consistent with the enhanced recovery occurring in the white matter tracts passing through the level of injury.

Topics: Adult; Female; Follow-Up Studies; G(M1) Ganglioside; Humans; Male; Motor Activity; Muscles; Prospective Studies; Spinal Cord Injuries

Spinal cord injury is typically a devastating injury with no or only limited neurologic recovery. Recent papers have reported enhancement of neurologic recovery following spinal cord injury with both methylprednisolone and GM-1 ganglioside. This paper provides additional details of the GM-1 study and a further analysis of recovery of motor function for each of the ten neurologic levels assessed in the study. This additional analysis provides further evidence that the largest enhanced recovery of motor function in the GM-1 treatment group occurred in the muscles of the lower extremities and is consistent with the enhanced recovery occurring in the white matter tracts passing through the level of injury.

Topics: Adult; Carbohydrate Sequence; Double-Blind Method; Female; Follow-Up Studies; G(M1) Ganglioside; Humans; Male; Molecular Sequence Data; Prospective Studies; Spinal Cord Injuries

Topics: G(M1) Ganglioside; Humans; Research Design; Spinal Cord Injuries

Topics: G(M1) Ganglioside; Humans; Polyradiculoneuropathy; Spinal Cord Injuries

Topics: Cost-Benefit Analysis; G(M1) Ganglioside; Humans; Spinal Cord Injuries

Topics: G(M1) Ganglioside; Humans; Motor Activity; Spinal Cord Injuries

Spinal-cord injury is devastating; until recently, there was no medical treatment to improve recovery of the initial neurologic deficit. Studies in animals have shown that monosialotetrahexosylganglioside (GM-1) ganglioside enhances the functional recovery of damaged neurons.. A prospective, randomized, placebo-controlled, double-blind trial of GM-1 ganglioside was conducted in patients with spinal-cord injuries. Of 37 patients entered into the study, 34 (23 with cervical injuries and 11 with thoracic injuries) completed the test-drug protocol (100 mg of GM-1 sodium salt or placebo intravenously per day for 18 to 32 doses, with the first dose taken within 72 hours of the injury) and a one-year follow-up period. Neurologic recovery was assessed with the Frankel scale (comprising five categories) and the American Spinal Injury Association (ASIA) motor score (a scale of scores from 0 to 100, derived from strength tests of 20 specific muscles, each scored from 0 to 5).. There was a significant difference between groups in the distribution of improvement of Frankel grades from base line to the one-year follow-up (improvement of 0, 1, 2, and 3 grades in 13, 4, 1, and 0 patients, respectively, in the placebo group and 8, 1, 6, and 1 patients, respectively, in the GM-1 group; P = 0.034 by the Cochran-Mantel-Haenszel chi-square test). The GM-1-treated patients also had a significantly greater mean improvement in ASIA motor score from base line to the one-year follow-up than the placebo-treated patients (36.9 vs. 21.6 points; P = 0.047 by analysis of covariance with the base-line ASIA motor score as the covariate). An analysis of individual muscle recoveries revealed that the increased recovery in the GM-1 group was attributable to initially paralyzed muscles that regained useful motor strength rather than to strengthening of paretic muscles.. This small study provides evidence that GM-1 enhances the recovery of neurologic function after one year. A larger study must be conducted, however, before GM-1 is considered efficacious and safe in treating spinal-cord injury.

Topics: Adolescent; Adult; Drug Administration Schedule; Female; Follow-Up Studies; G(M1) Ganglioside; Humans; Injections, Intravenous; Middle Aged; Motor Activity; Neurologic Examination; Prospective Studies; Spinal Cord Injuries

A prospective, randomized, placebo-controlled, double-blinded spinal cord injury GM1 ganglioside drug trial was completed. Of the 37 patients entered over a 16 month period, 34 patients (23 cervical and 11 thoracic injuries) received the test drug protocol and completed the one year follow up period. The neurologic recovery was quantified by serial measurement of the ASIA motor score throughout the acute hospital course and one year long follow up period. The primary variable used to assess neurologic recovery was the difference in the ASIA motor score from the admission value to the value at one year. The GM1 group had an average motor recovery of 36.9 points whereas the placebo group had an average change of 21.6 points (t-test difference, p = 0.088). Analysis of the secondary variable, the area under the ASIA motor score versus the logarithm of time, and the use of rank order nonparametric statistic on both the primary and secondary variables to sort neurologic recovery obtained similar statistical differences between the GM1 and placebo treatment groups. Randomization imbalances in baseline severity of injury and division of cervical and thoracic injury occurred in the trial. Because of this fact and the small sample size of the study verification of these results by a larger study is required.

Topics: Double-Blind Method; G(M1) Ganglioside; Humans; Prospective Studies; Spinal Cord Injuries

The aim of this study was to evaluate the best timing and feasibility of intrathecal application of sodium monosialoganglioside (GM1) after spinal cord contusion in Wistar rats as an experimental model.. Forty Wistar rats were submitted to contusion spinal cord injury after laminectomy. The animals were randomized and divided into four groups: Group 1 - Intrathecal application of GM1 24 hours after contusion; Group 2 - Intrathecal application of GM1 48 hours after contusion; Group 3 - intrathecal application of GM1 72 hours after contusion; Group 4 - Sham, with laminectomy and intrathecal application of 0.5 mL of 0.9% saline solution, without contusion. The recovery of locomotor function was evaluated at seven different moments by the Basso, Beattie, and Bresnahan (BBB) test. They were also assessed by the horizontal ladder, with sensory-motor behavioral assessment criteria, pre-and postoperatively.. This experimental study showed better functional scores in the group submitted to the application of GM1, with statistically significant results, showing a mean increase when evaluated on known motor tests like the horizontal ladder and BBB, at all times of evaluation (p < 0.05), especially in group 2 (48 hours after spinal cord injury). Also, fewer mistakes and slips over the horizontal ladder were observed, and many points were achieved at the BBB scale analysis.. The study demonstrated that the intrathecal application of GM1 after spinal cord contusion in Wistar rats is feasible. The application 48 hours after the injury presented the best functional results.

Topics: Animals; Contusions; Disease Models, Animal; G(M1) Ganglioside; Rats; Rats, Wistar; Recovery of Function; Spinal Cord; Spinal Cord Injuries

Predictors of the central nervous system (CNS) directed autoantibody response after acute CNS injury are poorly understood. We analyzed titers of IgG and IgM autoantibodies to ganglioside GM1 in serial serum specimens collected from human patients following acute spinal cord injury (SCI), traumatic brain injury (TBI) and brain tumor resection. We also assessed putative predictors of the autoantibody titers. We enrolled 19 patients with acute SCI, 14 patients with acute severe TBI, and 19 patients undergoing brain tumor resection. We also enrolled 25 control subjects. Some SCI, TBI and tumor patients exhibited elevated IgG titers as compared with control values; some SCI and TBI patients exhibited an acute peak in IgG titers, most commonly 14 days after insult. Some clinical and radiographic measures of injury severity correlated with IgG titer elevation in SCI and TBI patients but not tumor patients. Our study demonstrates that diverse CNS insults are followed by increased IgG autoimmune antibody titers to the CNS antigen ganglioside GM1, however the response inherent to each insult type is unique. IgG autoimmune antibody titers to GM1 merit further study as a biomarker of traumatic injury severity that can be measured in delayed fashion after CNS insult. These human data help to inform which patients with CNS insults are at risk for CNS-directed autoimmunity as well as the time course of the response.

Topics: Autoantibodies; Brain Injuries, Traumatic; Brain Neoplasms; Central Nervous System; G(M1) Ganglioside; Humans; Immunoglobulin G; Spinal Cord Injuries

To investigate the effects of ganglioside [monostalotetra-hexosylganglioside (GM1)] on the expressions of caspase-3 and nerve growth factor (NGF) in rats with acute spinal cord injury (SCI).. Male Sprague- Dawley (SD) rats were selected and randomly divided into Sham group, SCI group and GM1 administration group. The rats in Sham group, SCI group and GM1 group were subjected to behavioral examinations of Basso Beattie Bresnahan (BBB) and oblique-plate test at 1, 7 and 14 d after operation. The content of methylene dioxyamphetamine (MDA) and the activity of superoxide dismutase (SOD) of every rat in each group were measured by enzyme-linked immunosorbent assay (ELISA). Immunofluorescence staining assay was used to detect the expression levels of caspase-3 and NGF of rats in each group. The messenger ribonucleic acid (mRNA) and protein expressions of caspase-3 and NGF of rats in Sham group, SCI group and GM1 group were detected using reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blotting assay.. The BBB scores and the results of oblique-plate test in Sham group, SCI group and GM1 group at 1, 7 and 14 d showed that the BBB scores and the results of oblique-plate test of rats in each group were significantly decreased at 1 d after SCI, and had different degrees of recovery at 7 and 14 d after injury. The results of ELISA detection revealed that SCI group had increased content of MDA and clearly decreased activity of SOD in comparison with Sham group; at the same time, MDA content in GM1 group was overtly lower than that in SCI group, while SOD activity was enhanced evidently in GM1 group compared with that in SCI group. According to immunofluorescence assay, significantly increased expression of caspase-3 and distinctly decreased expression of NGF were found in SCI group. However, this phenomenon was significantly reversed by GM1. RT-PCR and Western blotting assay severally proved that the mRNA and protein expressions of caspase-3 were raised in SCI group and decreased clearly after the administration of GM1; while the mRNA and protein expressions of NGF was significantly reduced in SCI group and overtly elevated after the administration of GM1. ANOVA showed that there were statistically significant differences in expressions of caspase-3 and NGF among Sham group, SCI group and GM1 group (p<0.05).. GM1 has an evident effect on the expressions of caspase-3 and NGF in rats with acute SCI, and is able to down-regulate the expression of caspase-3 and up-regulate the expression of NGF, so as to achieve its therapeutic effect on SCI.

Topics: Acute Disease; Animals; Caspase 3; G(M1) Ganglioside; Male; Nerve Growth Factor; Rats; Rats, Sprague-Dawley; Spinal Cord Injuries; Superoxide Dismutase

Therapeutic strategies for the spinal cord injury (SCI) are limited by the current available drug delivery techniques. Here, an in situ gelling drug delivery system (DDS), composed of a Poloxamer-407, a 188 mixture-based thermoresponsive hydrogel matrix and, an incorporated therapeutic compound (monosialoganglioside, GM1), is developed for SCI therapy. A low-thoracic hemisection in rats is used as SCI model to evaluate therapeutic efficiency. The GM1-incorporating Poloxamer-407 and 188 polymer solution is converted to a hydrogel (GM1-hydrogel) upon instillation to the injured spinal cord, due to the increased temperature. At body temperature, the thermoresponsive hydrogel prolongs the release of GM1 for about 1 month, due to the superposition of dissolution and swelling (anomalous transport) of the hydrogel matrix. The sustained release of the GM1-hydrogel enables the prolonged residence time of GM1 at the injured spinal cord, decreases the frequency of administration and, consequently, may improve patient compliance. After SCI, the administration of GM1-hydrogel to the lesion site inhibits the apoptotic cell death and glial scar formation, enhances the neuron regeneration, provides neuroprotection to the injured spinal cord, and improves the locomotor recovery. Overall, this study opens future perspectives for the treatment of SCI with a prolonged drug release DDS.

Topics: Animals; Delayed-Action Preparations; G(M1) Ganglioside; Hydrogels; Male; Poloxamer; Rats; Rats, Sprague-Dawley; Spinal Cord Injuries

To evaluate the functional and histological effects of ganglioside G(M1) and erythropoietin after experimental spinal cord contusion injury.. Fifty male Wistar rats underwent experimental spinal cord lesioning using an NYU-Impactor device and were randomly divided into the following groups, which received treatment intraperitoneally. The G(M1) group received ganglioside G(M1) (30 mg/kg); the erythropoietin group received erythropoietin (1000 IU/kg); the combined group received both drugs; and the saline group received saline (0.9%) as a control. A fifth group was the laminectomy group, in which the animals were subjected to laminectomy alone, without spinal lesioning or treatment. The animals were evaluated according to the Basso, Beattie and Bresnahan (BBB) scale, motor evoked potential recordings and, after euthanasia, histological analysis of spinal cord tissue.. The erythropoietin group had higher BBB scores than the G(M1) group. The combined group had the highest BBB scores, and the saline group had the lowest BBB scores. No significant difference in latency was observed between the three groups that underwent spinal cord lesioning and intervention. However, the combined group showed a significantly higher signal amplitude than the other treatment groups or the saline group (p<0.01). Histological tissue analysis showed no significant difference between the groups. Axonal index was significantly enhanced in the combined group than any other intervention (p<0.01).. G(M1) and erythropoietin exert therapeutic effects on axonal regeneration and electrophysiological and motor functions in rats subjected to experimental spinal cord lesioning and administering these two substances in combination potentiates their effects.

Topics: Animals; Drug Therapy, Combination; Erythropoietin; G(M1) Ganglioside; Injections, Intraperitoneal; Locomotion; Male; Models, Animal; Necrosis; Neuroprotective Agents; Random Allocation; Rats, Wistar; Reaction Time; Recovery of Function; Spinal Cord Injuries

Brachial plexus root avulsion (BPRA) leads to dramatic motoneuron death and glial reactions in the corresponding spinal segments at the late stage of injury. To protect spinal motoneurons, assessment of the affected spinal segments should be done at an earlier stage of the injury. In this study, we employed 18F-FDG small-animal PET/CT to assess the severity of BPRA-induced cervical spinal cord injuries. Adult Sprague-Dawley rats were randomly treated and divided into three groups: Av+NS (brachial plexus root avulsion (Av) treated with normal saline), Av+GM1 (treated with monosialoganglioside), and control. At time points of 3 day (d), 1 week (w), 2 w, 4 w and 8 w post-injury, 18F-FDG micro-PET/CT scans and neuropathology assessments of the injured spinal roots, as well as the spinal cord, were performed. The outcomes of the different treatments were compared. The results showed that BPRA induced local bleeding and typical Wallerian degeneration of the avulsed roots accompanied by 18F-FDG accumulations at the ipsilateral cervical intervertebral foramen. BPRA-induced astrocyte reactions and overexpression of neuronal nitric oxide synthase in the motoneurons correlated with higher 18F-FDG uptake in the ipsilateral cervical spinal cord during the first 2 w post-injury. The GM1 treatment reduced BPRA-induced astrocyte reactions and inhibited the de novo nNOS expressions in spinal motoneurons. The GM1 treatment also protected spinal motoneurons from avulsion within the first 4 w post-injury. The data from this study suggest that 18F-FDG PET/CT could be used to assess the severity of BPRA-induced primary and secondary injuries in the spinal cord. Furthermore, GM1 is an effective drug for reducing primary and secondary spinal cord injuries following BPRA.

Topics: Accessory Nerve Injuries; Animals; Brachial Plexus; G(M1) Ganglioside; Glucose-6-Phosphate; Male; Motor Neurons; Positron-Emission Tomography; Rats; Rats, Sprague-Dawley; Spinal Cord; Spinal Cord Injuries; Time Factors; X-Ray Microtomography

After three decades of clinical research on interventions to improve neurological outcomes in persons with spinal cord injury (SCI), the promise of preclinical discovery has yet to be translated into a consensus standard of care treatment. Nonetheless, SCI researchers remain hopeful that advances in preclinical discovery coupled with improved clinical trial performance will yield effective restorative treatment. This historical review of key studies in SCI over the past 30 years illustrates the progress that has been achieved in establishing a high standard in the conduct of clinical research while providing important lessons for improving trial design, conduct and reporting. Through application of these lessons, the performance of SCI trials can be improved, thereby shortening the pathway to successful translation and the development of effective therapies.

Topics: Anti-Inflammatory Agents; Cell- and Tissue-Based Therapy; Clinical Trials as Topic; G(M1) Ganglioside; History, 20th Century; History, 21st Century; Humans; Methylprednisolone; Patient Care; Publication Bias; Randomized Controlled Trials as Topic; Spinal Cord Injuries; Translational Research, Biomedical

Experimental, controlled, animal study.. To evaluate the effect of GM1 ganglioside, hyperbaric oxygen and both in combination, in the treatment of experimental spinal cord lesions in rats.. Brazil.. Thirty-two Wistar rats with spinal cord lesions were divided into four groups: one group received GM1 ganglioside, one was submitted to hyperbaric oxygen therapy (HBOT), the third received both treatments and the fourth received no treatment (control).. There were no significant differences between the groups in the histological analysis, for any of the variables (necrosis, hemorrhage, hyperemia, cystic degeneration, P>0.06). Neither were there any significant differences in the comparison of left and right sides in the functional tests (P>0.06 for all). No significant differences were found in the locomotor ratings, in the comparison of groups at 2, 7, 21 and 28 days after the surgical procedure. However, in the evaluation on day 14, group 3, which received the combined therapy, showed a significantly higher Basso Beattie and Bresnahan score than the other groups (P=0.015).. The therapeutic effect of GM1 in locomotor evaluation of rats submitted to spinal cord lesion is anticipated by HBOT.

Topics: Acute Disease; Animals; Combined Modality Therapy; Disease Models, Animal; G(M1) Ganglioside; Hyperbaric Oxygenation; Male; Nerve Regeneration; Neuroprotective Agents; Rats; Rats, Wistar; Spinal Cord Injuries

The pharmacological effects of methylprednisolone (MP) and ganglioside GM-1 on spinal injuries have been thoroughly investigated, but only a few studies have evaluated the interaction between these two drugs.. Twenty-four Wistar rats were subjected to contusive injury of the spinal cord produced by the NYU system. These animals were divided into four groups: group I was injected with MP; group II was injected with GM-1; group III was injected with MP together with GM-1; and group control received physiological serum. The animals were evaluated with regard to their recovery of locomotive function by means of the BBB test on the second, seventh and fourteenth days after receiving the contusive injury to the spinal cord. They were sacrificed on the fourteenth day.. This study demonstrated that the MP and GM-1 groups presented functional results that were better than those of the control group, although the enhanced recovery of group II (GM-1) relative to the control group was not statistically significant (p>0.05). The most notable recovery of locomotive function was observed in the group that received MP alone (p<0.05). The group that received MP together with GM-1 presented results that were better than those of the control group (p<0.05).. Administration of methylprednisolone alone or with GM-1 was shown to be effective for recovery of locomotive function. Combined administration of these drugs resulted in better outcomes than administration of methylprednisolone alone.

Topics: Animals; Anti-Inflammatory Agents; Disease Models, Animal; Drug Evaluation, Preclinical; Drug Therapy, Combination; G(M1) Ganglioside; Male; Methylprednisolone; Motor Activity; Rats; Rats, Wistar; Recovery of Function; Spinal Cord Injuries; Statistics, Nonparametric; Treatment Outcome

To determine the serum cytokine profiles of patients with spinal cord injury (SCI) and varying clinical presentations relative to healthy, able-bodied, age-matched control subjects.. Cross-sectional study.. Clinical research unit.. People with SCI (N=56) and different clinical presentations, and healthy, able-bodied, age-matched control subjects (N=35).. Not applicable.. Serum levels of the proinflammatory cytokines interleukin (IL) 1beta, IL-6, tumor necrosis factor alpha (TNF-alpha), the anti-inflammatory cytokines IL-4 and IL-10, the regulatory cytokine IL-2, the IL-1 receptor antagonist (IL-1RA), and autoantibodies against myelin-associated glycoprotein and GM(1) ganglioside (anti-GM(1)) immunoglobulin (IgG and IgM), as determined by enzyme-linked immunosorbent assay. The relationship between elevated serum cytokine levels and clinical variables was also studied.. SCI subjects exhibited serum concentrations of IL-6, TNF-alpha, IL-1RA, and anti-GM(1) (IgG) that were greater (P<.05) than control group values. Elevated cytokine concentrations were not associated with high white blood cell counts, level of injury, or American Spinal Injury Association classification; they were evident in SCI subjects who were asymptomatic for medical complications, but were further elevated in subjects with pain, urinary tract infection (UTI), and pressure ulcers.. Elevated levels of circulating proinflammatory cytokines and autoantibodies are present in the serum of SCI subjects without medical complications, and are further elevated in SCI subjects with neuropathic pain, UTI, or pressure ulcers, relative to healthy, able-bodied control subjects. These findings may be indicative of a protective autoimmunity, simply a consequence of occult or evident infection, or evidence of cytokine dysregulation that may contribute to an immune-mediated impairment of axonal conduction.

Topics: Adult; Autoantibodies; Cervical Vertebrae; Cross-Sectional Studies; Cytokines; Enzyme-Linked Immunosorbent Assay; Female; G(M1) Ganglioside; Humans; Interleukin 1 Receptor Antagonist Protein; Interleukin-8; Male; Myelin-Associated Glycoprotein; Paraplegia; Pressure Ulcer; Quadriplegia; Reference Values; Spinal Cord Injuries; Thoracic Vertebrae; Tumor Necrosis Factor-alpha; Urinary Tract Infections

This study characterized the proinflammatory cytokines, interleukin-2 (IL-2) and tumor necrosis factor alpha (TNFalpha), the antiinflammatory cytokines, IL-4 and IL-10, autoantibodies specific for GM1 ganglioside (anti-GM1), IgG and IgM, and myelin-associated glycoprotein (anti-MAG), in the sera of infection-free, chronic (>12 months), traumatically injured SCI patients (n = 24). Healthy able-bodied subjects (n = 26) served as controls. The proinflammatory cytokines and anti-GM1 antibodies were of particular interest as they have been implicated in an autoimmune "channelopathy" component to central and peripheral conduction deficits in various chronic neuroinflammatory diseases. Antibody and cytokine titers were established using enzyme-linked immunosorbent assays (ELISA). The mean anti-GM(1) (IgM) titer value for the SCI group was significantly higher (p < 0.05) than controls. The SCI group also demonstrated significantly higher titers (p < 0.05) of IL-2 and TNF alpha than controls. No differences were found between the SCI group and control group mean levels of IL-4 or IL-10. Overall, the serum of 57% of SCI patients contained increased levels of autoantibodies or proinflammatory cytokines relative to control values. These results provide preliminary support for the hypothesis that chronic immunological activation in the periphery occurs in a subpopulation of chronic SCI patients. It remains to be established whether elevated serum titers of proinflammatory cytokines and autoantibodies against GM1 are beneficial to the patients or whether they are surrogate markers of a channelopathy that compounds the neurological impairment associated with traumatic axonopathy or myelinopathy.

Topics: Adult; Autoantibodies; B-Lymphocytes; Chronic Disease; Female; G(M1) Ganglioside; Humans; Interleukin-10; Interleukin-2; Interleukin-4; Male; Middle Aged; Myelin-Associated Glycoprotein; Spinal Cord Injuries; Tumor Necrosis Factor-alpha

Topics: Clinical Trials as Topic; G(M1) Ganglioside; Humans; Methylprednisolone; Spinal Cord Injuries

Post hoc secondary analysis of data from 1992 to 1998 in the trial of Sygen in Acute Spinal Cord Injury.. Quasi-epidemiologic understanding of injury and treatment patterns and of recruitment in an SCI trial. No drug efficacy results.. The most recent large epidemiologic study was the National SCI Database by Stover and colleagues around 1980.. Emphasis on descriptive, rather than inferential, statistics: consistent with secondary analysis.. The study involved 760 patients at 28 centers in North America. Cervical injuries were more common than thoracic, and complete injuries were more common than incomplete injuries. Recruitment in the complete cervical stratum was 332, but the incomplete thoracic strata had only 31 patients combined. Vital signs at arrival and on randomization show fair stability. Clock times show more injuries on weekends and nights but suggest immediate attention was given. Elapsed times to treatment (especially EMT and Medevac arrival) are short. The rate of direct admission to tertiary centers, traction weight, and time to surgery vary among centers. Inpatient rehabilitation appeared driven by insurance in addition to severity.. The imbalances in favor of cervical and of complete injuries would make it hard for studies to attain results for SCI in general. The vital signs and time patterns suggest local protocol-driven stabilization to prevent secondary physiologic injury early after SCI. Some features of care vary among centers, but the sparseness of prospective data in specific injury and treatment categories suggests that treatment guidelines have limited empirical support and should be made cautiously.

Topics: Acute Disease; Adolescent; Adult; Aged; Decompression, Surgical; Female; G(M1) Ganglioside; Humans; Male; Middle Aged; Neuroprotective Agents; North America; Patient Selection; Randomized Controlled Trials as Topic; Retrospective Studies; Spinal Cord Injuries; Time Factors

Post hoc, secondary analysis of data from 1992 to 1998 in the trial of Sygen in acute spinal cord injury.. Quasi-epidemiologic understanding of measurement tools and of recovery patterns. No drug efficacy results.. Many authors have studied individual scales for measuring the severity of spinal cord injury.. Emphasis on descriptive, rather than inferential, statistics: consistent with secondary analysis.. Of the 760 patients, 43 died within 365 days. The rate was higher for complete injuries (7.1% vs. 3.2%, P = 0.017). Marked recovery at 26 weeks was more frequent in those with better baseline American Spinal Injury Association (ASIA) Impairment Scale (AIS) scores, but was not different for methylprednisolone within versus after 3 hours. Light touch scores improved at each visit, more so in those with higher scores at baseline. Bladder control similarly improved. Motor and sensory scores exhibited departures from assumptions underlying normal-theory statistical techniques: t test and analysis of variance. Furthermore, they were mixtures of differing distributions from different study strata, so that overall conclusions depend on the mixture of patients seen.. The prognosis of these patients with spinal cord injury seen at 28 centers in North America during the mid-1990s appears better than was often assumed earlier. The general patterns are similar across different measurement scales, although there are intriguing differences. The patterns in different strata are different in specifics, and complete injuries do less well. Pooling data from different strata may result in probability distributions that depart from normal-theory assumptions and give misleading results depending on recruitment patterns.

Topics: Adolescent; Adult; Aged; Female; G(M1) Ganglioside; Humans; Male; Middle Aged; Neuroprotective Agents; North America; Prognosis; Randomized Controlled Trials as Topic; Recovery of Function; Retrospective Studies; Severity of Illness Index; Spinal Cord Injuries

Topics: Acute Disease; G(M1) Ganglioside; Humans; Multicenter Studies as Topic; Neuroprotective Agents; Randomized Controlled Trials as Topic; Spinal Cord Injuries; Treatment Outcome

Topics: Anti-Inflammatory Agents; Clinical Trials as Topic; Drug Therapy, Combination; G(M1) Ganglioside; Humans; Methylprednisolone; Neuroprotective Agents; Pregnatrienes; Spinal Cord Injuries; Treatment Outcome

Topics: Adult; Cervical Vertebrae; Emergency Medical Services; Football; G(M1) Ganglioside; Humans; Joint Dislocations; Lipid Peroxidation; Male; Methylprednisolone; Radiography; Resuscitation; Spinal Cord Compression; Spinal Cord Injuries; Spinal Fractures

Topics: Chronic Disease; G(M1) Ganglioside; Humans; Spinal Cord Injuries

Recent clinical trials have reported that methylprednisolone sodium succinate (MP) or the monosialic ganglioside GM1 improves neurological recovery in human spinal cord injury. Because GM1 may have additive or synergistic effects when used with MP, the authors compared MP, GM1, and MP+GM1 treatments in a graded rat spinal cord contusion model. Spinal cord injury was caused by dropping a rod weighing 10 gm from a height of 1.25, 2.5, or 5.0 cm onto the rat spinal cord at T-10, which had been exposed via laminectomy. The lesion volumes were quantified from spinal cord Na and K shifts at 24 hours after injury and the results were verified histologically in separate experiments. A single dose of MP (30 mg/kg), given 5 minutes after injury, reduced 24-hour spinal cord lesion volumes by 56% (p = 0.0052), 28% (p = 0.0065), and 13% (p > 0.05) in the three injury-severity groups, respectively, compared to similarly injured control groups treated with vehicle only. Methylprednisolone also prevented injury-induced hyponatremia and increased body weight loss in the spine-injured rats. When used alone, GM1 (10 to 30 mg/kg) had little or no effect on any measured variable compared to vehicle controls; when given concomitantly with MP, GM1 blocked the neuroprotective effects of MP. At a dose of 3 mg/kg, GM1 partially prevented MP-induced reductions in lesion volumes, while 10 to 30 mg/kg of GM1 completely blocked these effects of MP. The effects of MP on injury-induced hyponatremia and body weight loss were also blocked by GM1. Thus, GM1 antagonized both central and peripheral effects of MP in spine-injured rats. Until this interaction is clarified, the authors recommend that MP and GM1 not be used concomitantly to treat acute human spinal cord injury. Because GM1 modulates protein kinase activity, protein kinases inhibit lipocortins, and lipocortins mediate anti-inflammatory effects of glucocorticoids, it is proposed that the neuroprotective effects of MP are partially due to anti-inflammatory effects and that GM1 antagonizes the effects of MP by inhibiting lipocortin. Possible beneficial effects of GM1 reported in central nervous system injury may be related to the effects on neural recovery rather than acute injury processes.

Topics: Animals; Annexins; Body Water; Body Weight; Drug Synergism; G(M1) Ganglioside; Hematocrit; Hyponatremia; Male; Methylprednisolone; Potassium; Rats; Reference Values; Sodium; Spinal Cord Injuries

Topics: Drug Administration Schedule; G(M1) Ganglioside; Humans; Methylprednisolone Hemisuccinate; Spinal Cord Injuries

Topics: Drugs, Investigational; Football; G(M1) Ganglioside; Humans; Male; Spinal Cord Injuries

In this study we examined the effect of chronic GM-1 ganglioside treatment on the reestablishment of axonal continuity and functional recovery in spinal cord-transected rats. Previous studies have shown that chronic treatment with GM-1 ganglioside is effective in producing regeneration of lesioned mesostriatal dopaminergic neurons in the central nervous system [1, 2]. In addition, GM-1 ganglioside advances peripheral nerve regeneration following nerve crush injury [12]. Axonal continuity was determined by the ability of the spinal cord to transport horseradish peroxidase across the region of transection. Comparisons between ganglioside-treated and saline-treated controls showed that ganglioside treatment resulted in the reestablishment of axonal continuity between the spinal cord distal to the level of the transection and the brainstem. Saline-treated controls showed little evidence of axonal continuity between these two regions. Thus gangliosides induce reestablishment of axonal continuity and thereby could advance functional recovery in rats following spinal cord transection.

Topics: Animals; Axonal Transport; Female; G(M1) Ganglioside; Rats; Rats, Inbred Strains; Spinal Cord Injuries; Wound Healing

The effect of GM1 ganglioside on the recovery of dopaminergic nigro-striatal neurons was studied in rats after unilateral hemitransection. GM1 treatment favoured the collateral sprouting of dopaminergic axons in the striatum as indicated by the induced increase of tyrosine hydroxylase (TH) activity and immunofluorescence. Concomitantly GM1 partially prevented the decrease of TH activity caused by the hemitransection in the substantia nigra ipsilateral to the lesion. A significant increase of TH immunoreactivity was also detected in the substantia nigra: GM1 prevented the disappearance of TH-positive cell bodies and increased the formation of TH-positive collaterals and dendrites with respect to the saline treatment. The addition of GM1 to embryonic dissociated mesencephalic cell cultures stimulates the expression of dopaminergic characteristics as suggested by the increase of 3H-DA uptake.

Topics: Animals; Brain; Brain Injuries; Cell Differentiation; Corpus Striatum; Dopamine; G(M1) Ganglioside; Gangliosides; Nerve Regeneration; Neurons; Rats; Spinal Cord Injuries