Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0599766 (functional recovery)
 13,441 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Monosialogangliosides, neuroprotection, and neuronal repair processes. 161 10

The effects of GM1 ganglioside administration on functional recovery and recovery of caudate nucleus dopamine levels have been assessed in cats made parkinsonian by administration of the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Cats made severely parkinsonian by MPTP administration began to show spontaneous functional recovery by the third week after MPTP, as had been observed in previous studies with this model. In contrast, cats with similar initial impairment but which received 3 weeks of GM1 ganglioside treatment (30 mg/kg, i.p. daily) showed an accelerated behavioral recovery, showing significant functional improvement after the first week of GM1 treatment and almost normal function by the end of the third week of treatment. The GM1-treated cats had caudate nucleus dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC), and HVA levels significantly increased above levels measured in saline-treated MPTP control cats. A second group of cats received MPTP only until the first signs of parkinsonism were observed and thus overall had a less severe initial syndrome than the cats described previously. Again, while all cats showed functional recovery over time, the recovery process was accelerated in GM1-treated cats. GM1 treatment also caused a significant increase in caudate dopamine levels in these cats. These results suggest that GM1 ganglioside administration can result in increased dopamine levels even in the heavily denervated striatum and accelerate functional recovery after an MPTP-induced lesion of the nigrostriatal dopamine system in the cat. This suggests that GM1 or other trophic factor therapies may be fruitful treatment strategies for a disorder of nigrostriatal function such as Parkinson's disease.
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PMID:MPTP-induced parkinsonism: acceleration of biochemical and behavioral recovery by GM1 ganglioside treatment. 161 17

In vitro studies have shown that monosialoganglioside GM1 reduces excitatory amino acid-related neurotoxicity by limiting the downstream consequences of abusive excitatory amino acid receptor stimulation, while enhancing neuronotrophic factor action in a variety of neuronal cell types. Systemic administration of GM1 appears to be efficacious in reducing acute nerve cell damage and in facilitating medium- and long-term functional recovery after brain injury. Although the mechanism of action remains unclear, it appears likely that GM1 protective effects in the acute injury phase are at least in part due to the attenuation of excitotoxicity, while the long-term functional recovery might reflect GM1 potentiation of neuronotrophic factors. The potential therapeutic efficacy of GM1 administration in different conditions in humans, as suggested by pioneer clinical studies, is reviewed. Further larger, randomized, double-blind clinical studies are necessary to define the therapeutic efficacy.
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PMID:Monosialoganglioside GM1 in cerebral ischemia. 185 96

Neonatal rats, when spinalized on the fourteenth postnatal day, showed minimal recovery of function in their hindlimbs. Bridging the cut spinal cord with E16 fetal spinal cord tissue did not improve functional recovery. Bridging, plus treatment with GM1 ganglioside, caused a significant (p less than 0.05) improvement in function, versus the bridged animals treated with saline. The E16 spinal cord transplants survived poorly, or not at all. Contact of the hindlimbs with a surface is necessary to elicit function. Regrowth of descending fibers into the caudal region of the cord is probably not involved in functional recovery. It is suggested that functional recovery is mediated by hindlimb proprioceptive afferents, which activate the lumbosacral motor central pattern generator.
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PMID:Recovery of function in spinalized, neonatal rats. 193 20

Systemic injections of GM1 gangliosides can enhance behavioral recovery from brain damage as measured by a number of cognitive tasks. The functional recovery is not due to GM1-induced alterations in activity, emotional arousal, or heightened sensitivity to mild, noxious stimulation. In addition, the recovery endures long after all treatments are terminated. Although the specific actions by which GM1 treatments facilitate recovery are unknown, evidence does suggest that both anomalous sprouting and protection of neurons from secondary consequences of injury may be involved in the repair process.
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PMID:Some functional consequences of chronic GM1 ganglioside administration in brain damaged rats. 213 Jun 58

Increasing evidence is available indicating that systemically administered GM1 is able to provide for functional recovery in different experimental models of CNS injury, including cerebral ischemia. Current evidence indicates that the GM1 effects are associated, in the acute phase, with attenuation of secondary neuronal damage due to its capability to antagonize excitatory amino acid-related neurotoxicity in vivo as in vitro. Furthermore, the ganglioside is able to facilitate occurrence of long-term reparative processes, an effect most likely reflecting the potentiation of the action of neuronotrophic factors. This bifaceted action of GM1 makes the ganglioside ideally suited for clinical treatment of patients afflicted by cerebrovascular insufficiencies.
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PMID:Monosialoganglioside effects following cerebral ischemia: relationship with anti-neuronotoxic and pro-neuronotrophic effects. 213 Jun 63

In vitro studies have shown that monosialoganglioside GM1 reduces excitatory amino acid-related neurotoxicity by limiting the downstream consequences of abusive excitatory amino acid receptor stimulation. Systemic administration of GM1 appears to be efficacious in reducing acute neuronal damage and in facilitating medium- and long-term functional recovery after brain injury. We propose that GM1 protective effects in the acute injury phase results from attenuation of excitotoxicity, whereas the functional recovery seen at longer term could reflect GM1 potentiation of neuronotrophic factors. The potential therapeutic efficacy of GM1 administration in humans is suggested by clinical studies demonstrating improved neurologic outcome in stroke patients.
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PMID:Hypoxic-ischemic damage and the neuroprotective effects of GM1 ganglioside. 223 92

Gangliosides are normal constituents of the plasma membrane. Exogenous gangliosides can be incorporated into the membrane and extensive research in nervous tissue has demonstrated a beneficial effect of gangliosides on the functional recovery of lesioned neurons and protection against neurotoxins. This paper shows that the effect of gangliosides is not restricted to neurons. The monosialoganglioside GM1 efficiently increases the survival of thymocytes and protects them against both the lytic effect of the glucocorticoid prednisolone and the effect of a thymocytotoxic serum. The protective effect of GM1 was achieved both in vitro and in vivo.
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PMID:Monosialoganglioside GM1 increases survival of thymocytes. 278 24

GM1 ganglioside injections (i.p.) reduce amphetamine-induced asymmetric rotation in rats 48 h after a partial unilateral transection of the nigrostriatal pathway. We found that this reduction was maximal when rats received their first GM1 injection within 2 h after surgery. Rats injected 4-12 h after surgery, or rats only pretreated with GM1, showed no significant effect on rotation. Striatal membrane Na+,K+-ATPase in rats injected with GM1 0-2 h after hemitransection showed only a 10% loss in activity (versus the untransected hemisphere) as compared to control losses of 38%. The maintenance of membrane Na+,K+-ATPase activity in GM1-treated rats may be one mechanism by which a balance between hemispheres in striatal dopaminergic transmission is preserved, resulting in reduced asymmetric rotation. The observation that there is a critical postsurgical period when GM1 administration results in optimal functional recovery supports our hypothesis that gangliosides are exerting an acute effect on damaged CNS tissue. This acute effect is further evidenced by the reduced loss of membrane Na+,K+-ATPase following injury.
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PMID:Acute effects of GM1 ganglioside: reduction in both behavioral asymmetry and loss of Na+, K+-ATPase after nigrostriatal transection. 301 50

As evidenced by their ability to reduce cerebral edema, exogenous ganglioside administration exerts acute effects on CNS injury processes. We report here that ganglioside (GM1 or AGF2) treatment results in a 52% decrease in mortality 48 hours after the induction of ischemia in gerbils by permanent unilateral ligation of the common carotid artery. By comparing the occluded vs. nonoccluded sides of the brain (cortex and hippocampus) we found a significant loss of membrane Na, K-ATPase activity due to ischemia in control animals, but no such differences were found between the hemispheres of ganglioside-treated gerbils. We hypothesize that gangliosides may be "protecting" membrane function as indicated by these ATPase analyses, reducing local CNS damage at the time of injury (i.e., reduced cell loss, fiber degeneration, membrane failure). By acutely limiting the extent of CNS tissue damage, conditions may be optimized for any subsequent CNS regrowth and functional recovery.
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PMID:Gangliosides (GM1 and AGF2) reduce mortality due to ischemia: protection of membrane function. 302 26


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