g(m1)-ganglioside and Stroke

Ganglioside GM1 is a member of the ganglioside family which has been used in many countries and is thought of as a promising alternative treatment for preventing several neurological diseases, including cerebral ischemic injury. The therapeutic effects of GM1 have been proved both in neonates and in adults following ischemic brain damage; however, its clinical efficacy in patients with ischemic stroke is still uncertain. This review examines the recent knowledge of the neuroprotective properties of GM1 in ischemic stroke, collected in the past two decades. We conclude that GM1 may have potential for stroke treatment, although we need to be cautious in respect of its complications.

Topics: Animals; Brain Ischemia; Clinical Trials as Topic; G(M1) Ganglioside; Humans; Neuroprotective Agents; Stroke

In this mini-review I summarize our research efforts in ascertaining the possible neuro-reparative properties of the GM1 ganglioside and its cooperative effects with NGF in stroke-lesion models. We also review aspects of our NGF investigations which have recently led to the discovery that NGF is released in an activity-dependent manner in the form of its precursor molecule, proNGF. These studies support the notion that in the CNS NGF metabolism conversion and degradation occur in the extracellular milieu. We have also validated this pathway in vivo demonstrating that the pharmacological inhibition of the pro-to mature NGF conversion results in the brain accumulation of proNGF and loss and atrophy of cortical cholinergic synapses. Furthermore, we have gathered neurochemical evidence for a compromise of this newly discovered NGF metabolic pathway in Alzheimer's disease, explaining the vulnerability of NGF-dependent forebrain cholinergic neurons in this disease despite normal NGF synthesis and abundance of NGF precursor.

Topics: Aging; Animals; Atrophy; Brain; Cholinergic Neurons; G(M1) Ganglioside; Humans; Matrix Metalloproteinase 9; Nerve Growth Factor; Protein Precursors; Stroke; Tissue Plasminogen Activator

Gangliosides may have a protective effect on the central and peripheral nervous systems.. The objective of this review was to assess the effect of exogenous gangliosides in acute ischaemic stroke.. We searched the Cochrane Stroke Group trials register (last searched: May 2001) and contacted drug companies and main investigators of included trials.. Randomised trials of gangliosides compared with placebo or standard treatment in people with definite or presumed ischaemic stroke. Trials were included if people were randomised within 15 days of symptom onset and if mortality data were available.. One reviewer applied the inclusion criteria. Two reviewers independently extracted the data. Trial quality was assessed.. Twelve trials involving 2265 people were included. All the trials tested purified monosialoganglioside GM1. Only three trials described the randomisation procedure. Follow-up was between 15 to 180 days. Death at the end of follow-up showed no significant difference (odds ratio 0.91, 95% confidence interval 0.73 to 1.13). There was no difference shown between early (within 48 hours) and delayed treatment. For disability, three trials did not show any improvement in Barthel index score with gangliosides (weighted mean difference 2.1; 95% confidence interval -4.8 to 8.9). In two trials, eight patients experienced adverse effects that led to discontinuation of ganglioside treatment, seven had skin reactions and one developed Guillain-Barré syndrome.. There is not enough evidence to conclude that gangliosides are beneficial in acute stroke. Caution is warranted because of reports of sporadic cases of Guillain-Barré syndrome after ganglioside therapy.

Topics: Acute Disease; Brain Ischemia; G(M1) Ganglioside; Gangliosides; Humans; Stroke

Gangliosides may have a protective effect on the central and peripheral nervous systems.. The objective of this review was to assess the effect of exogenous gangliosides in acute ischaemic stroke.. We searched the Cochrane Stroke Group trials register (last searched: March 1999) and contacted drug companies.. Randomised trials of gangliosides compared with placebo or standard treatment in people with definite or presumed ischaemic stroke. Trials were included if people were randomised within 15 days of symptom onset and if mortality data were available.. One reviewer applied the inclusion criteria. Two reviewers independently extracted the data. Trial quality was assessed.. Eleven trials involving 2257 people were included. All the trials tested purified monosialoganglioside GM1. Only three trials described the randomisation procedure. Follow-up was between 15 to 180 days. Death at the end of follow-up showed no significant difference (odds ratio 0.91, 95% confidence interval 0.73 to 1.14). There was no difference shown between early (within 48 hours) and delayed treatment. For disability, two trials showed an improved Barthel index score with gangliosides (weighted mean difference 8.6, 95% confidence interval 1.2 to 16.0). In two trials, eight patients experienced adverse effects that led to discontinuation of ganglioside treatment, seven had skin reactions and one developed Guillain-Barré syndrome.. There is not enough evidence to conclude that gangliosides are beneficial in acute stroke. Caution is warranted because of reports of sporadic cases of Guillain-Barré syndrome after ganglioside therapy.

Topics: Brain Ischemia; G(M1) Ganglioside; Gangliosides; Humans; Stroke

Ganglioside GM1, which is particularly abundant in the central nervous system (CNS), is closely associated with the protection against several CNS disorders. However, controversial findings have been reported on the role of GM1 following ischemic stroke. In the present study, using a rat middle cerebral artery occlusion (MCAO) model, we investigated whether GM1 can protect against ischemic brain injury and whether it targets the autophagy pathway. GM1 was delivered to Sprague-Dawley male rats at 3 doses (25 mg/kg, 50 mg/kg, 100 mg/kg) by intraperitoneal injection soon after reperfusion and then once daily for 2 days. The same volume of saline was given as a control. Tat-Beclin-1, a specific autophagy inducer, was administered by intraperitoneal injection at 24 and 48 hours post-MCAO. Infarction volume, mortality and neurological function were assessed at 72 hours after ischemic insult. Immunofluorescence and Western blotting were performed to determine the expression of autophagy-related proteins P62, LC3 and Beclin-1 in the penumbra area. No significant changes in mortality and physiological variables (heart rate, blood glucose levels and arterial blood gases) were observed between the different groups. However, MCAO resulted in enhanced conversion of LC3-I into LC3-II, P62 degradation, high levels of Beclin-1, a large area infarction (26.3±3.6%) and serious neurobehavioral deficits. GM1 (50 mg/kg) treatment significantly reduced the autophagy activation, neurobehavioral dysfunctions, and infarction volume (from 26.3% to 19.5%) without causing significant adverse side effects. However, this biological function could be abolished by Tat-Beclin-1.. GM1 demonstrated safe and robust neuroprotective effects that are associated with the inhibition of autophagy following experimental stroke.

Topics: Animals; Apoptosis Regulatory Proteins; Autophagy; Beclin-1; Brain; Brain Ischemia; Disease Models, Animal; Drug Administration Schedule; G(M1) Ganglioside; Gene Expression Regulation; Gene Products, tat; Heat-Shock Proteins; Infarction, Middle Cerebral Artery; Injections, Intraperitoneal; Male; Microtubule-Associated Proteins; Neuroprotective Agents; Rats; Rats, Sprague-Dawley; Recombinant Fusion Proteins; Sequestosome-1 Protein; Signal Transduction; Stroke; Survival Analysis

Cytidine-5'-diphosphocholine (CDP-choline, Citicoline, Somazina) is in clinical use (intravenous administration) for stroke treatment in Europe and Japan, while USA phase III stroke clinical trials (oral administration) were disappointing. Others showed that CDP-choline liposomes significantly increased brain uptake over the free drug in cerebral ischemia models. Liposomes were formulated as DPPC, DPPS, cholesterol, GM(1) ganglioside; 7/4/7/1.57 molar ratio or 35.8/20.4/35.8/8.0 mol%. GM(1) ganglioside confers long-circulating properties to the liposomes by suppressing phagocytosis. CDP-choline liposomes deliver the agent intact to the brain, circumventing the rate-limiting, cytidine triphosphate:phosphocholine cytidylyltransferase in phosphatidylcholine synthesis. Our data show that CDP-choline liposomes significantly ( P < 0.01) decreased cerebral infarction (by 62%) compared to the equivalent dose of free CDP-choline (by 26%) after 1 h focal cerebral ischemia and 24 h reperfusion in spontaneously hypertensive rats. Beneficial effects of CDP-choline liposomes in stroke may derive from a synergistic effect between the phospholipid components of the liposomes and the encapsulated CDP-choline.

Topics: Animals; Brain; Brain Infarction; Brain Ischemia; Cholesterol; Choline; Cytidine Diphosphate Choline; Disease Models, Animal; Drug Combinations; Drug Synergism; G(M1) Ganglioside; Liposomes; Male; Phagocytosis; Phosphatidylcholines; Rats; Rats, Inbred SHR; Reperfusion Injury; Stroke; Treatment Outcome

Topics: Acute Disease; Animals; Antiparkinson Agents; Brain Ischemia; Drugs, Investigational; G(M1) Ganglioside; Humans; Neuroprotective Agents; Parkinson Disease; Stroke