Acute Effects of Gangliosides on CNS Injury

Karpiak, Stephen E.; Li, Yu Shu; Aceto, Paul; Mahadik, Sahebarao P.

doi:10.1007/978-1-4757-5309-7_32

Cited by 16 publications

(9 citation statements)

References 20 publications

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“…21]. The neuron-protecting effect of GMl in such situa tions has also been largely demonstrated [22][23][24][25][26][27][28][29][30][31][32], Our observations, although obtained in a relatively small sample of subjects, seem to confirm a correlation between the acute effect of the drug both in reducing experimental brain edema and in antagonizing excitatory amino acid neurotoxicity, and a positive clinical result. Our data can reasonably support the hypothesis of a new therapeutical approach with GMl to cerebral ischemia, also taking into account the good level of tolerability and safety demonstrated so far by the drug.…”

Section: Discussionsupporting

confidence: 70%

GM1 Ganglioside Therapy in Acute Ischemic Stroke

et al. 1992

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A double-blind, randomized, placebo-controlled clinical trial, involving two Italian centers, was carried out to evaluate the efficacy and safety of the monosialoganglioside GM1 in acute ischemic stroke. A total of 112 consecutive patients were recruited. The treatment (GM1 or placebo) was intravenously administered for 3 weeks and the follow-up lasted for 6 months. Semiquantitative clinical evaluations were performed on admission at the end of treatment (day 21) and at the end of follow-up (day 180), by using the Frithz-Werner Scale for the neurological recovery and the Barthel Index for the activities of daily living. On day 21, the statistical analysis showed a significant neurological improvement (p < 0.01) in the Frithz-Werner Scale in favor of the GM1 group. On day 180, the difference between the two groups was not significant for the Frithz-Werner Scale, while it reached significance for the activities of daily living (Barthel Index) in favor of the GM1-treated group (p < 0.05).

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Section: Discussionsupporting

confidence: 70%

GM1 Ganglioside Therapy in Acute Ischemic Stroke

et al. 1992

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“…9 Similar effects may underlie the decreased hypoperfusion and limitation of the CVR increase we observed in AGF 2-treated monkeys. In cats with transitory focal ischemia, a single dose of GM 1 increases CBF in the ischemic area, and GM 1 depresses local CMRGlu in the peripheral middle cerebral artery territory, in which the morphologic damage is less severe in treated cats.…”

Section: Discussionmentioning

confidence: 64%

Influence of monosialoganglioside inner ester on neurologic recovery after global cerebral ischemia in monkeys.

Cahn¹,

Borzeix²,

Aldinio³

et al. 1989

Stroke

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We assessed the consequences of transitory global cerebral ischemia and the influence of monosialoganglioside inner ester (AGF 2) treatment on neurologic outcome, cerebral blood flow, and cerebral metabolic rate in monkeys over 48 hours. Global cerebral ischemia was produced by a cervical tourniquet and a lowering of blood pressure to 6.65 kPa; recirculation followed after 30 minutes. AGF 2 (30 mg/kg) was administered intravenously immediately after initiation of recirculation and intramuscularly twice a day for 48 hours. Our results show that treatment with AGF 2 significantly accelerated the rate of neurologic recovery. Improvement was evident 5 hours after ischemia; full neurologic recovery was observed in half of the monkeys 48 hours after ischemia. This recovery was associated with a less severe reduction in cerebral blood flow without a concomitant increase in the cerebral metabolic rate. (Stroke 1989; 20:652-656) G angliosides are sialic acid-containing glycosphingolipids with particular abundance in the outer membrane surface of neuronal cells.' Although their biologic function is still largely obscure, considerable evidence now indicates that systemically administered gangliosides are effective in improving the outcome following neuronal injury to adult rodents. In the initial work of Ceccarelli et al, 2 a mixture of bovine brain gangliosides enhanced recovery of the denervated cat nictitating membrane, an effect most probably associated with an enhanced rate of axonal regrowth.3 Subsequently, the monosialoganglioside GM 1 (nomenclature according to Svennerholm 4 ) alone was found to affect recovery following injury to the central nervous system (CNS). For example, following partial unilateral hemitransection of the nigrostriatal pathway, chronically administered GM 1 facilitated the recovery of dopaminergic synaptic function in the lesioned striatum.5 This effect was associated with both enhanced survival of nigral dopaminergic cell bodies and with the associated reduction of the imbalance in energy metabolism and blood flow between the striata of the lesioned and unlesioned sides. Received March 4, 1988; accepted October 18, 1988. GM 1 effects have also been detected during the acute phase following brain insults, including cerebral ischemia. GM 1 treatment has been shown to have beneficial effects following both transitory middle cerebral artery occlusion in cats and permanent unilateral ligation of the common carotid artery in gerbils. -9We describe the effects of AGF 2, the inner ester derivative of GM 1, following transitory global cerebral ischemia in monkeys. We used AGF 2 because of its reportedly greater ability to penetrate the blood-brain barrier. 10 Materials and MethodsWe used 27 cynomolgus monkeys {Macaca fascicularis) of either sex weighing 3-6 kg. Anesthesia was induced with 3 mg/kg i.m. ketamine hydrochloride followed by an intravenous perfusion of 25 mg/kg chloralose. The monkeys were intubated and then ventilated (Delhomme, Bird Mark 8, Paris, France) so as to maintain Pacc>2 at 5...

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“…G M i ganglioside treatment reducing mortality after brain injury has also been reported in rats, 23 indicating that gangliosides can reduce impairment in the acute phase following a CNS insult. 12 If functional deficits can be minimized in the short term, the possibility for facilitated recovery in the long term should be maximized.…”

Section: Resultsmentioning

confidence: 99%

“…Preliminary studies indicate that this internal ester of G MI , AGF2, activates Na, K-ATPase activity more than G M1 . 12 The fact that the overall levels of Na, K-ATPase activity are lower in the ganglioside-treated gerbils vs. saline-injected controls may result from two factors. First, approximately one-third of the gerbils assayed for ATPase activity in the ganglioside groups are animals that were predicted to have died from the ischemia.…”

Section: Resultsmentioning

confidence: 99%

Gangliosides (GM1 and AGF2) reduce mortality due to ischemia: protection of membrane function.

Karpiak¹,

Li²,

Mahadik³

1987

Stroke

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As evidenced by their ability to reduce cerebral edema, exogenous ganglioside administration exerts acute effects on CNS injury processes. We report here that ganglioside (GMI 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 «niipals, 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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Acute Effects of Gangliosides on CNS Injury

Cited by 16 publications

References 20 publications

GM1 Ganglioside Therapy in Acute Ischemic Stroke

GM1 Ganglioside Therapy in Acute Ischemic Stroke

Influence of monosialoganglioside inner ester on neurologic recovery after global cerebral ischemia in monkeys.

Gangliosides (GM1 and AGF2) reduce mortality due to ischemia: protection of membrane function.

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