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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Excitatory dicarboxylic amino acid neurotransmitters, particularly glutamate, have been implicated in mediating neuronal cell injury in brain ischemia-anoxia, epilepsy, and stroke. Glutamate neurotoxicity has been demonstrated in several in vitro models, as well as its prevention by a variety of agents, including several sialic acid-containing glycosphingolipid species, gangliosides. We have now examined ganglioside effects in anoxic exposed cultures of granule cells from Postnatal Day 8 rat cerebellum. Cells between 10 and 12 days in vitro were placed into an anoxic atmosphere or subjected to a chemical model of anoxia by a pulse exposure to rotenone. Widespread neuronal degeneration of neuronal cell bodies and their associated neurite network was seen the following day. These effects on cell vitality at the morphological level were quantitatively confirmed by measuring the photometric reduction of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide to a blue formazan product. This neuronal injury was abolished by the specific N-methyl-D-aspartate receptor noncompetitive antagonists Mg2+, phencyclidine and MK-801, suggesting that this subtype of glutamate receptor is involved in the pathogenesis of anoxic granule cell injury. Pretreatment for 30 to 60 min or more or concurrent treatment with ganglioside GM1 largely prevented the ensuing neuronal death (ED50 = 25 microM), even 4 days later. Degeneration induced by exogenous glutamate was equally reduced. Asialo GM1 (lacking sialic acid) was ineffective. These results are consistent with the observed beneficial effects of the gangliosides in ischemic brain injury models in vivo.
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PMID:Monosialoganglioside GM1 protects against anoxia-induced neuronal death in vitro. 268 18

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

The effect of the ganglioside GM1 on amplitude of the electroencephalogram, neurologic function, and histology has been studied in chronic middle cerebral artery occlusion in cats. Ischemia was produced by a 2-hour occlusion of the left middle cerebral artery and was followed by a 7-day observation period. GM1 was intravenously administered 30 minutes after occlusion and daily during the observation period. Using the reduction in the electroencephalogram amplitude to measure stroke severity, three cats with mild, three cats with moderate, and three cats with severe stroke were treated with 5 mg/kg GM1. Nine cats, three in each group, were treated with 30 mg/kg GM1, while nine cats, three in each group, received middle cerebral artery occlusion but no treatment. In all cats there was a precipitous fall in mean electroencephalogram amplitude during occlusion, followed by a secondary fall during the observation period. Treated cats showed better recovery of electroencephalogram amplitude during the first 4 hours of reperfusion and a smaller secondary fall than untreated cats. Treated cats, especially those treated with 5 mg/kg GM1, showed significant recovery of neurologic deficits compared with untreated cats. Histologic damage was less in treated cats than in untreated cats. Some cats treated with 30 mg/kg GM1 exhibited convulsions, whereas no untreated cat showed any seizure activity. Our findings suggest that gangliosides may improve the recovery of both neurologic deficits and morphologic damage in the central nervous system. These positive effects might be tentatively explained by stimulation of enzymatic activities such as Na+, K+-ATPase and adenyl cyclase.
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PMID:Effect of the ganglioside GM1 on neurologic function, electroencephalogram amplitude, and histology in chronic middle cerebral artery occlusion in cats. 340 Jan 1

The effect of the ganglioside GM1 on the recovery of local cerebral glucose metabolism (lCMRgl), recovery kinetics of cerebrocortical electrical activity, cerebral blood flow and redox state as well as histological changes following focal ischemia has been studied in the cat. Ischemia was produced by occlusion of the left middle cerebral artery (MCA), and GM1 (30 mg/kg) was injected intravenously at 30 min after the MCA occlusion or at the time of release of the occlusion, at 120 min. Another group of animals were subjected to the same ischemic insult, but without GM1 treatment, and sham-operated treated and not treated cats were also studied. The animals of both GM1-treated and non-treated stroke groups were classified into 2 groups (severe and moderate) depending on the depression of electrocortical activity in the ischemic hemisphere at 30 min of the ischemia. There was a significant increase in local cerebral blood flow in the ischemic area in the treated animals. Additionally there was a significant treatment effect on the left peripheral MCA territory for lCMRgl in the 30 min treated moderate group, (p less than .05). This group of animals showed decreased lCMRgl accompanied by less severe histological damage suggesting that GM1 may produce metabolic depression so as to maintain a normal flow-metabolism couple and prevent ischemic structural damage. The possible mechanism of metabolic depression induced by GM1 is briefly discussed.
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PMID:Effect of the ganglioside GM1, on cerebral metabolism, microcirculation, recovery kinetics of ECoG and histology, during the recovery period following focal ischemia in cats. 381 Jul 17

The lipid composition of rat spinal cord undergoing postmortem autolysis for 3 min and for 4 h at 38 degrees C was investigated as a model for lipid changes in total spinal cord ischemia. The only change in cords incubated for 3 min was an 11.7% decrease in cholesterol/g fresh weight. The cords incubated for 4 h showed a similar 11.6% decrease in cholesterol/g fresh weight as well as a 5.6% increase in water content and a 22% decrease in phosphatidyl serine. Changes of marginal statistical significance included a 15% increase in lipid phosphorus/g dry wt. and a 15% decrease in G4 (GM1)1 in the 4 h incubated cords. Therefore, autolytic processes are of little consequence in total spinal cord ischemia and attention should now be focused on exogenous pathogenetic factors to explain such ischemic changes in spinal cord. We also report discovery of an alkali-labile ganglioside, G1a in rat spinal cord.
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PMID:Effects of postmortem autolysis on the lipids of rat spinal cord. 611 47

In this study Mongolian gerbils were submitted to a normothermic bilateral carotid ligation lasting 5 min. A noncompetitive antagonist of NMDA receptors, MK-801, 0.8 mg/kg, was injected i.p. 30 min before ischemia, or the ganglioside GM1, 30 mg/kg, was given i.p. for 3 days, twice a day. The morphology of the hippocampal CA1 neurones and the brain content of cyclooxygenase metabolites of arachidonic acid: prostaglandin 6-keto PGF1 alpha and thromboxane Tx B2 were studied. Untreated ischemia induced the accumulation in brain of the 6-keto PGF1 alpha and Tx B2 immunoreactive materials, and resulted in a lesion of 70% of CA1 neurones. In the MK-801- and GM1-pretreated groups the postischemic levels of Tx B2 were significantly decreased. However MK-801 and GM1 did not prevent damage to the CA1 neurones in gerbils normothermic after ischemia, whereas a partial neuroprotection was observed in hypothermic, MK-801 treated gerbils. The results of this study indicate that NMDA receptors may participate in the mechanism of postischemic release of eicosanoids in brain. They also confirm a potential modulatory role of gangliosides. These results are discussed in terms of the involvement of cyclooxygenase metabolites of arachidonic acid in the mechanism of a selective delayed neuronal damage to the hippocampus CA1 after ischemia.
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PMID:Effects of MK-801 and ganglioside GM1 on postischemic prostanoid release and hippocampal lesion in gerbil brain. 788 81

This study aimed to investigate the effects of monosialoganglioside (GM1) when administered early in a model of cerebral focal ischemia, in the rabbit. The statistical evaluation of the electroencephalographic changes (quantified EEG analysis, QEEG) due to the ischemic event showed that the early treatment (1-3-24 h) with GM1 reduced the EEgraphic pattern typical of this model of cerebral ischemia. Considering the observation period, we hypothesized that it was due to the formation of an oedema of a lesser degree compared to the untreated group. Particularly, we did not obtain the increase in delta activity on the contralateral hemisphere, which we thought was expression of the diaschisi phenomenon.
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PMID:Early effects of GM1 in experimental cerebral focal ischemia in rabbits. 806 Jun

Using the quantitative autoradiographic [14C]2-deoxyglucose technique, regional cerebral metabolic rates for glucose (rCMRglc) were measured in awake male Fischer-344 rats at 1, 2, 3, 4 and 6 h after administration of GM1 30 mg/kg and at 3 h after GM1 150 or 300 mg/kg. GM1 is a natural compound that is able to prevent neuron degeneration induced by exposure to excitatory amino acids in vitro and by ischemia or neurotoxins in vivo. GM1 30 mg/kg, a dose very effective in preventing excitatory amino acid-induced neurotoxicity, produced minimal rCMRglc change over a 6 h period. GM1 150 and 300 mg/kg reduced rCMRglc, in 14 (31%) and in 29 (64%) brain regions, respectively. Maximal metabolic effects occurred in hippocampal areas which possess, in specific subfields, the highest brain concentrations of different excitatory amino acid receptor subtypes. This finding suggests an effect by GM1 on postreceptor mechanisms common to different excitatory amino acids.
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PMID:The monosialoganglioside GM1 dose-dependently reduces regional cerebral metabolic rates for glucose in awake rats. 810 15

Many reports indicate that GM1 ganglioside is effective in reducing CNS ischemic injury in animal models. These models employ invasive surgery to induce ischemic damage in otherwise healthy animals. The purpose of this study was to determine if the beneficial effects of GM1 could be generalized to Spontaneously Hypertensive Rats-Stroke Prone (SHRSP). The SHRSP strain develops a pathology similar to those observed in patients with stroke. The SHRSP have "risk" factors that include hypertension, fibrinoid necrosis, and sensitivity to diet. Female SHRSP were randomly assigned to GM1- or saline-treatment conditions. Rats were fed a stroke-inducing diet. Daily body weights, weekly blood pressure, time of stroke onset, and age at death were recorded. Spontaneous activity and performance on a tail-hang test were assessed thrice weekly. The results indicate that GM1 treatment did not delay the time of stroke onset or death. GM1 did reduce hyperactivity in the initial stages of the ischemic pathology, but did not prevent the marked decline in behavioral activity observed at later time points. There were no differences in weight loss, performance on the tail-hang test, or number of CNS injury-related symptoms observed. These findings suggest that GM1 was not as effective in decreasing mortality, weight loss, or behavioral deficits in SHRSP as previously reported using other animal models of ischemia. Distinguishing between those animal models in which GM1 is more and less effective may be useful in determining under which clinical situations GM1 is likely to be most suitable.
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PMID:GM1 ganglioside treatment of spontaneously hypertensive stroke prone rats. 815 30

The ability of brain preparations from 20-day-old rat fetuses to synthesize prostanoids in vitro before and after interruption of the maternal-fetal blood flow was examined using a radioimmunoassay technique. Synthesis of thromboxane B2 (TxB; the stable thromboxane A2 metabolite) decreased with increasing restriction time; conversely, it was elevated with reperfusion. Synthesis of 6-keto prostaglandin F1 alpha (PGF; the stable prostacyclin metabolite) and prostaglandin E2 (PGE) prostanoids remained unchanged after 20 min restriction and through a 2 hr reperfusion period. Intraperitoneal administration of GM1 (45 mg/kg) into the pregnant rat, 3 hr before restriction, stimulated synthesis of PGE and reduced synthesis of TxB. A prostanoid vasoactive index (PVI), which reflects the relative proportion of the three prostanoids synthesized and asserts the vasoactive potential of the brain tissue, was established. A rise in this value was attained after intrafetal administration into the peritoneal cavity of either GM1, GM3, or isopropyl-GM1 (AGF44) gangliosides, each given at 40 micrograms dose in 5 microliters volume, and N-dichloroacetyl-sphingosine (LIGA20; 15 micrograms/5 microliters) ganglioside analog, 1 hr before restriction. The effect was primarily due to an increase in the capacity of fetal brain tissue to synthesize PGE and, to a lesser extent PGF, vasodilating prostanoids. The N-methyl-D-aspartate (NMDA) receptor-blocker MK801 (6.6 micrograms/2 microliters) and the platelet activating factor (PAF) receptor antagonist BN52021 (0.1 mumol/2 microliters), given by the same route, effectively raised by 60-80% the vasodilating potential of the brain tissue following ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Gangliosides stimulate synthesis of prostaglandin E2 and prostacyclin in fetal rat brain hemispheres after episodes of global intrauterine ischemia. 827 17


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