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Query: UMLS:C0917798 (cerebral ischemia)
 17,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Changes in content of selected neuroactive amino acids [glutamic acid, aspartic acid, glycine, gamma-aminobutyric acid (GABA) and taurine] and acetylcholine (ACh) in the rat hippocampus following transient forebrain ischemia were investigated using male Wistar rats. Rats were allowed to survive for 1 or 5 days following 10 or 20 min of 4-vessel occlusion, and killed by a focused microwave irradiation. A significant reduction in all neuroactive amino acids examined except GABA was noted in the hippocampus on the fifth day. One day after the 4-vessel occlusion for 10 min, no significant effect on the content of neuroactive amino acids in all brain areas was observed. gamma-Aminobutyric acid content in the hippocampus was only significantly reduced on the fifth day after the occlusion for 20 min. Similarly, a significant decrease in ACh content in the hippocampus was observed on the fifth day after the occlusion for 20 min. Considering the data that a significant loss of neuronal cells in the hippocampus (delayed neuronal death) was detected only 5 days after the 4-vessel occlusion, it can be said that the alterations in the hippocampus of neuroactive amino acids such as glutamic acid, aspartic acid, glycine and taurine are more sensitive than those in GABA and ACh against cerebral ischemia. A possible correlation of these changes of neuroactive amino acids in the occurrence of delayed neuronal death in the hippocampus is also suggested.
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PMID:Changes in content of neuroactive amino acids and acetylcholine in the rat hippocampus following transient forebrain ischemia. 136 66

The protective effect of vinconate, a vinca alkaloid derivative, on ischemia-induced neuronal damage was investigated using a model of rat forebrain ischemia caused by occlusion of four vessels. Hippocampal cell loss was observed histologically and neurochemically 5 days after 10 min of ischemia. Treatment with vinconate (50 and 200 mg/kg i.p.) before cerebral ischemia significantly suppressed neuronal cell loss in the hippocampal CA1 region and the decrease in the content of neuroactive amino acids in the hippocampus. The release of neuroactive amino acids in the hippocampus was significantly increased by cerebral ischemia. Pretreatment with vinconate (50 and 200 mg/kg i.p.) significantly attenuated the increased release of glutamic acid and aspartic acid, but not the release of gamma-aminobutyric acid (GABA), taurine and glycine. This suppressive effect of vinconate was antagonized by scopolamine (10(-5) M). The addition of vinconate (10(-11)-10(-4) M) had no effect on the binding of [3H]MK-801. These results indicate that pretreatment with vinconate attenuates the ischemia-induced release of excitatory amino acids into the extracellular space of the hippocampus via the stimulation of presynaptic muscarinic acetylcholine receptors. The present results also suggest that this suppressive effect of vinconate on the release of excitatory amino acids (glutamic acid and aspartic acid) may play a crucial role in the protective action of this agent against ischemia-induced neuronal damage in the hippocampus.
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PMID:Protective effect of vinconate on ischemia-induced neuronal damage in the rat hippocampus. 146 4

A massive striatal dopamine release (241-fold increase) was observed in a previous study during acute cerebral ischemia in rats. In this study, extracellular levels of glutamic acid (GLU), gamma-aminobutyric acid (GABA) and lactic acid were simultaneously determined using in vivo brain dialysis in the striatum of spontaneously hypertensive rats during cerebral ischemia and after recirculation. Extracellular GABA levels increased to 932 +/- 75% (mean +/- SEM) of the resting level and GLU increased to 390 +/- 63% during 20 min ischemia. Although ischemia-induced release of GLU and GABA was demonstrated in this study, the degree of increase was smaller than that of dopamine. These findings may be relevant to the pathophysiology of cerebral ischemia in the striatum.
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PMID:Striatal glutamic acid and gamma-aminobutyric acid in transient cerebral ischemia in spontaneously hypertensive rats. 197 32

Male Wistar rats were subjected to 20 min of cerebral ischemia by means of 4-vessel occlusion. The topography of regional, selective neuron loss in this model corresponded to areas with pronounced glutamate high affinity uptake (presynaptic receptors), suggesting that transmitter glutamate is involved in the mechanism of neuron damage. One group of animals was injected with the glutamate antagonist, glutamic acid diethyl ester (GDEE) before ischemia. The regional neuron loss was rated using a semiquantitative scale. No statistically significant difference was found between the groups. The results do not exclude a possible role of transmitter glutamate in the pathogenesis of ischemic brain damage. More specific and potent glutamate antagonists are needed in order to clarify such a mechanism.
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PMID:Selective neuron loss after cerebral ischemia in the rat: possible role of transmitter glutamate. 714 96

The time course of changes in extracellular glutamic acid levels and their Ca2+ dependency were studied in the rat striatum during focal cerebral ischaemia, using microdialysis. Ischaemia-induced changes were compared with those produced by high K(+)-evoked local depolarization. To optimize time resolution, glutamate was analysed continuously as the dialysate emerged from the microdialysis probe by either enzyme fluorimetry or biosensor. The Ca2+ dependency of glutamate changes was examined by perfusing the probe with Ca(2+)-free medium. With normal artificial CSF, ischaemia produced a biphasic increase in extracellular glutamate, which started from the onset of ischaemia. During the first phase lasting approximately 10 min, dialysate glutamate level increased from 5.8 +/- 0.9 microM.min-1 to 35.8 +/- 6.2 microM where it stabilized for approximately 3 min. During the second phase dialysate glutamate increased progressively to its maximum (82 +/- 8 microM), reached after 55 min of ischaemia, where it remained for as long as it was recorded (3 h). The overall changes in extracellular glutamate were similar when Ca2+ was omitted from the perfusion medium, except that the first phase was no longer detectable and, early in ischaemia, extracellular glutamate increased at a significantly slower rate than in the control group (2.2 +/- 1 microM.min-1; p < 0.05). On the basis of these data, we propose that most of the glutamate released in the extracellular space in severe ischaemia is of metabolic origin, probably originating from both neurons and glia, and caused by altered glutamate uptake mechanisms.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Extracellular glutamate during focal cerebral ischaemia in rats: time course and calcium dependency. 791 20

We tested the effect of flupirtine against ischemic and excitotoxic neuronal damage as well as on the glutamate-induced rise in cytosolic calcium ion concentration (= [Ca2+]i). For in vivo experiments we used a model of focal cerebral ischemia in mice. The middle cerebral artery was permanently occluded and 48 h afterwards brain tissue was stained with neutral red, perfusion-fixed and the infarct surface was determined planimetrically. Pretreatment with flupirtine significantly reduced the infarct area (controls: 24.3 +/- 4.8 mm2, 1 mg/kg flupirtine: 20.1 +/- 3.6 mm2 and 10 mg/kg flupirtine: 19.5 +/- 3.9 mm2; P < 0.05), whereas postischemic application of flupirtine failed to reduce the infarct area. For in vitro studies, primary neuronal cultures were prepared from the hippocampi of newborn rats and excitotoxic damage was induced by exposing the cells to 500 mu M L-glutamate for 30 min. We could demonstrate that flupirtine (1-10 microM) was capable of protecting neurons against glutamate-induced cytotoxicity. In order to elucidate the underlying mechanism of action, we tested the effect of flupirtine on the glutamate-induced rise in [Ca2+]i using the Ca2+-indicator fura-2. L-Glutamate added in a final concentration of 100 microM to the cultured cells for 16 s caused a rise in [Ca2+]i from about 100 nM to 900 nM. Flupirtine (0.1-10 microM) reduced the glutamate-induced rise in [Ca2+]i concentration dependently.
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PMID:Flupirtine protects neurons against excitotoxic or ischemic damage and inhibits the increase in cytosolic Ca2+ concentration. 875 Jul 7

The excitotoxic hypothesis of neurodegeneration has stimulated much interest in the possibility of using compounds that will block excitotoxic processes to treat neurologic disorders. Riluzole is a neuroprotective drug that blocks glutamatergic neurotransmission in the CNS. Riluzole inhibits the release of glutamic acid from cultured neurons, from brain slices, and from corticostriatal neurons in vivo. It is thought these effects may be partly due to inactivation of voltage-dependent sodium channels on glutamatergic nerve terminals, as well as activation of a G-protein-dependent signal transduction process. Riluzole also blocks some of the postsynaptic effects of glutamic acid by noncompetitive blockade of N-methyl-D-aspartate (NMDA) receptors. In vivo, riluzole has neuroprotective, anticonvulsant, and sedative properties. In a rodent model of transient global cerebral ischemia, a complete suppression of the ischemia-evoked surge in glutamic acid release has been observed. In vitro, riluzole protects cultured neurons from anoxic damage, from the toxic effects of glutamic-acid-uptake inhibitors, and from the toxic factor in the CSF of patients with amyotrophic lateral sclerosis.
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PMID:The pharmacology and mechanism of action of riluzole. 895 95

The extracellular glutamate concentration ([glu](o)) rises during cerebral ischemia, reaching levels capable of inducing delayed neuronal death. The mechanisms underlying this glutamate accumulation remain controversial. We used N-methyl-D-aspartate receptors on CA3 pyramidal neurons as a real-time, on-site, glutamate sensor to identify the source of glutamate release in an in vitro model of ischemia. Using glutamate and L-trans-pyrrolidine-2,4-dicarboxylic acid (tPDC) as substrates and DL-threo-beta-benzyloxyaspartate (TBOA) as an inhibitor of glutamate transporters, we demonstrate that energy deprivation decreases net glutamate uptake within 2-3 min and later promotes reverse glutamate transport. This process accounts for up to 50% of the glutamate accumulation during energy deprivation. Enhanced action potential-independent vesicular release also contributes to the increase in [glu](o), by approximately 50%, but only once glutamate uptake is inhibited. These results indicate that a significant rise in [glu](o) already occurs during the first minutes of energy deprivation and is the consequence of reduced uptake and increased vesicular and nonvesicular release of glutamate.
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PMID:Acute decrease in net glutamate uptake during energy deprivation. 1080 15

Glutamic acid, an excitatory amino acid, has been proposed to play a major deleterious influence in cerebral ischemia. However, the neuroprotective activity of various glutamate receptor antagonists is often low or absent, according to the animal model used. In the present study, we examined the effect of several antagonists acting on glutamate receptors of the N-methyl-D-aspartate (NMDA) type in rats submitted to a brief (5 minutes) global cerebral ischemia. The different compounds used were poorly active or inactive on behavioural and histologic alterations induced by ischemia. Our results suggest that, in this model, overactivation of NMDA receptor complex does not play a predominant role in the pathogenesis of ischemic brain damage.
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PMID:[Inefficacy of N-methyl-D-aspartate receptor complex antagonists on behavioral and histologic consequences of global cerebral ischemia in rats]. 1091 75

Major interest is currently focused on the development and evaluation of effective strategies for the pharmacological therapy of human stroke and cerebral ischemia, as well as some neurodegenerative disorders in which increased production of free oxygen radicals and the neurotoxic effect of excitatory amino acids may take place. Selected N-methyl-D-aspartate (NMDA) antagonists and antioxidants in the model of experimental oxidative stress induced by hypoxia and reoxygenation in rat hippocampal slices were tested. The putative antiglutamatergic effect of the antioxidant stobadine and its neuroprotective effect during oxidative stress was studied. NMDA antaonists 2-amino-5-phosphonovaleric acid (APV) and Mg2+, as well as the antioxidants stobadine and trolox, prevented the decrease of NMDA binding site number induced by hypoxia/reoxygenation in rat hippocampal slices. Moreover, stobadine, APV and Mg2+ prevented the decrease of NMDA binding site number due to glutamic acid incubation. Stobadine does not inhibit [3H]-glutamate binding and therefore does not seem to interact directly with glutamate binding sites. Thus, its neuroprotective effect in rat hippocampus exposed to hypoxia/reoxygenation does not seem to be based on a direct antiglutamatergic effect. The protective action of stobadine against the decrease of NMDA binding site number elicited by hypoxia/reoxygenation in rat hippocampus could rather be due to its antioxidant and antiradical effect.
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PMID:Effect of antioxidants and NMDA antagonists on the density of NMDA binding sites in rat hippocampal slices exposed to hypoxia/reoxygenation. 1269 Jul 2


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