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

Repetitive cerebral ischemia in gerbils produces delayed neuronal damage in the substantia nigra reticulata (SNr). This damage begins 4 to 5 days after the insult and is severe by day 7. The damage can be attenuated by GABA agonists. There is a prominent GABAergic striatal pathway to the SNr. Damage to this pathway leads to progressive loss of SNr neurons. This loss can be prevented by GABA agonists. We postulate that, ischemia-induced lack of GABAergic inhibitory input from the striatum to the SNr, may be responsible for this delayed neuronal damage. In the present experiment, we have measured striatal extracellular GABA concentrations with or without nipecotic acid, a GABA-reuptake inhibitor, in gerbils exposed to repetitive ischemia. GABA levels were measured on days 1, 3, 5, and 7 after the ischemic insult. Five control animals and a similar number of ischemic animals were monitored on each day. Extracellular fluid was collected using in vivo microdialysis and GABA levels were measured by electrochemical detection with HPLC. The extracellular striatal GABA levels were very low in the initial three specimens collected, both in the control and in the ischemic animals. However, addition of nipecotic acid resulted in an immediate increase of GABA in measurable range. In comparison to the controls, the increase in GABA on day 1 and 3 were significantly higher in animals with repetitive ischemia (two-way ANOVA with repeated measures). Subsequent measurements showed a gradual decrease in GABA levels when compared to controls. The increase in GABA with nipecotic acid was significantly lower on day 7 after the ischemic insults when compared to the controls. The increased GABA responsiveness immediately after the ischemic insults may reflect a protective effect against excitotoxicity. The subsequent decline in GABA levels after the insult may be secondary to progressive loss of striatal GABAergic neurons. This may contribute to the production of delayed neural damage in the SNr by a decrease in the inhibitory striatal input.
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PMID:Progressive decrease in extracellular GABA concentrations in the post-ischemic period in the striatum: a microdialysis study. 788 74

Release of the excitotoxic amino acids, glutamate and aspartate, from the ischemic rat cerebral cortex was compared in two models; the seven vessel occlusion model (7VO) of complete cerebral ischemia and the four vessel occlusion model (4VO) of incomplete cerebral ischemia. Amino acid efflux into cortical superfusates was measured using cortical cups placed on both hemispheres. Whereas a 20 min period of ischemia causes a pronounced release of glutamate and aspartate from the 4VO model, efflux was significantly reduced in the 7VO model. Release of the inhibitory transmitter GABA, was similar in the two models. This result suggests that excitotoxic amino acid efflux into the extracellular spaces of the cerebral cortex may be enhanced by the residual blood flow in an incomplete ischemia.
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PMID:Transmitter amino acid release from rat neocortex: complete versus incomplete ischemia models. 789 7

This review describes the neuropathology and pathophysiology of interneurons in dorsal hippocampus of the adult rat subjected to transient global cerebral ischemia. The object is to verify if the interneurons die or survive after an ischemic insult, and study if ischemia changes GABA inhibition in the period preceding delayed CA1 pyramidal cell death. The findings are discussed from the point of the hypothesis that loss of GABA inhibition may result in excitatory hyperactivity (possibly epilepsy) and excitotoxic glutamate release. Thereby, early ischemic damage to interneurons may exacerbate the ischemic process resulting in the major and delayed CA1 cell death in hippocampus. Interneurons, located in dentate hilus, and a small number of interneurons located in the mossy fiber layer are selectively lost after ischemia. These interneurons contain somatostatin and neuropeptide Y, but the inhibitory or excitatory nature of them is unknown. However, counts of all hippocampal cells immunoreactive for glutamic acid decarboxylase showed that the GABA interneurons survive ischemia. It is therefore suggested that the vulnerable interneurons in hilus and the mossy fiber layer do not contain GABA. As the GABA interneurons, other hippocampal interneurons also survive ischemia. Among these, the CA1 and CA3 interneurons containing neuropeptide Y demonstrate permanently reduced immunoreactivity for neuropeptide Y, evident 1-2 days after ischemia. Another subpopulation transiently shows a decrease in immunoreactivity for parvalbumin approximately 4 days after ischemia. These results are in contrast to the finding that protein synthesis in hippocampal interneurons returns to preischemic levels 9 hours after ischemia. The integrity between excitation and inhibition in CA1 is unchanged in hippocampal slices taken from animals 1-2 days after ischemia. Furthermore, GABA can readily be released upon potassium stimulation in the period preceding CA1 pyramidal cell death. Binding to hippocampal benzodiazepine sites, however, declines prior to ischemic CA1 pyramidal cell death. It is demonstrated that administration of diazepam and GABA uptake inhibitors during this period offers postischemic neuron protection in CA1. There is no conclusive evidence of excitatory hyperactivity preceding ischemic CA1 pyramidal cell death. On the contrary, results from Chang et al. (1) suggest that ischemic loss of interneurons in the dentate hilus is associated with an increase in inhibition. However, it is suggested that GABA inhibition is insufficient to counterbalance the detrimental process during normal or even reduced postischemic excitation, since drugs believed to increase GABA inhibition reduce ischemic cell death. The early and permanent reduction in neuropeptide Y immunoreactivity may reflect a reduced capacity of these interneurons to release neuropeptide Y and thereby reduce presynaptic glutamate release.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Interneurons in rat hippocampus after cerebral ischemia. Morphometric, functional, and therapeutic investigations. 790 56

The redistribution of glutamate and GABA in postischemic brains was examined immunocytochemically using the gerbil model of unilateral 1 h cerebral ischemia. In the cerebral neocortex, the majority of neurons underwent recovery processes after 5 h of recirculation, while neurons in the hippocampus were irreversibly damaged. Glutamate-like immunoreactivity (LI) was highly increased in the degenerating hippocampal CA3 pyramidal cells after recirculation, while in the neocortex and the hippocampal CA1 sector, the pyramidal cells showed only slightly increased glutamate-LI. GABA-LI-positive punctae in the neuropil, corresponding to neuronal processes of GABAergic neurons, were accentuated after recirculation both in the cerebral neocortex and the hippocampus. Although the astrocytes on the nonischemic side showed neither glutamate-LI nor GABA-LI, the swollen astrocytes and their foot processes, which were observed after recirculation, often showed strong glutamate-LI and GABA-LI. These data suggest (1) the accumulation of glutamate or glutamate-like substances, especially in the CA3 pyramidal cells, (2) the excitation of the GABAergic neurons and their subsequent uptake of GABA, and (3) the sequestration of the extracellular neurotransmitters by astrocytes in the postischemic period.
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PMID:Redistribution of glutamate and GABA in the cerebral neocortex and hippocampus of the Mongolian gerbil after transient ischemia. An immunocytochemical study. 791 66

The effects of indomethacin (10 mg/kg) on the release of the transmitter amino acids, glutamate, aspartate, GABA, and of the purines, adenosine and inosine, from the cerebral cortex was studied in a four-vessel occlusion rat model of cerebral ischemia/reperfusion. In comparison with the control group, indomethacin significantly attenuated the ischemia-evoked release of glutamate and aspartate, but not of GABA. Adenosine levels in the cortical superfusates were significantly elevated following indomethacin administration. As indomethacin is a potent inhibitor of adenosine uptake, these results suggest that, by blocking adenosine uptake, indomethacin could elevate extracellular adenosine levels and depress glutamate and aspartate efflux as a consequence of the activation of adenosine A1 receptors.
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PMID:Indomethacin modulates ischemia-evoked release of glutamate and adenosine from the rat cerebral cortex. 795 50

GABA-immunoreactivity in the thalamic reticular nucleus was studied in rats subjected to 10 min global cerebral ischemia, due to experimentally induced cardiac arrest. The studies were performed in different postischemic periods (10 min, 1 h and 24 h after ischemia) with postembedding immuno-gold technique for electron microscopy, applying antisera raised against protein-gamma amino butyric acid-conjugates. Transient reduction of gold particles content, indicating GABA appearance and distribution in neuronal perikarya and synaptic terminals, was noticed 10 min and 1 h after ischemia. Reduction of immunoreactivity accompanied ultrastructural abnormalities involving both neurons and synapses and taking the form of severe swelling and disorganization of organelles arrangement. Immunocytochemical abnormalities concerning neuronal perikarya appeared earlier and were more severe. At 24th h after ischemia immunoreactivity of most of the neurons and synapses was similar to this in normal control animals. Morphologically unchanged asymmetric synapses were present in all experimental groups. The presented data confirm high vulnerability of GABAergic neuronal population of the thalamic reticular nucleus to ischemia and suggest transient nature of postischemic GABAergic insufficiency.
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PMID:Ischemia inhibits GABAergic neurons of the rat thalamic reticular nucleus. An immunocytochemical study. 798 26

The present study was undertaken to explore changes in neurotransmitters and neuromodulators of brain regions impaired by microsphere embolism-induced, sustained ischemia. Nine hundred microspheres (48 microns) were injected into the right internal carotid artery of rats, and the time course of changes in the triphenyltetrazolium chloride (TTC)-stained areas of their brain slices and acetylcholine and amino acid contents in the cerebral cortex, striatum and hippocampus of both hemispheres were determined. The TTC-unstained area, a measure of infarction, was developed in the right hemisphere by the 3rd day after the embolism, which was similar to that on the 28th day. A marked decline in acetylcholine content of these three regions of the right hemisphere was detected throughout the experiment (28 days). The glutamate, aspartate, GABA, and taurine levels were markedly decreased following microsphere-embolism. Most of these decreases were significantly attenuated during the first 5 days following the embolism, and they then partially recovered with time after the operation. Minor metabolic changes were observed in the left hemisphere. The results suggest that microsphere-embolism induces cerebral infarction and/or sustained damage to acetylcholine and neurotransmitter amino acid synthesis and/or catabolism of the brain regions. This model may provide information concerning the pathophysiological alterations in long-term cerebral ischemia and infarction.
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PMID:Sustained changes in acetylcholine and amino acid contents of brain regions following microsphere embolism in rats. 810 24

Although considerable evidence supports a role for amino acids in transient global cerebral ischemia and permanent focal cerebral ischemia, effects of transient focal cerebral ischemia on the extracellular concentrations of amino acids have not been reported. Accordingly, our study was undertaken to examine the patterns of changes of extracellular glutamate, aspartate, GABA, taurine, glutamine, alanine, and phosphoethanolamine in the striatum of transient focal cerebral ischemia, as evidence to support their pathogenic roles. Focal ischemia was induced using the middle cerebral artery occlusion model, with no need for craniotomy. Microdialysis was used to sample the brain's extracellular space before, during, and after the ischemic period. One hour of middle cerebral artery occlusion followed by recirculation caused neuronal damage that was common in the frontoparietal cortex and the lateral segment of the caudate nucleus. During 1 h of ischemia, the largest increase occurred for GABA and moderate increases were observed for taurine, glutamate, and aspartate. Alanine, which is a nonneuroactive amino acid, increased little. After recirculation, the levels of glutamate and aspartate reverted to normal baseline values right after reperfusion. Despite these rapid normalizations, neuronal damage occurred. Therefore, uptake of excitatory amino acids can still be restored after 1 h of middle cerebral artery occlusion, and tissue damage occurs even though high extracellular levels of glutamate are not maintained.
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PMID:Changes in the extracellular concentrations of amino acids in the rat striatum during transient focal cerebral ischemia. 811 94

The concentrations of amino acids (AA), stroke index and infarct area were determined in 26 gerbils which were divided into 3 groups: RSM-treated (n = 8), Saline-treated (n = 10) and sham-operated (n = 8). The levels of AA were measured with microdialysis technique in cerebral cortex. The concentrations of neurotransmitter AA, as Glu and GABA and Asp, were significantly increased during the first 60 min after CCA ligation, while the concentrations of non-neurotransmitter AA, as Thr and Ser, had no significant changes. In RSM-treated gerbils, the level of Glu was significantly lower than that of the saline-treated, but the GABA in RSM-treated was significantly higher than that of the saline-treated. The ratio of Glu/GABA was significantly decreased after ischemia. The RSM could improve the reduction of ratio of Glu/GABA during 0-30 min and 91-120 min after cerebral ischemia. There were statistically significant decrease in terms of stroke index in RSM-treated group when compared with saline-treated group at 24 h and 16 h after CCA ligation respectively. The RSM has a tendency to decrease the size of infarct area, but no statistical difference. The results suggest that the neurotransmitter AA involve in the pathophysiological procedures of cerebral ischemia and the RSM can attenuate dysfunctions of EAA and IAA. Furthermore, the results also imply that there may be an alternate way to treat cerebral ischemia by inhibiting the presynaptic releasing of Glu and stimulating the releasing of GABA.
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PMID:Effect of radix salviae miltiorrhizae on EAA and IAA during cerebral ischemia in gerbils: a microdialysis study. 819 18

Inhibitory neurotransmission may play an important role in neuronal degeneration following transient cerebral ischemia. We studied the effect of transient forebrain ischemia on the GABAA receptor system in the gerbil hippocampus. Gerbils were subjected to 5 minutes of bilateral carotid occlusion and were sacrificed at various times over 4 days following reperfusion. There was a substantial loss of pyramidal cells in the CA1 area of the hippocampus 4 days following ischemia. No cell loss was detected in CA3 pyramidal cells of the hippocampus, granule cell layer of the dentate gyrus, and ventroposterior medial and ventroposterior lateral nuclei of the thalamus at any time following ischemia. Examination of brain slices by in situ hybridization histochemistry revealed that a change in expression of the GABAA receptor alpha 1 and beta 2 subunit mRNAs occurred in two phases following onset of reperfusion. The early phase (rapid) occurred within the first 4 hours following reperfusion. The expression of mRNAs significantly decreased (up to 25%) within 1 hour after occlusion in CA1 and CA3 pyramidal cell layers of the hippocampus and in the granule cell layer of the dentate gyrus. The expression of the mRNAs in these regions continued to decrease for 4 hours (up to 43%). In the second phase, which began between 4 and 12 hours following reperfusion, mRNA expression started to return to control levels in CA3 hippocampus and in the dentate. However, expression of both mRNAs continued to decline slowly in the CA1 pyramidal cell layer (up to 85%) over the next 3 days, concomitantly with degeneration of the CA1 pyramidal cells. Expression of mRNAs in the ventroposterior medial or ventroposterior lateral nuclei of the thalamus was similar to control values. To determine if a change in GABAA receptor distribution paralleled changes in receptor subunit mRNA expression, we also measured the binding of [35S]t-butylbicyclophosphorothionate to GABAA receptor chloride channels. The t-butylbicyclophosphorothionate [35S] binding decreased between 1 and 4 days after reperfusion in the dendritic fields of CA1 pyramidal cells (strata oriens, radiatum, and lacunosum-moleculare) but not in the pyramidal cell body layer. These results indicate that expression of GABAA receptor subunit mRNAs decrease well before CA1 pyramidal cell degeneration and loss of GABAA receptors. At present, it is not clear if an early loss of mRNA expression after an ischemic insult leads to a functional defect in GABAA receptors. If so, a loss of GABA neurotransmission may contribute to the development of neuronal degeneration following cerebral ischemia.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Rapid decline of GABAA receptor subunit mRNA expression in hippocampus following transient cerebral ischemia in the gerbil. 826 42


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