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

1. Cerebral ischemia applied for 15 min and followed by a 30 min reperfusion did not change the glutathione (GSH) levels and beta-adrenoceptor density (Bmax) in brain cortex. 2. A significant increase in erythrocyte-lysate GSH concentration (vs control) and a significant decrease of Bmax values in erythrocyte membranes (vs control) was found at the same time. 3. Pretreatment with the alpha-adrenoceptor antagonist phentolamine (5 mg/kg i.p.) prevented the erythrocyte GSH increase but not the decrease of Bmax value. Pretreatment with the beta-antagonist propranolol (2 mg/kg i.p.) did not influence the increase in erythrocyte GSH but circumvented the decrease of Bmax.
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PMID:Glutathione mobilization during cerebral ischemia and reperfusion in the rat. 131 10

Oxygen free radicals have been implicated in the pathogenesis of brain injury induced by ischemia/reperfusion. We studied the role of endogenous reduced glutathione (GSH) in brain infarction associated with focal cerebral ischemia caused by permanent ligation of the right middle cerebral artery (MCA) and the right common carotid artery (CCA) plus temporary occlusion of the left CCA. GSH levels in the ischemic side of cortex decreased with time after ischemia and preceded cortical infarction estimated by the staining of mitochondrial respiratory enzymes with 2,3,5-triphenyltetrazolium chloride. GSH levels in the contralateral cortex were unchanged through the experimental periods. The extent of decrease of GSH levels and the severity of infarction in the ischemic cortex at 24 h after ischemia depended on the duration of occlusion of the left CCA. Depletion of brain GSH with buthionine sulfoximine, a selective inhibitor for gamma-glutamylcysteine synthetase, exacerbated cortical infarction and edema after ischemia. These results suggest that the endogenous brain GSH is an important determinant in the defense mechanisms against lesion formation after ischemia and support the possible role of oxygen radicals in the pathogenesis of ischemic brain injury.
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PMID:Depletion of brain glutathione by buthionine sulfoximine enhances cerebral ischemic injury in rats. 153 90

Substantial evidence exists that reactive oxygen species participate in the pathogenesis of brain damage following both sustained and transient cerebral ischemia, adversely affecting the vascular endothelium and contributing to the formation of edema. One likely triggering event for free radical damage is delocalization of protein-bound iron. The binding capacity for some iron-binding proteins is highly pH sensitive and, consequently, the release of iron is enhanced by acidosis. In this study, we explored whether enhanced acidosis during ischemia triggers the production of reactive oxygen species. To that end, enhanced acidosis was produced by inducing ischemia in hyperglycemic rats, with normoglycemic ones serving as controls. Production of H2O2, estimated from the decrease in catalase activity after 3-amino-1,2,4-triazole (AT) administration, was measured in the cerebral cortex, caudoputamen, hippocampus, and substantia nigra (SN) after 15 min of ischemia followed by 5, 15, and 45 min of recovery, respectively (in substantia nigra after 45 min of recovery only). Free iron in cerebrospinal fluid (CSF) was measured after ischemia and 45 min of recovery. Levels of total glutathione (GSH + GSSH) in cortex and hippocampus, and levels of alpha-tocopherol in cortex, were also measured after 15 min of ischemia followed by 5, 15, and 45 min of recovery. The results confirm previous findings that brief ischemia in normoglycemic animals does not measurably increase H2O2 production in AT-injected animals. Ischemia under hyperglycemic conditions likewise failed to induce increased H2O2 production. No difference in free iron in CSF was observed between animals subjected to ischemia under hyper- and normoglycemic conditions. The moderate decrease in total glutathione or alpha-tocopherol levels did not differ between normo- and hyperglycemic animals in any brain region or at any recovery time. Thus, the results failed to give positive evidence for free radical damage following brief periods of ischemia complicated by excessive acidosis. However, it is possible that free radical production is localized to a small subcellular compartment within the tissue, thereby escaping detection. Also, the results do not exclude the possibility that free radicals are pathogenetically important after ischemia of longer duration.
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PMID:Acidosis-induced ischemic brain damage: are free radicals involved? 205 Jul 47

Thirty minutes of total cerebral ischemia (decapitation) decreased total glutathione (GSH + GSSG) by 7% but had no detectable effect on the concentration of oxidized glutathione (GSSG), reduced ascorbate, or total ascorbate, In a model of reversible, bilateral hemispheric ischemia (four-vessel occlusion) no changes in glutathione or ascorbate were detected after 30 min of ischemia. During 24 h of reperfusion following such an insult no detectable change in total ascorbate, reduced ascorbate, or oxidized glutathione was noted: however, total brain glutathione declined by 25%. The findings are discussed in relation to the hypothesis that the deleterious effects of ischemia are due to an increase in free radical production which in turn leads to increased lipid peroxidation.
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PMID:Glutathione and ascorbate during ischemia and postischemic reperfusion in rat brain. 745 15

The status of glutathione (GSH) and protein thiol homeostasis was examined in rat brain regions during reperfusion after moderate and severe cerebral ischemia. GSH levels were decreased in brain regions during reperfusion for 1 hr after moderate or severe ischemia for 0.5 hr. Maximal loss of GSH (50-66%) was observed in the striatum and hippocampus. The GSH lost from the brain regions was essentially recovered as protein-glutathione mixed disulfide (PrSSG) with concomitant loss of protein thiols (PrSH). The activities of enzymes such as Na+K+ ATPase, NADH dehydrogenase and glutathione reductase were also inhibited but were restored after incubation of the brain homogenate with dithiothreitol. The depletion of GSH was also accompanied by an increase in the levels of malondialdehyde and reactive oxygen species. The total GSH recovered as sum of GSH and PrSSG was significantly higher than the sham-operated controls in the hippocampus and striatum after 1 hr of reperfusion, after moderate ischemia for 0.5 hr, and at the end of 24 hr of reperfusion the GSH-protein thiol homeostasis was restored. In contrast after 1 hr of reperfusion after severe ischemia, the GSH recovered as sum of GSH and PrSSG was not significantly different from sham-operated controls and at the end of 24 hr, 7 of 9 animals died. The recuperation of the brain from oxidative stress during reperfusion after moderate ischemia was thus preceded by increased recovery of total GSH essentially in the form of PrSSG. Thus, rapid restoration of thiol homeostasis in the brain during reperfusion may help the brain recover from reperfusion injury.
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PMID:Glutathione and protein thiol homeostasis in brain during reperfusion after cerebral ischemia. 756 84

Ascorbate and glutathione (GSH) are the primary water-soluble antioxidants in the CNS. Oxidative stress, sometimes indicated by loss of these antioxidants, has been linked to several clinical and experimental conditions, including cerebral ischemia. These conditions are also gender-linked, with greater incidence or severity in males than females. To test whether there are gender differences in oxidant/antioxidant regulation, we determined basal levels of ascorbate and GSH in rat brain and their loss after 1 h decapitation ischemia. We found that ascorbate levels in male rat brain were 7-10% higher than in females, depending on region, whereas GSH levels were gender-independent. Significant ascorbate loss (up to 12%) occurred in males during ischemia, with a regional pattern of cerebellum > hippocampus > prefrontal cortex. Loss of ascorbate in females was not significant in any region. By contrast, loss of GSH was significant in both males and females. Greater loss of GSH than ascorbate was in agreement with previous studies and was consistent with loss from enzymatic degradation, as well as oxidation. The significant gender difference in ascorbate loss, as a marker of oxidative stress, supports the hypothesis that inherent differences in oxidant/antioxidant regulation contribute to gender differences in response to ischemia and other pathological conditions.
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PMID:Gender differences in cerebral ascorbate levels and ascorbate loss in ischemia. 757 30

A method for the continuous monitoring of extracellular glutathione (GSH) concentrations in rat brain has been developed. This method involved the in vivo sampling of brain extracellular fluid by microdialysis perfusion and the subsequent analysis by high-performance liquid chromatography (HPLC) with fluorescence detection. Perfusates from the microdialysis probes were directly derivatized with methanolic monobromobimane which acted as the fluorescence tag. Separation of the derivatized perfusate was achieved on narrow-bore reversed-phase C18 columns. Recoveries of GSH from the microdialysis probes ranged from 1.5% to 4%. The basal extracellular GSH concentration in rat (Sprague-Dawley) brain cortex was found to be 2.10 +/- 1.78 microM (mean +/- S.D.) (results of 18 rats). Fluorescence detection and separation on narrow-bore columns provided adequate sensitivity for accurate determination of brain extracellular GSH concentrations in rats. With this method, the extracellular GSH concentrations in the cerebral cortex were found to be significantly elevated upon the onset of cerebral ischemia induced by the ligation of bilateral common carotid arteries.
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PMID:Determination of extracellular glutathione in rat brain by microdialysis and high-performance liquid chromatography with fluorescence detection. 789 62

Effects of YM737[N-(N-r-L-glutamyl-L-cysteinyl)glycine 1-isopropyl ester sulfate monohydrate], a new glutathione (GSH) analog more readily transported into cells than GSH, on cerebral ischemia were compared with those of GSH and some other drugs in rats subjected to occlusion of the bilateral carotid arteries. YM737 significantly reduced lethality, increased brain-water levels as measured by both dry-wet and NMR methods, and increased malondialdehyde (MDA) levels in the cerebral ischemic rats. On the other hand, pharmacological actions of GSH itself was less than those of YM737. In the ischemic rats used in the present study, there was no significant difference in 31P-NMR signals between the normal and the cerebral ischemic rats. These results suggest that YM737 showed anti-cerebral ischemic effects presumably due, in part, to inhibition of lipid peroxidative responses.
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PMID:Protective actions of YM737, a new glutathione analog, against cerebral ischemia in rats. 821 Jul

The transport of glutathione (GSH) or glutathione isopropyl ester (GSH isopropyl ester) to the cerebrospinal fluid (CSF) in rats was estimated by levels of GSH or GSH isopropyl ester and their metabolites in CSF 30 min after the intravenous administration of GSH or GSH isopropyl ester (300 mg/kg). Although the CSF uptake of GSH isopropyl ester was almost equal to that of GSH as evidenced by about a two-fold increase in the amount of non-protein sulfhydryl groups in CSF, the sum of GSH isopropyl ester and GSH concentrations in the CSF after GSH isopropyl ester treatment was increased by 32% compared with saline-treated controls. On the other hand, treatment with GSH had no significant increase in GSH levels in CSF but increased its metabolite levels, such as cysteinyl-glycine and cysteine. GSH isopropyl ester was less metabolized than GSH. GSH isopropyl ester had low affinity to purified gamma-glutamyl transpeptidase, a key enzyme for metabolism of GSH in the choroid plexus, supporting the finding that GSH isopropyl ester is more stable than GSH in CSF. These results are compatible with our previous report (Yamamoto et al. (1993) showing that the protective action of GSH isopropyl ester against cerebral ischemia was greater than that of GSH in rats. GSH isopropyl ester may be a useful agent which protects the brain from the damage associated with oxygen-related toxicities by increasing GSH levels in the CSF.
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PMID:Transport and metabolism of glutathione isopropyl ester in cerebrospinal fluid. 856 90

The effect of lowered brain glutathione content on the glutamate release following cerebral ischemia was investigated. Diethylmaleate (4 mmol/kg, i.p.), a commonly used chemical reagent for tissue glutathione depletion, significantly reduced the ischemia-induced glutamate release. The release of another excitatory amino acid aspartate was not affected by the diethylmaleate administration. These results suggested that part of the elevated glutamate content induced by ischemia might result from the cellular GSH.
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PMID:Lowered brain glutathione by diethylmaleate decreased the glutamate release induced by cerebral ischemia in anesthetized rats. 858 90


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