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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

Oxygen-derived free radicals have been implicated in the pathogenesis of vasogenic edema and infarction caused by ischemia and reperfusion injury. In earlier studies, exogenously supplied liposome-entrapped CuZn superoxide dismutase (CuZn-SOD) ameliorated ischemic brain edema and infarction in rats following focal cerebral ischemia. To ascertain directly the role of SOD in the protection against superoxide radical-induced injury, we measured infarct size and water content 24 hr following focal cerebral ischemia in nontransgenic mice and in transgenic mice bearing the human SOD1 gene. These transgenic mice have 3.1-fold higher cellular CuZn-SOD activity in the brain than do their nontransgenic littermates. We also measured antioxidant levels (reduced glutathione and reduced ascorbate) of contralateral cortex, infarct cortex, surrounding cortex, and striatum. Infarct size and brain edema were significantly decreased in transgenic mice compared with nontransgenic mice. Reduced glutathione and reduced ascorbate levels decreased in the ischemic hemisphere, but levels in surrounding cortex and striatum were significantly higher in transgenic mice than in nontransgenic mice. These results indicate that increased endogenous SOD activity in brain reduces the level of ischemic damage and support the concept that superoxide radicals play an important role in the pathogenesis of infarction and edema following focal cerebral ischemia.
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PMID:Attenuation of focal cerebral ischemic injury in transgenic mice overexpressing CuZn superoxide dismutase. 176 30

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

Adenylate kinase activity was found in 32 of 34 samples of cerebrospinal fluid (CSF) from 21 patients with stroke and seven patients with global cerebral ischaemia (GCI). The light absorbance values of the spectrum 400-650 nm revealed the scanty occurrence of haemoglobin products in the CSF in some patients. No correlation was found between the absorbance values at 415 nm, reflecting oxyhaemoglobin, and the adenylate kinase activities. Thus, a main contribution to the adenylate kinase activity in CSF by leakage of this enzyme from erythrocytes could be ruled out. Instead increased leakiness of the brain cells, having an impaired metabolism due to insufficient supply of oxygen and glucose, was the most plausible cause of the findings. The quotient between the adenylate kinase activity and the light absorbance at 415 nm seemed to reflect the extent of ischaemically deranged brain tissue in the GCI patients, while the CSF-lactate values were not correlated to the clinical outcome. Glutathione, an intracellular tripeptide, was more often found in the CSF from GCI patients than from stroke patients.
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PMID:Cerebrospinal fluid markers of disturbed brain cell metabolism in patients with stroke and global cerebral ischemia. 625 76

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


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