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

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

The antioxidant enzymatic system in brain hypoperfusion/reperfusion model in rats after spermine administration was evaluated. Incomplete cerebral ischemia/reperfusion induced by temporal occlusion of common carotid arteries caused a decrease in the activities of superoxide dismutase and glutathione reductase as well as total and free sulfhydryl groups, while thiobarbituric acid-reactive substances became elevated. Administration of spermine after the reperfusion led to restoring all above parameters to normal values. Protective effect of spermine in transiently hypoperfused and subsequently reperfused rat brain is briefly discussed.
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PMID:Spermine protects in vivo the antioxidant enzymes in transiently hypoperfused rat brain. 871 55

Both acidosis and oxidative stress contribute to ischemic brain injury. The present study examines interactions between acidosis and oxidative stress in murine cortical cultures. Acidosis (pH 6.2) was found to potentiate markedly neuronal death induced by H2O2 exposure. To determine if this effect was mediated by decreased antioxidant capacity at low pH, the activities of several antioxidant enzymes were measured. Acidosis was found to reduce the activities of glutathione peroxidase and glutathione S-transferase by 50-60% (p < 0.001) and the activity of glutathione reductase by 20% (p < 0.01) in lysates of the cortical cultures. Like acidosis, direct inhibition of glutathione peroxidase with mercaptosuccinate also potentiated H2O2 toxicity. Because acidosis may accelerate hydroxyl radical production by the Fenton reaction, the effect of iron chelators was also examined. Both desferrioxamine and N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine, two structurally different iron chelators, significantly reduced H2O2-induced neuronal death under both pH 7.2 and pH 6.2 conditions. These results suggest that the increased cell death produced by severe acidosis during cerebral ischemia may result in part from exacerbation of oxidative injury. This exacerbation may result from both impaired antioxidant enzyme functions and increased intracellular free iron levels.
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PMID:Acidosis potentiates oxidative neuronal death by multiple mechanisms. 1050 Dec

The time course of oxidative damage in different brain regions was investigated in the gerbil model of transient cerebral ischemia. Animals were subjected to both common carotid arteries occlusion for 5 min. After the end of ischemia and at different reperfusion times (2, 6, 12, 24, 48, 72, 96 h and 7 days), markers of lipid peroxidation, reduced and oxidized glutathione levels, glutathione peroxidase, glutathione reductase, manganese-dependent superoxide dismutase (MnSOD) and copper/zinc containing SOD (Cu/ZnSOD) activities were measured in hippocampus, cortex and striatum. Oxidative damage in hippocampus was maximal at late stages after ischemia (48-96 h) coincident with a significant impairment in glutathione homeostasis. MnSOD increased in hippocampus at 24, 48 and 72 h after ischemia, coincident with the marked reduction in the activity of glutathione-related enzymes. The late disturbance in oxidant-antioxidant balance corresponds with the time course of delayed neuronal loss in the hippocampal CA1 sector. Cerebral cortex showed early changes in oxidative damage with no significant impairment in antioxidant capacity. Striatal lipid peroxidation significantly increased as early as 2 h after ischemia and persisted until 48 h with respect to the sham-operated group. These results contribute significant information on the timing and factors that influence free radical formation following ischemic brain injury, an essential step in determining effective antioxidant intervention.
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PMID:Time course of oxidative damage in different brain regions following transient cerebral ischemia in gerbils. 1167 36

Cytidine-5'-diphosphocholine (citicoline or CDP-choline), an intermediate in the biosynthesis of phosphatidylcholine (PtdCho), has shown beneficial effects in a number of CNS injury models and pathological conditions of the brain. Citicoline improved the outcome in several phase-III clinical trials of stroke, but provided inconclusive results in recent clinical trials. The therapeutic action of citicoline is thought to be caused by stimulation of PtdCho synthesis in the injured brain, although the experimental evidence for this is limited. This review attempts to shed some light on the properties of citicoline that are responsible for its effectiveness. Our studies in transient cerebral ischemia suggest that citicoline might enhance reconstruction (synthesis) of PtdCho and sphingomyelin, but could act by inhibiting the destructive processes (activation of phospholipases). Citicoline neuroprotection may include: (i) preserving cardiolipin (an exclusive inner mitochondrial membrane component) and sphingomyelin; (ii) preserving the arachidonic acid content of PtdCho and phosphatidylethanolamine; (iii) partially restoring PtdCho levels; (iv) stimulating glutathione synthesis and glutathione reductase activity; (v) attenuating lipid peroxidation; and (vi) restoring Na(+)/K(+)-ATPase activity. These observed effects of citicoline could be explained by the attenuation of phospholipase A(2) activation. Based on these findings, a singular unifying mechanism has been hypothesized. Citicoline also provides choline for synthesis of neurotransmitter acetylcholine, stimulation of tyrosine hydroxylase activity and dopamine release.
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PMID:Citicoline: neuroprotective mechanisms in cerebral ischemia. 1179 39

Stroke, or ischaemic brain damage, is of great geriatric importance being the third most common cause of death after cancer and heart diseases in developed countries. Despite such high frequency, its management has received inadequate attention. Many studies have shown the role of free radicals in the pathogenesis of ischaemic brain damage. Search for safe and effective antioxidant and free radial scavenger agents, therefore, appear to be a promising approach for stroke therapy. Gold, widely used in modern medicine for the treatment of rheumatoid arthritis, is highly valued for various medicinal uses in Indian systems of medicine. Traditional gold preparations are attributed with tonic/rejuvenating and antioxidant properties. Our earlier studies revealed interesting analgesic, immunostimulant, adaptogenic and glycogen sparing properties in these preparations, but their effects in cerebral ischaemia have not been investigated. This prompted us to initiate the present study using global and focal models of ischaemia in albino rats. Enzymatic parameters (lipid peroxidase, reduced glutathione, catalase, glutathione reductase, glutathione-S-transferase, glutatione peroxidase, superoxide dismutase, and glucose-6-phosphate dehydrogenase) were employed to assess ischaemic brain damage and its modulation. Significant restoration of altered values to near normal levels by Ayurvedic Swarna Bhasma and Unani Kushta Tila Kalan (25 mg/kg, orally for 10 days), suggest potentials for gold preparations in cerebrovascular diseases. The preparations deserve more scientific attention for possible therapeutic exploitation.
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PMID:Antioxidant/restorative effects of calcined gold preparations used in Indian systems of medicine against global and focal models of ischaemia. 1207 6

Fructose-1,6-bisphosphate (FBP), an endogenous intermediate of glycolysis, protects the brain against ischemia-reperfusion injury. The mechanisms of FBP protection after cerebral ischemia are not well understood. The current study was undertaken to determine whether FBP protects primary neurons against hypoxia and oxidative stress by preserving reduced glutathione (GSH). Cultures of pure cortical neurons were subjected to oxygen deprivation, a donor of nitric oxide and superoxide radicals (3-morpholinosydnonimine), an inhibitor of glutathione synthesis (L-buthionine-sulfoximine) or glutathione reductase (1,3-bis(2-chloroethyl)-1-nitrosourea) in the presence or absence of FBP (3.5 mM). Neuronal viability was determined using an 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay. FBP protected neurons against hypoxia-reoxygenation and oxidative stress under conditions of compromised GSH metabolism. The efficacy of FBP depended on duration of hypoxia and was associated with higher intracellular GSH concentration, an effect partly mediated via increased glutathione reductase activity.
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PMID:Fructose-1,6-bisphosphate preserves intracellular glutathione and protects cortical neurons against oxidative stress. 1250 61

The effect of Khamira Abresham Uood Mastagiwala (KAUM) (a preparation of Indian System of Unani Medicine) on the activity of antioxidant enzymes, glutathione reductase (GR), glutathione S-transferase (GST), glutathione peroxidase (GPx), catalase (CAT) and the content of glutathione (GSH) and thiobarbituric acid reactive substances (TBARS) was studied in the middle cerebral artery occluded (MCAO) rats after 15 days pretreatment (200 mg/kg body weight (b.wt.), orally) of Khamira Abresham Uood Mastagiwala. The rats were trained and assessed for neurobehavioral activity using Cook's climbing pole. The middle cerebral artery of adult male Wistar rats was occluded for 2 h and reperfused for 22 h. The activity of GPx, GST, GR, catalase and content of GSH was decreased significantly in MCAO group as compared with sham. The rats of MCAO + KAUM group have shown a significant protection in the activity of above-mentioned antioxidant enzymes and content of glutathione when compared with MCAO group. The significantly elevated level of TBARS in MCAO group was depleted significantly by the pretreatment of animals with KAUM in MCAO group. The neurobehavioral assessment has also strengthened the above biochemical data thereby indicating that the therapeutic intervention of KAUM, which is a potent cardiac and melancholic tonic, can be used to prevent or reduce the deterioration caused by free radicals thereby preventing subsequent pathological and biochemical changes which occur during cerebral ischemia.
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PMID:Protective effect of Khamira Abresham Uood Mastagiwala against free radical induced damage in focal cerebral ischemia. 1589 24

Active oxygen species alter the activities of the enzymes involved in the defence against free radicals and substantially influence the aging process and age-dependent neuropathology. Unilamellar liposomes were used to deliver flavonoidal antioxidant quercetin (QC) to rat brain. Antioxidant potential of QC loaded in mannosylated (QC 7.2 micromol/kg b.wt.) liposomes (50 nm) was investigated by an in vivo model of cerebral ischemia and reperfusion on Sprague Dawley young (2 months old, b.wt. 160-180 g) and aged (20 months old, b.wt. 415-440 g) rats. Animals were made ischemic for 30 min by bilateral clamping of the common carotid artery followed by a 30 min cerebral reperfusion by withdrawing the clamping. Diene level and (GSSG/GSH) ratio were found to be higher in normal aged, compared to normal young rat brain. Superoxide dismutase, catalase, glucose-6-phosphate dehydrogenase, glutathione reductase and glutathione S-transferase activities were lower in normal aged rat brain. Further reduction of these antioxidant enzymes was observed in aged rat brain by the induction of cerebral ischemia and reperfusion. Mannosylated liposomally encapsulated QC treatment resulted in a significant preservation of the activities of antioxidant enzymes and a marked inhibition of cellular edema formation in neuronal cells of young and old rats.
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PMID:Mannosylated liposomal flavonoid in combating age-related ischemia-reperfusion induced oxidative damage in rat brain. 1648 Jul 58

The modifying effects of Crocus sativus (CS) stigma extract on neurobehavioral activities, malondialdehyde (MDA), reduced glutathione (GSH), glutathione peroxidase, glutathione reductase, glutathione S-transferase, superoxide dismutase (SOD), catalase (CAT), and Na(+),K(+)-ATPase activities, and glutamate (Glu) and aspartate (Asp) content were examined in the middle cerebral artery (MCA) occlusion (MCAO) model of acute cerebral ischemia in rats. The right MCA of male Wistar rats was occluded for 2 hours using intraluminal 4-0 monofilament, and reperfusion was allowed for 22 hours. MCAO caused significant depletion in the contents of GSH and its dependent enzymes while significant elevation of MDA, Glu, and Asp. The activities of Na(+),K(+)-ATPase, SOD, and CAT were decreased significantly by MCAO. The neurobehavioral activities (grip strength, spontaneous motor activity, and motor coordination) were also decreased significantly in the MCAO group. All the alterations induced by ischemia were significantly attenuated by pretreatment of CS (100 mg/kg of body weight, p.o.) 7 days before the induction of MCAO and correlated well with histopathology by decreasing the neuronal cell death following MCAO and reperfusion. The present results may suggest the effectiveness of CS in focal ischemia most probably by virtue of its antioxidant property.
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PMID:Effect of Saffron (Crocus sativus) on neurobehavioral and neurochemical changes in cerebral ischemia in rats. 1682 11


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