Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0917798 (cerebral ischemia)
 17,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In contrast to cardiovascular disease, the impact of nutritional status on the prevention and outcome of stroke has received limited investigation. We present a mechanism based on animal studies, clinical data, and epidemiological data by which protein-energy status in the acute stroke and immediate postinjury periods may affect outcome by regulating reduced glutathione (GSH), a key component of antioxidant defense. As cysteine is the limiting amino acid for GSH synthesis, the GSH concentration of a number of nonneural tissues has been shown to be decreased by fasting, low-protein diets, or diets limiting in sulfur amino acids. The mechanism may also be relevant in brain since GSH in some brain regions is responsive to dietary sulfur amino acid supply and to the pro-cysteine drug, L-2-oxothiazolidine-4-carboxylate. The latter is an intracellular cysteine delivery system used to overcome the toxicity associated with cysteine supplementation. These findings may provide the mechanism to explain both the inverse correlation between dietary protein and stroke mortality and the documented association between suboptimal protein-energy status and diminished functional status following a stroke. Future investigations should examine the role of nutritional intervention in neuroprotective strategies aimed at improving stroke outcome. Pharmacological interventions such as L-2-oxothiazolidine-4-carboxylate should be investigated in animal models of stroke, as well as the impact of nutritional status on the response to these agents. Finally, micronutrient deficiencies that may accompany protein-energy malnutrition, such as selenium, should also be investigated for their role in antioxidant defense in cerebral ischemia.
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PMID:Nutritional regulation of glutathione in stroke. 1283 6

Two compounds that deplete glutathione (buthionine sulfoximine and diethyl maleate) with different mechanisms of action decrease body temperature and increase tolerance to complete global cerebral ischemia, both correlating closely with the glutathione concentration decrease. Glutathione apparently participates in the regulations of these functional parameters. GSH diethyl ester does not influence the latter, though it increases moderately the GSH concentration. Injection of GSH ester into the cerebral ventricles or subcutaneously selectively increases the GSH level in the brain and liver. An influence of the brain on the glutathione system in the liver was revealed. Diethyl maleate and GSH ester increase the activity of glutathione metabolizing enzymes under certain conditions.
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PMID:Influence of changes in glutathione concentration on body temperature and tolerance to cerebral ischemia. 1288 35

Reactive oxygen species produced by neutrophils contribute to the pathogenesis of focal cerebral ischemia/reperfusion injury and signal the inflammatory response. We have previously shown that honokiol, an active principle extracted from Magnolia officinalis, has a protective effect against focal cerebral ischemia/reperfusion injury in rats that paralleled a reduction in reactive oxygen species production by neutrophils. To elucidate the underlying mechanism(s) of the antioxidative effect of honokiol, peripheral neutrophils isolated from rats were activated with phorbol-12-myristate-13-acetate (PMA) or N-formyl-methionyl-leucyl-phenylalanine (fMLP) in the presence or absence of honokiol. In this study, we found that honokiol inhibited PMA- or fMLP-induced reactive oxygen species production by neutrophils by three distinct mechanisms: (1) honokiol diminished the activity of assembled-NADPH oxidase, a major reactive oxygen species producing enzyme in neutrophils by 40% without interfering with its protein kinase C (PKC)-dependent assembly; (2) two other important enzymes for reactive oxygen species generation in neutrophils, i.e., myeloperoxidase and cyclooxygenase, were also inhibited by honokiol by 20% and 70%, respectively; and (3) honokiol enhanced glutathione (GSH) peroxidase activity by 30%, an enzyme that triggers the metabolism of hydrogen peroxide (H2O2). These data suggested that honokiol, acting as a potent reactive oxygen species inhibitor/scavenger, could achieve its focal cerebral ischemia/reperfusion injury protective effect by modulating enzyme systems related to reactive oxygen species production or metabolism, including NADPH oxidase, myeloperoxidase, cyclooxygenase, and GSH peroxidase in neutrophils.
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PMID:The anti-inflammatory effect of honokiol on neutrophils: mechanisms in the inhibition of reactive oxygen species production. 1295 55

The central nervous system reserves high concentrations of free Zn(2+) in certain excitatory synaptic vesicles. In pathological conditions such as transient cerebral ischemia, traumatic brain injury, and kainic acid (KA)-induced seizure, free Zn(2+) is released in excess at synapses, which causes neuronal and glial death. We report here that glutathione (GSH) can be used as an effective means for protection of neural cells from Zn(2+)-induced cell death in vitro and in vivo. Chronic treatment with 35 microM Zn(2+) led to death of primary cortical neurons and primary astrocytes. The Zn(2+) toxicity of cortical neurons was partially protected by 1 mM of GSH, whereas the Zn(2+) toxicity of primary astrocyte cultures was blocked completely by 100 microM of GSH. To evaluate the beneficial effects of GSH in vivo, an excitotoxin-induced neural cell death model was established by intracerebroventricular (i.c.v.) injection of 0.94 nmol (0.2 microg) KA, which produced selective neuronal death, especially in CA1 and CA3 hippocampal regions. The i.c.v. co-injection of 200 pmol of GSH significantly attenuated KA-induced neuronal cell death and reactive gliosis in hippocampus. The results of this study suggest the contribution of Zn(2+) in the excitotoxin-induced neural cell death model and a potential value of GSH as a therapeutic means against Zn(2+)-induced pathogenesis in brain.
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PMID:Protective effects of extracellular glutathione against Zn2+-induced cell death in vitro and in vivo. 1463 24

Oxidative stress plays an important role in the development of tissue damage following transient focal cerebral ischaemia. Glutathione is a central component in the antioxidant defence of cells. We have previously shown a close association between mitochondrial glutathione loss and cell death following middle cerebral artery (MCA) occlusion. Glutathione monoethyl ester increases cellular glutathione and is particularly effective in increasing the mitochondrial pool. In the present investigation, we infused glutathione monoethyl ester into the third ventricle during 2 h of MCA occlusion and 48 h of reperfusion. Infarct size was reduced from 46% of the total ischaemic hemisphere in saline-treated animals to 16% following ester treatment. Thus, glutathione monoethyl ester provides neuroprotection following transient focal cerebral ischaemia.
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PMID:Glutathione monoethyl ester provides neuroprotection in a rat model of stroke. 1469 63

There is evidence that the excessive generation of reactive oxygen free radicals contributes to the brain injury associated with cerebral ischemia. In the present study, the protective effect of chronic administration of ethyl docosahexaenoate (E-DHA) against oxidative brain injury was evaluated in the gerbil model of transient cerebral ischemia. Weanling male gerbils were orally pretreated with either E-DHA (200 mg/kg) or vehicle, once a day, for 10 weeks and subjected to bilateral occlusion of common carotid arteries for 10 min. At the different reperfusion times, E-DHA pretreatment significantly inhibited the increases in the production of brain salicylate-derived 2,5-dihydroxybenzoic acid (2,5-DHBA) and content of brain malonildialdehyde (MDA). The superoxide dismutase (SOD) activity was not modified; however, pretreatment with E-DHA significantly prevented the level of brain-reduced glutathione (GSH) and activities of brain glutathione peroxidase (GSH-P(X)) and catalase (CAT) from declines caused by cerebral ischemia. Moreover, ischemia and reperfusion-induced delayed neuronal loss in the hippocampus CA1 sector and locomotor hyperactivity were also significantly attenuated by pretreatment with E-DHA. These results suggested that the neuroprotective effect of E-DHA might be due to its antioxidant property.
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PMID:Protective effect of chronic ethyl docosahexaenoate administration on brain injury in ischemic gerbils. 1558 73

This study was conducted to investigate the neuroprotective effects of 20(S)-ginsenoside Rg3 on focal cerebral ischemia in rats. Middle cerebral artery occlusion (MCAO) model in male Wistar-Kyoto (WKY) rats was employed. The behavioral tests were used to evaluate the damage to central nervous system. The infarct area of brain was assessed in the brain slices stained with 2,3,5-triphenyltetrazolium chloride (TTC). Hydrogen clearance techniques were used to monitor regional cerebral blood flow (rCBF), spectrophotometric assay methods were used to determine the activities of superoxide dismutase (SOD) and glutathione-peroxidase (GSH-Px), contents of malondialdehyde (MDA) and adenosine triphosphate (ATP) of the brain. Furthermore, the respiratory control ratio (RCR=State 3/State 4) was assessed in the brain mitochondria. The results showed that sublingual vein injection of 20(S)-ginsenoside Rg3 at doses of 10 and 5 mg kg(-1), but not 2.5 mg kg(-1) exhibited significant neuroprotective effects on rats against focal cerebral ischemic injury by markedly decreasing neurological deficit scores, reducing the infarct area and enhancing the rCBF compared with the control group. At the same time, 20(S)-ginsenoside Rg3 significantly improved mitochondrial energy metabolism, antagonized decreases in SOD and GSH-Px activities and increase in MDA level induced by cerebral ischemia. All these findings suggest that 20(S)-ginsenoside Rg3 might provide neuroprotection against the cerebral ischemia-induced injury in rat brain through reducing lipid peroxides, scavenging free radicals and improving the energy metabolism.
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PMID:Neuroprotective effect of 20(S)-ginsenoside Rg3 on cerebral ischemia in rats. 1564 71

Overexpression of copper/zinc superoxide dismutase (SOD1) in transgenic mice protects from transient focal cerebral ischemia in adult animals, but increases oxidative injury in perinatal mice. The effect of SOD1 overexpression on astrocytes subjected to ischemia-like insults has not yet been determined. Overexpression of human SOD1 in astrocytes resulted in a 3-fold increase in SOD1 activity without coupled up-regulation of catalase or glutathione peroxidase activities. Cells subjected to oxygen-glucose deprivation (OGD) or glucose deprivation to mimic ischemic injury were protected by SOD1 overexpression. OGD injury was reduced 47.6+/-9.3%, assessed by release of lactate dehydrogenase. OGD also caused a significant increase in catalase activity which was moderated by SOD1 overexpression. The level of glutathione in astrocytes overexpressing SOD1 was maintained at higher levels following 5 h OGD compared to control cultures under the same conditions. Reduction of glutathione prior to OGD significantly increased cell death of SOD1-overexpressing astrocytes as well as controls, but SOD1 still provided significant protection, suggesting that both GSH-dependent scavenging and GSH-independent scavenging are relevant to SOD1 protection in astrocytes.
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PMID:Overexpression of copper/zinc superoxide dismutase decreases ischemia-like astrocyte injury. 1578 Jul 69

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

Methodic approaches for the purposeful changes of glutathione concentration in the brain and liver by administration of glutathione depletors and prodrugs have been modified. Two different depletors (diethylmaleate and buthionine sulfoximine) cause considerable increase of tolerance to the complete global cerebral ischemia and hypothermia development which correlate closely with the decrease of GSH concentration. Five GSH prodrugs (GSH esters and oxothiazolidine carboxilate) and GSH itself usually decrease slightly body temperature but do not influence tolerance to ischemia in the most of series. The increase of tolerance to the complete global cerebral ischemia is connected not with GSH accumulation, but with its decrease. Evidently one of the two opposite GSH effects, sensitizing or protecting one, can predominate in different forms of cerebral ischemia.
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PMID:[The correlation of tolerance to cerebral ischemia and body temperature with glutathione concentration]. 1611 94


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