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)

Spiramine T, an atisine-type diterpene alkaloid isolated from the Chinese herbal medicine Spiraea japonica var. acuta (Rosaceae), was shown to have neuroprotective effects on cerebral ischemia-reperfusion injury. In this study, the effects of spiramine T on antioxidant enzymes and nitric oxide production were evaluated in gerbils subjected to global forebrain ischemia (10 min) and reperfusion (5 days). Spiramine T (1.0 and 2.0 mg kg(-1) i.p.) markedly reduced the content of lipid peroxide (LPO), increased the glutathione peroxidase (GSH-PX) activity, and inhibited the increase of nitric oxidase (NOS) activity and nitric oxide production in the cortex during ischemia-reperfusion in gerbils. These results suggested that the neuroprotective effects of spiramine T were related to modulation of endogenous antioxidant enzymatic activities and reduction of the formation of nitric oxide.
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PMID:Effects of spiramine T on antioxidant enzymatic activities and nitric oxide production in cerebral ischemia-reperfusion gerbils. 1210 82

A timed profile of glutathione oxidation and reactive nitrogen species during reperfusion after cerebral ischemia in rat was obtained. Dialysate was collected every 25 min from a microdialysis probe inserted into the cerebral cortex before and after cerebral ischemia. NO2-, NO3-, and reduced and oxidized glutathione (GSH, GSSG) were detected by high-performance liquid chromatography. GSH and GSSG increased and reached a peak: 3408 +/- 1710% (mean +/- SE) at 25 min of reperfusion (P < 0.0001) and 329 +/- 104% at 50 min of reperfusion (P = 0.06), respectively. Oxidation ratio decreased from 0.82 +/- 0.04 to 0.42 +/- 0.07 (P < 0.0001) at 25 min of reperfusion. NO3- levels significantly decreased (68.3 +/- 9.1%) (P < 0.01) during ischemia and remained lower than the control value during reperfusion. NO2- levels did not significantly change. These data suggest that GSH releases during early phase of reperfusion and that its rapid oxidation contributes to prevent an increase in reactive nitrogen species.
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PMID:Relationship between oxidation of glutathione and reactive nitrogen species during the early-reperfusion phase of cerebral ischemia. 1219 54

Oxidative stress is believed to be implicated in the pathogenesis of postischaemic cerebral injury. Many antioxidants were shown to be neuroprotective in experimental models of cerebral ischaemia/reperfusion (I/R). The present study was designed to investigate the potential protective effects of curcumin (CUR) against I/R insult in rat forebrain. The model adopted was that of surgically-induced forebrain ischaemia, performed by means of bilateral common carotid artery occlusion (BCCAO) for 1 h, followed by reperfusion for another 1h. The effects of a single i.p. dose of CUR (50, 100 or 200 mg kg(-1)), administered 0.5 h after the onset of ischaemia, were investigated by assessing oxidative stress-related biochemical parameters in rat forebrain. CUR, at the highest dose level (200 mg kg(-1)), decreased the I/R-induced elevated xanthine oxidase (XO) activity, superoxide anion (O(2)*(-)) production, malondialdehyde (MDA) level and glutathione peroxidase (GPx), superoxide dismutase (SOD), and lactate dehydrogenase (LDH) activities. On the other hand, CUR did not affect the declined reduced glutathione (GSH) content due to I/R insult. Worth mentioning is that the activity of catalase (CAT) did not change in response to either I/R insult or drug treatment. In conclusion, CUR was found to protect rat forebrain against I/R insult. These protective effects may be attributed to its antioxidant properties and/or its inhibitory effects on xanthine dehydrogenase/xanthine oxidase (XD/XO) conversion and resultant O(2)*(-) production.
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PMID:Protective effects of curcumin against ischaemia/reperfusion insult in rat forebrain. 1222 Sep 71

The protective effect of Nardostachys jatamansi (NJ) on neurobehavioral activities, thiobarbituric acid reactive substance (TBARS), reduced glutathione (GSH), thiol group, catalase and sodium-potassium ATPase activities was studied in middle cerebral artery (MCA) occlusion model of acute cerebral ischemia in rats. The right MCA of male Wistar rats was occluded for 2 h using intraluminal 4-0 monofilament and reperfusion was allowed for 22 h. MCA occlusion caused significant depletion in the contents of glutathione and thiol group and a significant elevation in the level of TBARS. The activities of Na(+)K(+) ATPase and catalase were decreased significantly by MCA occlusion. The neurobehavioral activities (spontaneous motor activity and motor coordination) were also decreased significantly in MCA occlusion group. All the alternations induced by ischemia were significantly attenuated by 15 days pretreatment of NJ (250 mg/kg po) and correlated well with histopathology by decreasing the neuronal cell death following MCA occlusion and reperfusion. The study provides first evidence of effectiveness of NJ in focal ischemia most probably by virtue of its antioxidant property.
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PMID:Protective effect of Nardostachys jatamansi in rat cerebral ischemia. 1247 70

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

Free Zn(2+) is released in excess at excitatory synapses in pathological conditions including transient global and focal cerebral ischemia, which causes neuronal and glial cell death. In the current study, we explored the mechanism underlying Zn(2+)-induced cell death in primary cortical astroglial cultures. Chronic treatment with 30-35 microM Zn(2+) led to the death of 70-95% of astrocytes within 18 h, preceded by Zn(2+) influx. Extracellular glutathione (GSH; 100 microM) completely blocked the Zn(2+) influx and Zn(2+) toxicity. The Zn(2+) toxicity was also inhibited when intracellular GSH was increased. Conversely, it was aggravated when intracellular GSH was depleted by buthionine sulfoximine (BSO). Consistently, the level of cellular GSH was notably decreased with a concurrent increase in oxidized GSH in Zn(2+)-treated astrocytes. These results suggest that the disruption of proper maintenance of thiol homeostasis is a mechanism underlying Zn(2+) toxicity in primary cortical astrocytes.
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PMID:Extracellular and intracellular glutathione protects astrocytes from Zn2+-induced cell death. 1259 26

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


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