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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We previously showed that sunlight-mimicking light induces genotoxic damage not only in skin but also even in lung, bone marrow, and peripheral blood of hairless mice. Moreover, light and smoke acted synergically in the respiratory tract. To clarify the mechanisms involved, we investigated by cDNA-arrays the expression of 746 toxicologically relevant genes in skin and lungs of mice exposed for 28 days to light and/or environmental cigarette smoke. Glutathione-S-transferase-Pi and catalase were overexpressed in the lungs of mice exposed to light only. Moreover, the light induced in skin the expression of genes involved in carcinogenesis, photoaging, and production of genotoxic and oxidizing derivatives traveling at a distance. Smoke induced the expression of multiple genes in both skin and lung, which reflect adaptive responses and mechanisms related to cancer and, possibly, to emphysema and stroke. As shown in mice exposed to both light and smoke, the light tended to increase smoke-induced gene expression in lungs, while smoke tended to attenuate light-induced gene expression in skin. The oral administration of the nonsteroidal anti-inflammatory drug sulindac inhibited the light-induced overexpression of cyclooxygenase-2 and oxidative stress-related genes in skin, and down-regulated smoke-induced genes involved in oxidative stress, removal of damaged proteins, inflammation, and immune response in lung. These results provide a mechanistic insight explaining the systemic alterations induced by both light and smoke in mouse skin and lungs.
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PMID:Alterations of gene expression in skin and lung of mice exposed to light and cigarette smoke. 1528 47

Ascorbic acid (AA) is a well-known antioxidant. It also has pro-oxidant effects, however, in the presence of free transition metals. Because of the pro-oxidant effects of AA, dehydroascorbic acid (DHA), an oxidized form of AA, has been used as a substitute for AA. DHA has been shown recently to have a protective effect in an experimental stroke model. This study was carried out to determine if DHA has different effects from AA on hydrogen peroxide (H2O2)-induced oxidative cell death in primary astrocytes. DHA was found to prevent cell death and reverse mitochondrial dysfunction after exposure to H2O2. DHA significantly increased the glutathione peroxidase (GPx) and glutathione reductase (GR) activities 1 hr after H2O2 exposure. Moreover, DHA not only reversed the decrease in the glutathione (GSH) levels, but also significantly enhanced it by stimulating the pentose phosphate pathway (PPP) 15 hr after H2O2 exposure. DHA also reduced production of reactive oxygen species (ROS) after H2O2 exposure. In contrast, AA accelerated H2O2-induced cell death. To determine if the pro-oxidant effect of AA is related to iron, the effect of AA on cell death was examined using an iron chelator, desferrioxamine. Even though co-pretreatment with AA and desferrioxamine could abrogate the aggravating effects of AA on H2O2-induced cell death at early stages, it could not prevent H2O2-induced cell death over a 24-hr period. These results suggest that DHA has distinct effects from AA and prevent H2O2-induced cell death by increasing the GSH levels mediated by the GPx and GR activities and PPP.
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PMID:Dehydroascorbic acid prevents oxidative cell death through a glutathione pathway in primary astrocytes. 1566 57

Stroke causes brain injury in millions of people world wide each year. Despite the enormity of problem, currently there is no established therapy, which can restore the blood flow at infracted area and also improve the neurological deficit. The present study was carried out to investigate the effect of an endothelin antagonist (TAK-044) in middle cerebral artery (MCA) occlusion model of acute ischemic stroke in rats. Male Wistar rats were pretreated with TAK-044 (5 mg/kg, i.p.) for 7 days and thereafter subjected to focal ischemia by occlusion of MCA using intraluminal thread for two hours. 30 min after reperfusion the animals were subjected to diffusion-weighted imaging (DWI) for assessment of protective effect. Twenty-four hours later the motor performance was tested and subsequently the animals were sacrificed for estimation of markers of oxidative stress; malondialdehyde (MDA), glutathione (GSH) and superoxide dismutase (SOD). Control group received vehicle (saline) and similar experimental protocol was followed. In the TAK-044 pretreated group, percent hemispheric lesion area (% HLA) in DWI was significantly attenuated 17.5 +/- 0.5% as compared to control group 61.2 +/- 5.9%. Significant motor impairment, with significant elevated levels of MDA, decrease in GSH and SOD were observed in the vehicle treated MCA occluded rats. Pretreatment with TAK-044 prevented the motor impairment and significantly reversed the changes in markers of oxidative stress (MDA, GSH and SOD). In addition to well-known vasodilatory effect, TAK-044 has recently been documented to have antioxidant and anti-inflammatory properties. These effects can contribute to the protection afforded by TAK-044 in the present study.
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PMID:Effect of endothelin antagonist (TAK-044) on cerebral ischemic volume, oxidative stress markers and neurobehavioral parameters in the middle cerebral artery occlusion model of stroke in rats. 1584 15

Glutathione plays a critical role in many biological processes both directly as a co-factor in enzymatic reactions and indirectly as the major thiol-disulfide redox buffer in mammalian cells. Glutathione also provides a critical defense system for the protection of cells from many forms of stress. However, mild stress generally increases glutathione levels, often but not exclusively through effects on glutamate cysteine ligase, the rate-limiting enzyme for glutathione biosynthesis. This upregulation in glutathione provides protection from more severe stress and may be a critical feature of preconditioning and tolerance. In contrast, during aging, glutathione levels appear to decline in a number of tissues, thereby putting cells at increased risk of succumbing to stress. The evidence for such a decline is strongest in the brain where glutathione loss is implicated in both Parkinson's disease and in neuronal injury following stroke.
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PMID:The effects of stress and aging on glutathione metabolism. 1593 51

Korean ginseng tea (KGT), prepared from the roots of Panax ginseng, is widely used by Korean people for antistress, antifatigue, and endurance promoting effects. In the present study we evaluated neuroprotective/cerebroprotective actions of KGT in stroke, using rat global and focal models of ischemia. Varied biochemical/enzymatic alterations, produced subsequent to the application of middle cerebral artery (MCAO) and bilateral carotid artery occlusion (BCAO) followed by reperfusion viz. increase in lipid peroxidation (LPO) and decrease in glutathione (GSH), glutathione reductase (GR), catalase (CAT), glutathione-S-transferase (GST), glutathione peroxidase (GPx) and superoxide dismutase (SOD), were markedly reversed and restored to near normal levels in the groups pre-treated with KGT (350 mg/kg given orally for 10 days). It is concluded that the protective action, exhibited by KGT against hypoperfusion/reperfusion induced brain injury, suggests its therapeutic potential in cerebrovascular diseases (CVD) including stroke. These findings are important because: (a) the present treatment strategies for CVD are far from adequate and (b) KGT with wide usage is known to be a safe natural product.
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PMID:Cerebroprotective effect of Korean ginseng tea against global and focal models of ischemia in rats. 1597 Apr 12

We investigated whether protein-energy malnutrition (PEM) exacerbates brain injury in global ischemia. It was hypothesized that PEM would increase secondary brain damage by worsening ischemia-induced depletion of glutathione (GSH) and increasing oxidative stress. Adult male gerbils were fed an adequate protein (12.5%; C) or low protein (2%; PEM) diet for 4 weeks and subjected to 5 min of bilateral carotid artery occlusion (Ischemia) or sham surgery (Sham). At 12 h post-ischemia, GSH and markers of oxidative stress were measured in hippocampus and neocortex. The remaining gerbils were tested in the open field on days 3, 7, and 10, with viable hippocampal CA1 neurons assessed on day 10. Although the habituation of C-Ischemia gerbils in the open field was normal by day 7, PEM-Ischemia gerbils failed to habituate even by day 10 and spent greater time in the outer zone (P < 0.05). Mean (+/-SEM) total number of viable CA1 neurons at 10 days post-ischemia were C-Sham = 713 (13), C-Ischemia = 264 (48), PEM-Sham = 716 (12), and PEM-Ischemia = 286 (66). Although PEM did not increase CA1 neuron loss caused by ischemia, a subset (4/12) of PEM-Ischemia gerbils showed dramatic reactive gliosis accompanied by extensive neuronal loss. Hippocampal protein thiols were decreased by PEM and ischemia. Although the mechanism is yet to be established, the finding that PEM worsens functional outcome following global ischemia is clinically relevant since 16% of elderly are nutritionally compromised at the time of admission for stroke.
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PMID:Protein-energy malnutrition impairs functional outcome in global ischemia. 1617 6

The levels of oxidants xanthine oxidase (XO), nitric oxide (NO), and malondialdehyde (MDA) and of the antioxidant enzymes superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and glutathione reductase (GRD) were determined in plasma within 24 h after onset of hemorrhagic stroke in 17 patients (9 men and 8 women, aged 60.7+/-11.5 yr) and in 20 healthy controls (12 men and 8 women, aged 62.5+/-8.3 yr). Compared to controls, the plasma SOD and total superoxide scavenger activities (TSSA) were significantly lower and the NO levels were significantly higher among the stroke patients. XO showed a slight, nonsignificant increase in the patients, but the levels of MDA, NSSA, GRD, and GSH-Px did not show any significant differences between the two groups. The hemorrhage volume was negatively correlated with the initial score of the Glasgow Coma Scale and a positive correlation with lethal outcome, but it did not correlate significantly with any of the measured parameters. The results suggest that free radicals might play a role in the development of brain injury following brain hemorrhage.
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PMID:Plasma values of oxidants and antioxidants in acute brain hemorrhage: role of free radicals in the development of brain injury. 1632 58

Epidemiological studies indicate that the intake of flavonoids is inversely associated with risk of stroke, cardiovascular diseases and cancer. Isoliquiritigenin (ISL), a flavonoid constituent in the root of Glycyrrhiza glabra, is known to have vasorelaxant effect, antioxidant, anti-platelet, anti-tumor, anti-allergic, antiviral activities and estrogenic properties. However, there is no report on the effects of ISL in cerebral ischemia. Evidence demonstrate that the impaired energy metabolism and the excessive generation of reactive oxygen radicals (ROS) contribute to the brain injury associated with cerebral ischemia. In the present study, the protective effects of ISL were investigated in transient middle cerebral artery occlusion (MCAO)-induced focal cerebral ischemia-reperfusion injury in rats. Male Sprague-Dawley rats were divided into five groups: sham-operated group, vehicle-pretreated group, and three ISL-pretreated groups (5, 10 and 20 mg kg(-1), i.g.). ISL were administered once a day, for 7 days prior to ischemia. The rats were subjected to 2 h right MCAO via the intraluminal filament technique and 22 h reperfusion. Pretreatment with ISL significantly reduced the cerebral infarct volume and edema and produced significant reduction in neurological deficits. In this study, in order to clarify the mechanism of ISL's protection against cerebral ischemia damage, cerebral energy metabolism, brain Na+K+ATPase activity, malondialdehyde (MDA) content and antioxidant enzyme activities were measured. ISL pretreatment increased the brain ATP content, energy charge (EC) and total adenine nucleotides (TAN) in a dose-dependent manner. The brain Na+K+ATPase activity was protected significantly by pretreatment of ISL for 7 days. Pretreatment with ISL significantly inhibited the increases of brain MDA content and prevented the activities of brain superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) from declines caused by cerebral ischemia-reperfusion. All these findings indicate that ISL has the protective potential against cerebral ischemia injury and its protective effects may be due to the amelioration of cerebral energy metabolism and its antioxidant property.
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PMID:Protective effects of isoliquiritigenin in transient middle cerebral artery occlusion-induced focal cerebral ischemia in rats. 1645 97

The efficacy of nitric oxide (NO) treatment in ischemic stroke, though well recognized, is yet to be tested in clinic. NO donors used to treat ischemic injury are structurally diverse compounds. We have shown that treatment of S-nitrosoglutathione (GSNO) protects the brain against injury and inflammation in rats after experimental stroke [M. Khan, B. Sekhon, S. Giri, M. Jatana, A. G. Gilg, K. Ayasolla, C. Elango, A. K. Singh, I. Singh, S-Nitrosoglutathione reduces inflammation and protects brain against focal cerebral ischemia in a rat model of experimental stroke, J. Cereb. Blood Flow Metab. 25 (2005) 177-192.]. In this study, we tested structurally different NO donors including GSNO, S-nitroso-N-acetyl-penicillamine (SNAP), sodium nitroprusside (SNP), methylamine hexamethylene methylamine NONOate (MAHMA), propylamine propylamine NONOate (PAPA), 3-morpholinosydnonimine (SIN-1) and compared their neuroprotective efficacy and antioxidant property in rats after ischemia/reperfusion (I/R). GSNO, in addition to neuroprotection, decreased nitrotyrosine formation and lipid peroxidation in blood and increased the ratio of reduced versus oxidized glutathione (GSH/GSSG) in brain as compared to untreated animals. GSNO also prevented the I/R-induced increase in mRNA expression of ICAM-1 and E-Selectin. SNAP and SNP extended limited neuroprotection, reduced nitrotyrosine formation in blood and blocked increase in mRNA expression of ICAM-1 and E-Selectin in brain tissue. PAPA, MAHMA, and SIN-1 neither protected the brain nor reduced oxidative stress. We conclude that neuroprotective action of NO donors in experimental stroke depends on their ability to reduce oxidative stress both in brain and blood.
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PMID:Cerebrovascular protection by various nitric oxide donors in rats after experimental stroke. 1652 50

As part of a basic study on the prevention of cerebral injury, ajoene (0.5 mg/d) and oil-macerated garlic extract (OMGE, containing 0.5 mg ajoene/d) were administrated to stroke-prone spontaneously hypertensive rats (SHRSP) among 8 weeks from 9 weeks of age. In the control group, 3 of 10 rats died (30%), whereas all SHRSP treated by ajoene or OMGE survived. Our results suggested that ajoene and OMGE-treatment reduced the mortality and cerebral injury in SHRSP. The levels of thiobarbituric acid reactive substance (TBARS) and the enzymatic activities of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and catalase (CAT) in the serum of stroke stage of SHRSP were measured. The results obtained were as follows; the TBARS level of the ajoene and OMGE-treated groups were lower than those of control groups. On the other hand, the GSH-Px and SOD activities of the ajoene and OMGE-treated groups were higher. Our results suggested that ajoene and OMGE were capable of having prophylactic effects on cerebral injury in SHRSP.
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PMID:Prophylactic effects of ajoene on cerebral injury in stroke-prone spontaneously hypertensive rats (SHRSP). 1659 90


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