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

Oxidative stress plays an important role in neuronal cell death associated with many different neurodegenerative conditions such as cerebral ischemia and Parkinson's disease. Elevated levels of glutamate are thought to be responsible for CNS disorders through various mechanisms causing oxidative stress induced by a nonreceptor-mediated oxidative pathway which blocks cystine uptake and results in depletion of intracellular glutathione (GSH). The newly designed amide form of N-acetylcysteine (NAC), N-acetylcysteine amide (NACA), was assessed for its ability to protect PC12 cells against oxidative toxicity induced by glutamate. NACA was shown to protect PC12 cells from glutamate (Glu) toxicity, as evaluated by LDH and MTS assays. NACA prevented glutamate-induced intracellular GSH loss. In addition, NACA restored GSH synthesis in a Glu (10 mM) plus buthionine-sulfoximine (BSO) (0.2 mM)-treated group, indicating that the intracellular GSH increase is independent of gamma-GSC (gamma-glutamylcysteinyl synthetase). The increase in levels of reactive oxygen species (ROS) induced by glutamate was significantly decreased by NACA. Measurement of malondialdehyde (MDA) showed that NACA reduced glutamate-induced elevations in levels of lipid peroxidation by-products. These results demonstrate that NACA can protect PC12 cells against glutamate cytotoxicity by inhibiting lipid peroxidation, and scavenging ROS, thus preserving intracellular GSH.
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PMID:Effects of N-acetylcysteine amide (NACA), a novel thiol antioxidant against glutamate-induced cytotoxicity in neuronal cell line PC12. 1612 Apr 36

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

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 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

Studies have shown that ebselen is an antiinflammatory and antioxidative agent. Its protective effect has been investigated in oxidative stress related diseases such as cerebral ischemia in recent years. However, experimental evidence also shows that ebselen causes cell death in several different cell types. Whether ebselen will have a beneficial or detrimental effect on cells under ischemic condition is not known. Herein, we studied the effect of ebselen on C6 glioma cells under oxygen and glucose deprivation (OGD), an in vitro ischemic model. We found that ebselen significantly enhanced cell death after 3 h of OGD as observed by lactase dehydrogenase (LDH) release and cellular morphological changes. Further studies revealed that depletion of cellular glutathione level by the combined action of ebselen and OGD played a role in enhanced cell death as demonstrated by the following evidence: (1) cellular GSH was significantly depleted by the combined effort of ebselen and OGD, compared to that of ebselen or OGD insult alone; (2) exogenous addition of N-acetyl cysteine completely diminished the cell damage induced by ebselen and OGD; (3) supplement of glucose, which provides cellular reducing agents and thus maintains cellular GSH level, to the OGD medium diminished C6 cell damage induced by ebselen. We conclude that depleting cellular glutathione plays an important role in ebselen-induced cell death with OGD. Our results suggest that ebselen can have a beneficial or toxic effect, depending on the availability of GSH.
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PMID:Ebselen induced C6 glioma cell death in oxygen and glucose deprivation. 1669 67

Radix Angelica sinensis, known as Danggui in Chinese, has been used to treat cardiovascular and cerebrovascular diseases in Traditional Chinese Medicine for a long time. Modern phytochemical studies showed that Z-ligustilide (LIG) is the main lipophilic component of Danggui. In this study, we examined whether LIG could protect ischemia/reperfusion-induced brain injury by minimizing oxidative stress and anti-apoptosis. Transient forebrain cerebral ischemia (FCI) was induced by the bilateral common carotid arteries occlusion for 30 min. LIG was intraperitoneally injected to ICR mice at the beginning of reperfusion. As determined via 2,3,5-triphenyl tetrazolium chloride (TTC) staining at 24 h following ischemia, the infarction volume in the FCI mice treated without LIG (22.1 +/- 2.6%) was significantly higher than that in the FCI mice treated with 5 mg/kg (11.8 +/- 5.2%) and 20 mg/kg (2.60 +/- 1.5%) LIG (P < 0.05 or P < 0.01). LIG treatment significantly decreased the level of malondialdehyde (MDA) and increased the activities of the antioxidant enzyme glutathione peroxidase (GSH-PX) and superoxide dismutase (SOD) in the ischemic brain tissues (P < 0.05 or P < 0.01 vs. FCI group). In addition, LIG provided a great increase in Bcl-2 expression as well as a significant decrease in Bax and caspase-3 immunoreactivities in the ischemic cortex. The findings demonstrated that LIG could significantly protect the brain from damage induced by transient forebrain cerebral ischemia. The antioxidant and anti-apoptotic properties of LIG may contribute to the neuroprotective potential of LIG in cerebral ischemic damage.
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PMID:Neuroprotective role of Z-ligustilide against forebrain ischemic injury in ICR mice. 1680 12

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

Oxidative stress may be regarded as an imbalance between free radical production and opposing antioxidant defenses. Free radical oxidative stress is implicated in rat cerebral ischemia and naturaceutical antioxidants are dietary supplements that have been reported to have neuroprotective activity. Many studies have reported dietary sesame oil (SO) as an effective antioxidant. In the present study the neuroprotective effect of dietary SO was evaluated against middle cerebral artery occlusion (MCAO)-induced cerebral ischemia injury in rats. Rats were fed on diet (20% SO) for 15 days. The middle cerebral artery of adult male Wistar rat was occluded for 2 h and reperfused for 22 h. The antioxidant properties of brain were measured as levels of reduced glutathione (GSH), glutathione-S-transferase (GST), glutathione peroxide (GPx), glutathione reductase (GR), catalase (CAT), superoxide dismutase (SOD) and thiobarbituric acid reactive substance (TBARS). A decrease in the activity of all the enzymatic and non-enzymatic antioxidants was observed along with an increase in lipid peroxidation (LPO) in MCAO group. The neurobehavioral activity of rats was also observed by using videopath analyzer. Dietary SO improved the antioxidant status in MCAO+SO group when compared with MCAO group. The results of neurobehavioral activity also support our biochemical data. The results obtained suggest protective effect of SO against cerebral ischemia in rat brain through their antioxidant properties.
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PMID:Effect of dietary sesame oil as antioxidant on brain hippocampus of rat in focal cerebral ischemia. 1682 28

Increasing evidence demonstrates that oxidative stress plays an important role in brain injury in experimental models of brain ischemia. Thymoquinone, the main constituents of the volatile oil from Negella sativa seeds, is reported to possess strong antioxidant properties. Hence, the present study was undertaken to evaluate the neuroprotective effect of thymoquinone against transient forebrain ischemia-induced neuronal damage in the rat hippocampus. Rats were divided randomly into five groups: control, sham, ischemia, thymoquinone and ischemia+thymoquinone. Transient forebrain ischemia was induced with bilateral occlusion of both common carotid arteries for 10 min followed by 7 days of reperfusion. Thymoquinone was administered (5 mg/kg/day p.o.) 5 days before ischemia and continued during the reperfusion time. Animals were sacrificed, and brain tissues were isolated for histopathological examination. Hippocampal tissues were also used for determination of malondialdehyde levels, an end product of lipid peroxidation; glutathione (GSH) levels, a key antioxidant and the activities of the antioxidant enzymes catalase and superoxide dismutase (SOD). Thymoquinone and its metabolite thymohydroquinone were tested as inhibitors of the in vitro non-enzymatic lipid peroxidation induced by iron-ascorbate in the hippocampal homogenate. Forebrain ischemia-reperfusion neural injury in rats was demonstrated by histopathological observation, which revealed significant neural cell death in the hippocampus CA1 area 7 days post-ischemia (77% cell loss). Additionally, forebrain ischemia-reperfusion oxidative injury in rats was demonstrated by a significant increase in malondialdehyde and a significant decrease in GSH contents, catalase and SOD activities in the hippocampal tissue compared to the control or sham-operated groups. Pretreatment of thymoquinone attenuated forebrain ischemia-induced neuronal damage manifested by significantly decreasing the number of dead hippocampal neuronal cells (24% in thymoquinone-treated versus 77% for ischemia, P<0.001), which confirm the protective role of thymoquinone in ischemia-reperfusion injury. Also, pretreatment of ischemic rats with thymoquinone decreased the elevated levels of malondialdehyde and increased GSH contents, catalase and SOD activities to normal levels. Thymoquinone and thymohydroquinone inhibited the in vitro non-enzymatic lipid peroxidation in hippocampal homogenate induced by iron-ascorbate. The IC50 for thymoquinone and thymohydroquinone were found to be 12 and 3 microM respectively. This suggests that the protection of thymoquinone and its metabolite involve increased resistance to oxidative stress. In conclusion, thymoquinone is effective in protecting rats against transient forebrain ischemia-induced damage in the rat hippocampus. This spectacular protection makes thymoquinone a promising agent in pathologies implicating neurodegenaration such as cerebral ischemia.
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PMID:Neuroprotective effects of thymoquinone against transient forebrain ischemia in the rat hippocampus. 1682 80

To investigate the protective effect of ginsenoside Re (Re) against cerebral ischemia-reperfusion injury, adult male Wistar rats weighing 250-300 g were subjected to either sham surgery or middle cerebral artery occlusion (MCAO) for 2 h of brain ischemia and 2 h reperfusion. A fluorescence polarization assay was carried out for membrane fluidity of brain mitochondria. Lipid peroxidation [malondiadehyde (MDA) formation], superoxide dismutase (SOD) and glutathion peroxidase (GSH-Px) of rat brain were estimated by fluorometric methods. It was observed that Re (5, 10, 20 mg kg-1 p.o. pretreatment for 7 d, once a day) significantly improved the fluidity of mitochondrial membranes as demonstrated by a reduction of average microviscosity, ameliorated lipid peroxidation by raising the activities of SOD and GSH-Px, and reduced the content of MDA in rat brain. This study demonstrated a direct protective effect of Re against cerebral ischemia-reperfusion injury.
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PMID:Protective effect of ginsenoside-Re against cerebral ischemia/reperfusion damage in rats. 1714 90


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