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

The effect of alpha-tocopherol (vitamin E) on ischemic neuronal damage was studied in the gerbil. The animals were subjected to 5 min of cerebral ischemia by bilateral common carotid artery occlusion. Immediately after ischemia, alpha-tocopherol at a dose of 50 or 100 mg/kg was administered intravenously. Morphological changes in the CA1 sector of the hippocampus were evaluated after 7 days of survival. alpha-Tocopherol prevented ischemia-induced neuronal death. The average density of CA1 pyramidal neurons (cells/mm, mean +/- S.E.M.) was 252 +/- 8 (n = 8) in the sham-operated group, 50 +/- 20 (n = 8) in the ischemia group, and 140 +/- 35 (n = 8) and 182 +/- 36 (n = 8) in the groups treated with alpha-tocopherol at the doses of 50 and 100 mg/kg, respectively. The results suggest that free radical scavenging action of alpha-tocopherol played an important role in preventing the neuronal death.
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PMID:Protective effect of alpha-tocopherol on ischemic neuronal damage in the gerbil hippocampus. 233 5

To verify the lipid peroxidation in the focal cerebral ischemia, the levels of alpha-tocopherol, ubiquinone and ascorbate were measured in the ischemic center in rats. The former two were endogeneous lipid soluble antioxidants and the last was a water soluble antioxidant. alpha-Tocopherol, reduced ubiquinone-9 and -10, and reduced ascorbate decreased to 79%, 73%, 66%, and 76% 0.5 hour after ischemia, respectively. alpha-Tocopherol decreased to 63% 6 hours after ischemia, and then reached a plateau, while reduced ubiquinones and reduced ascorbate declined further to 16% and 10% 12 hours after ischemia, respectively, and then reached plateau levels. These results suggest their functional and durational differences as antioxidants against lipid peroxidation in this ischemic model. Although the reciprocal increase in oxidized ubiquinones during ischemia was not observed, that in oxidized ascorbate was noted. The complementary antioxidant system between cytoplasmic and membranous components, the combination alpha-tocopherol/ascorbate, was estimated from the calculated consumption ratio of these antioxidants, assuming that the loss of these reduced antioxidants is due to neutralization of free radicals. This system was suggested to play an important role in an early ischemic period. Urate also markedly increased during ischemia. Therefore, xanthine oxidase activity was measured in rats both in normal brain and in ischemic brain induced by four-vessel occlusion method. In the control rat, the enzyme activity was 0.87 +/- 0.13 nmol/g wet brain/min at 25 degrees C (mean +/- S.D.): 92.4% was associated with the NAD-dependent dehydrogenase form and only 7.6% with the oxygen-dependent superoxide-producing oxidase form. However, the ratio of the latter form increased to 43.7% after 0.5 hour of global ischemia despite the same level in total xanthine oxidase activity. This result suggests the involvement of the oxygen free radicals generated from the xanthine oxidase pathway in the pathogenesis of the ischemic injury of the rat brain.
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PMID:[Lipid peroxidation and changes in xanthine oxidase in cerebral ischemia]. 280 15

This study reports the effects of subchronic administration of the iron chelator deferoxamine (4.2 mg/day by osmotic minipump for 6 days) and a diet deficient in Vitamin E (15% RDA for 60 days) on the isoelectric electroencephalographic responses associated with 15 minutes of global transient cerebral ischemia in rats. Brain levels of thiobarbiturate-reacting substance (TBARS), a measure of lipid peroxidation, were lower in deferoxamine-treated animals and higher in Vitamin E deficit animals suggesting the treatments altered free radical activity at the time of ischemia. During ischemia, all test animals were observed to lose the righting reflex and enter a quiescent state. Fifty percent of the animals in two control groups (N = 15 per group) demonstrated an isoelectric electroencephalographic pattern (defined as 10% or less of pre-ischemia total EEG power) with a mean onset of 5.44 minutes. One third of the animals treated with deferoxamine (N = 15) experienced an isoelectric encephalogram with a mean onset of 8.6 minutes and 73% of the Vitamin E-deficient group (N = 15) experienced an isoelectric EEG with a mean onset of 3.43 minutes. Following reperfusion, EEG patterns returned to power levels within 20% of pre-ischemia levels in all animals. Control animals obtained this EEG power level within 1.34 minutes, deferoxamine-treated animals within 1.25 minutes and animals provided a diet deficient in Vitamin E within 5.03 minutes. Compared to mean total EEG power prior to the onset of ischemia, mean total EEG power five days after reperfusion was reduced 14% in the control groups and 59% in the Vitamin E-deficient group and increased 123% in the deferoxamine group. Results are discussed in relation to the possible involvement of free radicals in the ischemic and postischemic process.
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PMID:Effects of deferoxamine and a diet deficient in vitamin E on isoelectric electroencephalographic responses associated with ischemia by the four vessel occlusion method. 764 24

alpha-Tocopherol (alpha-TC) is considered an important endogenous brain antioxidant. The utility of brain alpha-TC levels as an index of in vivo lipid peroxidation has recently been suggested. Therefore, we explored the significance of alpha-TC levels in brains to ischemic insults associated with global or focal cerebral ischemia. Four ischemic models were used and alpha-TC was measured by HPLC. Brain alpha-TC levels in gerbils exposed to 20 min bilateral carotid artery occlusion (CAO) and 60 min reperfusion was 10.8 +/- 2.1 micrograms/g (x +/- S.D., n = 6) vs. 10.8 +/- 1.8 micrograms/g (n = 6) in sham controls. In gerbils subjected to 3 h unilateral CAO and 2 h RP, a procedure marked by neurological abnormalities, brain alpha-TC levels of ischemic and non-ischemic hemispheres were essentially the same (10.7 +/- 1.6 vs. 10.1 +/- 1.4 micrograms/g, n = 4). In rats subjected to 80 min unilateral middle cerebral artery occlusion followed by 60 min reperfusion, or 6 h occlusion without reperfusion, the brain alpha-TC levels in ipsilateral ischemic and contralateral non-ischemic cortex were not different (12.1 +/- 1.2 vs. 11.9 +/- 2.6 micrograms/g or 12.2 +/- 1.6 vs. 13.4 +/- 1.2 micrograms/g, n = 4-8). Our results demonstrated that brain alpha-TC levels can not be used as index of ischemia/reperfusion related lipid peroxidation or tissue injury.
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PMID:Brain alpha-tocopherol levels are not altered following ischemia/reperfusion-induced cerebral injury in rats and gerbils. 851 30

Effects of chronic (14 day) pretreatment of timed-release of alpha-tocopherol (approximately 1.25-5 mg/day) on alcohol-induced venular cerebrovasospasm, microvessel rupture and micro-hemorrhaging was studied by direct, quantitative in-vivo high-resolution TV microscopy of the intact rat brain. Sham animals chronically treated with placebo exhibited concentration-dependent venular cerebrovasospasm, microvessel rupture and focal hemorrhages, irrespective of route (i.e. perivascular, systemic) of ethanol administration. alpha-Tocopherol pretreatment either prevented or ameliorated greatly the cerebrovasospasm and vascular damage induced by ethanol. These results suggest that alcohol-induced cerebral vascular and brain damage by reperfusion injury events triggers lipid peroxidation of vascular smooth muscle and endothelial cell membranes; these pro-oxidant events could play a crucial role in the pathogenesis of alcohol-induced cerebral ischemia and stroke.
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PMID:alpha-Tocopherol attenuates alcohol-induced cerebral vascular damage in rats: possible role of oxidants in alcohol brain pathology and stroke. 899 29

Cerebral ischemia followed by oxygen reperfusion induces apoptosis in hippocampal neurons in stroke-prone spontaneously hypertensive rats (SHRSP) but not in Wistar Kyoto rats (WKY). The overproduction of oxygen-free radicals that occurs in the tissues of SHRSP is implicated in reoxygenation injury after hypoxia. Antioxidants inhibit reoxygenation injury in hippocampal slices, and temporal cortices in Alzheimer's disease increase sensitivity to oxygen-free radicals. Because this sensitivity may contribute to the development of the disease, we have studied hypoxia and oxygen reperfusion using cortical neurons isolated from WKY and SHRSP (at 15 days of gestation). We have tried to determine whether cortical neurons are damaged under these conditions, and whether neurons from SHRSP are more vulnerable than those from WKY. We have tried also to verify whether neuronal damage is minimized by vitamin E using the following techniques: (a) Trypan blue staining, (b) in situ staining of apoptosis, (c) ultrastructural examination, and (d) measurement of lactic dehydrogenase (LDH) activity in the bathing medium. Furthermore, we have examined the mechanisms involved in the development of neuronal damage and have studied ways of minimizing it. We demonstrated that 36 hours of hypoxia significantly increased the rate of cell death in SHRSP (p < 0.01), although 12 to 24 hours of hypoxia did not increase cell death in either WKY or SHRSP. In addition, 6 to 36 hours of hypoxia and 1.5 to 5 hours of oxygen reperfusion heavily damaged cells of both WKY and SHRSP, and most became apoptotic or necrotic. In contrast, cells incubated with 50 to 300 microg/ml of vitamin E remained intact, although 10 to 20 microg/ml of vitamin E did not totally preserve the cells. Moreover, vitamin E protected the neurons from high concentrations of sodium nitroprusside (nitric oxide donor) in a dose-dependent manner. Vitamin E, when added to the cells, increased in concentration in a time-dependent manner over a 24-hour period and in a dose-dependent manner below 200 microg/ml, and it was detected mostly in the mitochondria. We also demonstrated that serial treatments with allopurinol (a xanthine oxidase inhibitor) or superoxide dismutase preserved neurons during hypoxia and oxygen reperfusion. These data indicate that SHRSP neurons are weaker than WKY neurons in long-term hypoxia; oxygen radical generation occurs in the early minutes after reperfusion, and then the oxygen-free radicals cause heavy damage to the cells; and antioxidants including vitamin E react with the radicals, thereby preventing apoptosis and necrosis. Therefore, antioxidants appear to be the most important agents in lowering oxygen-free radical damage in cortical neurons.
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PMID:Vitamin E prevents apoptosis in cortical neurons during hypoxia and oxygen reperfusion. 984 Jun 16

Cerebral ischemia followed by oxygen reperfusion induced apoptosis in hippocampal neurons in stroke-prone spontaneously hypertensive rats (SHRSP) but not in Wistar Kyoto rats. Oxygen radicals were involved in reoxygenation injury after hypoxia in hippocampal slices. Vitamin E inhibited the reoxygenation injury in cultured cortical neurons. In addition, the temporal cortices in Alzheimer's disease have increased sensitivity to oxygen radicals, and Vitamin E slowed the progression of the disease. Thus we fed Wistar Kyoto and SHRSP rats either a normal diet or a high Vitamin E diet for 3 weeks. We measured Vitamin E concentrations of plasma and brain by applying the HPLC method. Vitamin E increased its concentration in plasma, cerebral cortex, and hippocampus (p < 0.01) during a 3-week pretreatment. In addition, we clipped both common carotid arteries in these rats for 30 minutes. After the blocking, the rats were reperfused for 6 and 9 days, respectively, and then killed. We cut the brains coronally, removed the hippocampal CA1 regions, and examined the neurons using an electron microscope. SHRSP rats with normal cerebral circulation had 30.4+/-8.0 apoptotic neurons per 1000 neurons. Cerebral ischemia followed by 6 and 9 days of reperfusion, respectively, increased apoptotic neurons in SHRSP rats fed a normal diet (6 days: 542.5+/-154.1 per 1000 neurons; 9 days: 657.5+/-110.2 per 1000 neurons). In contrast, apoptotic neurons in SHRSP rats fed a high Vitamin E diet were significantly (p < 0.01) small in number (6 days: 41.3+/-27.5 per 1000 neurons; 9 days: 35.5+/-19.7 per 1000 neurons) even though the rats were treated in the same way. These data demonstrate that oxygen radical generation occurs after reperfusion and that free radicals heavily damage the neurons in SHRSP rats. Vitamin E reacts with the radicals and prevents neuronal apoptosis caused by cerebral ischemia and reperfusion. Therefore, Vitamin E seems to be an important agent in lowering radical damage to hippocampal neurons.
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PMID:Vitamin E prevents apoptosis in hippocampal neurons caused by cerebral ischemia and reperfusion in stroke-prone spontaneously hypertensive rats. 1033 72

Vitamin E has been shown to have protective effects against cerebral ischemia, possibly due to its anti-oxidant effects. However, its non-anti-oxidant, intracellular molecular mechanism remains elusive. For in vivo experiments in rats, orally administered vitamin E significantly reduced not only the brain infarct volume but also space navigation disability after permanent middle cerebral artery (MCA) occlusion. The level of anti-oxidant after MCA occlusion was significantly increased specifically in the ipsilateral brain tissues of vitamin E-treated rats. For in vitro experiments, posttreatment with vitamin E protected primary cultured neurons from nitric oxide-induced insult. Vitamin E induced the expression of the alpha subunit of hypoxia-inducible factor-1 (HIF-1) and its target genes, including vascular endothelial growth factor (VEGF) and heme oxygenase-1. The hypoxia response element on the VEGF promoter was responsible for this vitamin E-induced transcriptional activation of VEGF gene. Taken together, these results suggest that cerebral infarction increased the permeability of vitamin E across the blood-brain barrier, and this increased vitamin E in brain tissue elicited neuroprotective effects not only through scavenging oxidants, as are previously well reported, but also by transactivating HIF-1-dependent genes, which results in protection of brains from ischemic insults.
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PMID:Protective effect of vitamin E against focal brain ischemia and neuronal death through induction of target genes of hypoxia-inducible factor-1. 1520 61

Oxidative stress is implicated in the pathogenesis of ischemic brain injury. Flavonoids from various herbal extracts have been shown to be neuroprotective in experimental models of cerebral ischemia/reperfusion (I/R). The present study was designed to investigate the neuroprotective effect of the biflavone rich fraction from Araucaria bidwillii Hook (ABH) (Family: Araucariaceae) in I/R induced oxidative stress. The I/R was induced by occluding bilateral common carotid arteries (BCCAO) for 30 min, followed by 24 h reperfusion. BCCAO caused significant depletion in superoxide dismutase (SOD), catalase (CAT), glutathione (GSH) and significant increase in lipid peroxidation (LPO) in various brain regions. The neurological deficit and sensory motor function were also decreased significantly by BCCAO group as compared to sham group animals. All the alteration induced by cerebral ischemia was significantly attenuated by 7 days' pretreatment with biflavone fraction (BFR) at the dose of 100 and 200 mg/kg, comparable to that given by Vitamin E (200 mg/kg). Consistent with neurobehavioral deficits, pretreatment with biflavones at higher doses significantly reduced ischemia-induced neuronal loss of the brain. In conclusion the biflavone rich fraction from A. bidwillii was found to protect rat brain against I/R induced oxidative stress, and attributable to its antioxidant properties.
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PMID:Protective effect of biflavones from Araucaria bidwillii Hook in rat cerebral ischemia/reperfusion induced oxidative stress. 1725 Sep 3

The membrane, antioxidant and functional effects of vinpocetine and a-tocopherol have been investigated under conditions of acute experimental cerebral ischemia in rats. Vinpocetine administration decreased accumulation of lysophospholipids in brain plasma membranes. Vinpocetine also blocked accumulation of conjugated dienes (CD). alpha-Tocopherol inhibited augmentation in CD content and did not reduce the level of lysophospholipids in brain plasma membranes. Functional consequences of membrane impairments were also detected in some behavioral tests and physical capabilities. Administration of both vinpocetine and alpha-tocopherol decreased manifestations of the altered parameters induced by cerebral ischemia and vinpocetine was more effective than alpha-tocopherol.
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PMID:[Membrane and functional effects of vinpocetine and tocopherol in rats with experimental cerebral ischemia]. 2001 94


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