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

Formation of free radicals and subsequent lipid peroxidation may have an important role in tissue injury and neuronal cell death after cerebral ischaemia. We conducted a prospective, controlled study to determine whether the endogenous antioxidant vitamins A and E had a protective function in acute ischaemic stroke. The study population consisted of 80 patients seen at the Free University Hospital in Brussels. Entry criteria were occurrence of sudden focal neurological deficit lasting more than 3 h; deficit due to acute ischaemia in the territory of the middle cerebral artery; and investigation within 24 h of onset of the episode. Outcome was assessed within the first 21 days. 80 controls matched for age and sex had various neurological disorders other than acute ischaemia. Serum concentrations of vitamins A and E were similar in the study and control groups. In the study population a serum vitamin A concentration higher than the mean of 2.27 mumol/l was associated with a higher frequency of complete recovery within the first 24 h (p less than 0.05), decreased mortality (p = 0.038), and a better outcome as assessed by the Mathew scale of neurological deficit (p less than 0.03) and the Barthel index. There was no significant difference in outcome between patients with vitamin E concentrations above or below the mean of 35.3 mumol/l. Our results suggest a beneficial effect of a high serum vitamin A concentration on early outcome in ischaemic stroke.
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PMID:Serum concentrations of vitamins A and E and early outcome after ischaemic stroke. 135 49

The ability of stobadine (ST) to prevent lipid peroxidation was tested in incomplete rat cerebral ischemia induced by 4 hour ligation of the common carotid arteries with a subsequent 10 min reperfusion. The extent of lipid peroxidation was determined by the measurement of the level of conjugated dienes (CD) and thiobarbituric acid reactive substances (TBARS). The levels of CD and TBARS were significantly elevated in brain cortex samples from animals subjected to ischemia followed by reoxygenation in comparison with ischemic samples without reperfusion, samples from sham operated or control animals. The concentration of CD and TBARS significantly decreased in animals treated with therapeutic doses of ST (2 mg/kg) administered i.v. immediately before reperfusion or 10 min after the onset of reperfusion. Stobadine was more effective than the known lipid antioxidant vitamin E, given in a dose of 30 mg/kg.day i.m. over 3 consecutive days prior to ischemia. The beneficial effect of ST on survival of rats was more effective in comparison with vitamin E. Significant changes were found in the activities of the antioxidative enzymes, i.e. increase in superoxide dismutase (SOD) and decrease in glutathione peroxidase (GP) in brain cortex samples from animals subjected to ischemia followed by reoxygenation. Stobadine prevented these changes. Catalase (CAT) activity was not detectable. It may be concluded from the increased SOD activity that oxygen radicals play a significant role in cerebral ischemia followed reperfusion. In addition to its antioxidant effect, stobadine probably prevents superoxide radical generation. The mechanism of xanthine oxidase inhibition is not involved in preventing superoxide radical generation by stobadine. Stobadine maintained high GP activity, probably by preventing glutathione oxidation.
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PMID:Effect of stobadine on brain lipid peroxidation induced by incomplete ischemia and subsequent reperfusion. 178 73

We examined the 21-aminosteroid U74006F, a potent inhibitor of lipid peroxidation, for potential neuroprotective effects in a canine model of complete cerebral ischemia. Two 1.5-mg/kg boluses were administered to six dogs, the first bolus 15 minutes prior to a 12-minute episode of complete cerebral ischemia and the second bolus after 11 minutes of ischemia, 1 minute prior to reperfusion. Using this dosage regimen, plasma U74006F levels of greater than 0.3 microgram/ml were maintained for up to an hour postischemia. An additional six animals received equal volumes of the citrate vehicle solution. At 24 and 48 hours postischemia, the dogs were neurologically evaluated by an observer blinded as to treatment selection. All six U74006F-treated animals had a normal neurologic outcome at 48 hours postischemia, while the citrate vehicle-treated animals all suffered moderate to severe neurologic deficits. The difference in outcome was significant at both 24 and 48 hours (p less than 0.005). Although U74006F is a 21-aminosteroid, it is not reported to possess glucocorticoid activity. This is supported by the present finding that no changes in plasma glucose concentration were observed following administration of the drug. The systemic vitamin E levels of citrate vehicle-treated animals decreased significantly (from 4.10 +/- 0.46 micrograms/ml to 2.95 +/- 0.38 micrograms/ml, p less than 0.05), whereas the vitamin E levels in U74006F-treated animals did not decrease significantly. These results suggest that U74006F may be of benefit in improving neurologic outcome when administered prior to an episode of complete cerebral ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pretreatment with U74006F improves neurologic outcome following complete cerebral ischemia in dogs. 185 10

Opiate-receptor antagonists improve behavioral, electrophysiologic and/or histologic outcome in various experimental models of central nervous system ischemia. To address the potential mechanism(s) by which opiate-receptor antagonists may exert their protective actions in cerebral ischemia, metabolic and biochemical changes were measured in brain of rats pretreated with the opiate-receptor antagonist nalmefene or vehicle and subjected to 60 min of global ischemia followed by 2 hr of reperfusion. 31P and 1H magnetic resonance spectroscopy were used to follow the metabolic changes during ischemia and reperfusion, after which brain tissue was frozen in situ. Biochemical assays included free fatty acids, thromboxane B2, ascorbate, vitamin E and amino acids. Nalmefene-treated animals showed more rapid and complete recovery of cellular bioenergetic state (as indicated by the phosphocreatine to inorganic phosphate ratio), tissue acidosis and lactate levels during reperfusion than placebotreated controls. Ischemia/reperfusion caused significant increases of fatty free acids and thromboxane, associated with significant decreases of ascorbate and glutamate; nalmefene pretreatment limited each of these changes. The degree of metabolic improvement as reflected by recovery of high energy phosphates and reduction of lactic acidosis were highly correlated with changes in tissue levels of arachidonate and glutamate. Thus, the beneficial effects of opiate-receptor antagonists in cerebral ischemia may be due, in part, to an ability to enhance metabolic recovery with associated, reduction in phospholipid hydrolysis and excitotoxin release.
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PMID:Opiate-receptor antagonist improves metabolic recovery and limits neurochemical alterations associated with reperfusion after global brain ischemia in rats. 224 36

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 evaluate the scavenging effect of mannitol, vitamin E and betamethasone in cerebral ischemia, spin trapping technique was applied to the detection of the free radicals generated in ischemic brain homogenate. Thirty Wistar rats were used for this study. In the control group, the brain homogenate prepared immediately after decapitation was preserved at 37 degrees C under N2 gas. Before the preservation and at 30 min, 60 min and 120 min from the start of the preservation, two reaction mixtures containing of spin trapping reagent phenyl-t-butyl nitrone (PBN), NADPH, Fe-EDTA and brain homogenate was prepared from each brain sample--one to be incubated for 20 min at 37 degrees C in air and one to be incubated in nitrogen gas under similar condition. Then the free radical adducts of PBN were measured by electron spin resonance (ESR). In pre-treated group, mannitol, vitamin E and betamethasone were administered intravenously 30 min prior to the decapitation and spin adducts of PBN were detected by same procedures as in control group. The ESR spectra, which hyperfine coupling constants were AN = 16.0-16.6 G and AH beta = 3.0-3.8 G, were obtained from the reaction mixtures in each group. Analyses of their relative intensity in control group revealed that the formation of free radical adducts of PBN was increased dependent on the preservation period under aerobic incubation, and increased gradually for 60 min of preservation time followed by a decrease under anaerobic incubation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Protective effect of radical scavengers on cerebral infarction--experimental study utilizing the spin trapping method of ESR]. 299 96

Phenytoin is well known as the anticonvulsant agent and also said to protect the brain against ischemic damage. The purpose of the present experiment is to study the therapeutic effect of phenytoin on cerebral ischemia and confirm whether the effectiveness of phenytoin could be enhanced by combination of free radical scavengers such as mannitol and vitamin E. In this experiment, twenty-five dogs were subjected to ischemia, using the "canine model of complete ischemic brain regulated with a perfusion method" in which it is possible to control the degree of blood flow to a cerebral hemisphere via a perfusion pump at will. Five animals served as untreated control, fifteen received treatment with phenytoin (7 mg/kg in five dogs, 10 mg/kg in five dogs and 30 mg/kg in five dogs) and five treated with 10 mg/kg phenytoin, 2 g/kg of mannitol and 30 mg/kg of vitamin E. These drugs were administered intravenously 20 minutes prior to the production of ischemia, when cerebral blood flow was reduced to one-tenth its normal volume. After one hour, cerebral blood flow was restored and the recovery of electrical activity of the brain and the degree of brain swelling were observed for three hours. With regard to the recovery of EEG, no recovery of EEG was seen subsequent to recirculation except one dog in the control group. Whereas in the group treated with phenytoin, gradual emergence of slow wave ws observed soon after recirculation. The higher the administered dosage is, the better the degree of recovery of EEG was seen. Thus, the dose-related recovery of EEG was observed within the dose ranges tested.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Protective effect of phenytoin and its enhanced action by combined administration of mannitol and vitamin E in cerebral ischemia]. 308 96

To study the therapeutic effect of phenytoin on cerebral ischaemia and confirm whether or not the effectiveness of phenytoin could be enhanced by combined administration with free radical scavengers, twenty-five dogs were subjected to ischaemia, using the "canine model of the completely ischaemic brain regulated with a perfusion method". Five animals served as untreated controls, fifteen received treatment with several doses of phenytoin and five were treated with 10 mg/kg phenytoin, 2 g/kg mannitol and 30 mg/kg vitamin E. These drugs were administered prior to the production of ischaemia. After one hour ischaemia, cerebral blood flow was restored and the recovery of electrical activity of the brain and the degree of brain swelling were observed for three hours. With regard to the recovery of the EEG, the higher the administered dosage, the better was the degree of recovery of the EEG. And the group which was treated with a combination of phenytoin, mannitol and vitamin E exhibited remarkable recovery of the EEG. With regard to the degree of brain swelling, a similar dose-related suppressive effect was seen in the phenytoin-treated groups. Furthermore, in the combination therapy group, brain swelling was attenuated significantly. Based on these results, it is concluded that phenytoin has a protective effect in cerebral ischaemia and it shows its most remarkable effect when given together with radical scavengers, such as mannitol and vitamin E.
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PMID:Protective effect of phenytoin and its enhanced action by combined administration with mannitol and vitamin E in cerebral ischaemia. 312 29

We have previously demonstrated that the preischemic administration of perfluorochemicals (PFC) in combination with 20% mannitol, vitamin E and dexamethasone is effective in protecting the brain from cerebral ischemia. This experimental study was designed to evaluate the effect and limitation of the post-ischemic administration of those 4 agents on cerebral ischemia. We used "Canine model of complete ischemic brain regulated with a perfusion method." Using this model we were able to control the amount of blood flow to the left cerebral hemisphere by using an infusion pump. Infusion blood volume was reduced to 30%, 40% or 50% of the normal state, then the combined treatment was started 1,2,3,4,5 or 6 hours after the onset of ischemia in each ischemic group. By monitoring the EEG for 8 hours of ischemic period, we were able to evaluate the effect of the drugs on cerebral ischemia. In untreated groups, electrical activity deteriorated gradually. In the 30% ischemia group, the EEG became isoelectric within 1 hour following ischemia. In half of the 40% ischemia group, the EEG became isoelectric but in the other half low voltage slow wave were seen to last for 6-8 hours. In the 50% group, the EEG deteriorated gradually but did not disappear within 8 hours. The effectiveness of the treatment was judged by the degree of the recovery of electrical activity. The effectiveness of the treatment appeared to depend on the severity and the duration of ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Effects of cerebral protective agents in experimental cerebral ischemia. Relationship between the degree of ischemia and EEG]. 393 42

We have previously reported that the combined administration of mannitol and perfluorochemical blood substitutes is evidently effective in protecting the brain from cerebral ischemia. This experimental study was designed to develop more effective method in suppressing brain infarction than the combined treatment of mannitol and PFC. Using the "Canine model of complete ischemic brain regulated with a perfusion method" in which it is possible to control the degree of blood flow to a cerebral hemisphere via a perfusion pump, the effect of eight agents including six kinds as the free radical scavenger on cerebral ischemia was investigated. Eight agents were mannitol, vitamin E (Vit. E), dimethyl sulfoxide (DMSO), vitamin C, glycerol, nizofenone (Y-9179), dexamethasone (Dexa.) and suloctidil (MY-103). After pretreatment with each agent, blood flow was reduced via the pump to 1/10 of the normal state and 1 hour later, return to the normal state was allowed. Subsequent changes in EEG were observed and the effects of the drugs evaluated. In the control group, no recovery of electrical activity was seen, but in six groups among eight treated groups, i.e., treated with mannitol, Vit. E, DMSO, MY-103, Y-9179 and Dexa, gradual emergence of slow waves was observed. And more favorable effects were found when the combined administration of mannitol, Vit. E and Dexa was made in the same experimental schedule as compared with the single administration of each of these drugs. Furthermore in the animals administered with PFC in combination with mannitol, Vit. E and Dexa, flattening of electrical activity could not be seen throughout the period of severe ischemia. Moreover, the power of electrical activity recovered nearly to the preischemic state immediately after recirculation. Although the possible mechanisms are not yet completely clarified, the present results are thought to indicate that this new combination therapy utilizing PFC with mannitol, Vit. E and Dexa may be useful in the treatment of cerebral ischemia.
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PMID:[Experimental study of cerebral protective effect on cerebral ischemia of various antioxidants and other agents. With special reference to the combined treatment of mannitol, vitamin E, dexamethasone and perfluorochemicals]. 632 77


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