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

The peculiarities of brain energy metabolism were studied in male rats before and during cerebral ischemia of various severity elicited by bilateral common carotid arteries ligation. A multidimensional analysis was applied. In the rats which died after the ischemia, the NAD + NADH+/phosphocreatine (PCr) ratio and ATP content before ligation were higher than those in the surviving group. Also the strength of relationships between parameters of NMR spectra in each correlation matrix were 10 times higher and the variability of elements in each matrix was significantly lower in victims than those in the surviving group. The development of severe ischemia and the animals death were accompanied by an increase in the inorganic phosphate content, decrease in pH and stepwise disappearing of PCr and ATP. In animals surviving the same brain ischemia model, the changes in 31P spectra parameters pointed to some increase in the ratio of NAD + NADH+ only to ATP + ADP but not to PCr, and to an increase in summarized strength of correlation between 31P spectra parameters with the variability of elements decreased within each correlation matrix. Detection of these changes can be helpful in the diagnosis of mild ischemia without neurological deficit which already needs preventive therapy against more severe ischemia.
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PMID:[Changes in energy metabolism in the brain in experimental cerebral ischemia of different degree of severity (nuclear magnetic resonance-spectroscopic study)]. 260 23

We describe a series of experiments in which a subhuman primate model was used to create temporary and permanent cerebral ischemia by three separate mechanisms. In the first group of five baboons, a hemodynamic model was produced by creating unilateral and bilateral carotid stenotic lesions of varying degrees with and without associated reduction in systemic perfusion pressure. Only global ischemic changes and no focal changes resulted. In the second group of three baboons, a macroembolic model was produced by introducing solid particulate material into the extracranial circulation. No reversible contralateral focal neurologic changes resulted. In the third group of 11 baboons, cerebral ischemia was produced by introducing agents known to cause platelet aggregation (arachidonic acid, adenosine diphosphate, and collagen) into the extracranial arterial circulation. Arachidonic acid caused seizures, adenosine diphosphate caused severe postural hypotension, and only collagen fibrils produced a picture resembling a transient ischemic attack. We propose a theory that intravascular activation of the prostaglandin cascade by chemical initiation may result in the pathophysiologic changes of transient cerebral ischemia.
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PMID:Pathogenesis of transient ischemic attacks and stroke in baboons. 292 78

The present investigation was designed to examine the effects of free arachidonic acid (20:4), in concentrations relevant to cerebral ischemia, on brain mitochondrial respiratory activities and the reversibility of these effects. Incubation of brain mitochondria with 20:4 caused a dose-dependent increase in substrate-supported (state 4) respiration (i.e., uncoupling) and a concomitant inhibition of substrate-, phosphate-, and ADP-supported (state 3) or dinitrophenol-supported state (3u) respiration. The temperature dependence of the 20:4 effects on mitochondrial respiration was also studied. It was found that the uncoupling and the respiratory inhibition were at least as pronounced at physiological temperatures as at room temperature. Arrhenius plots of the state 3 respiratory rates suggested that 20:4 did not cause a significant change in membrane fluidity. Addition of bovine serum albumin to the reaction medium following preincubation with 20:4 reversed the uncoupling effect but only partly reversed the inhibition of state 3 respiration. The results suggest 1) that 20:4 may inhibit mitochondrial ATP production during conditions of incomplete cerebral ischemia and 2) that 20:4 may limit the postischemic recovery of mitochondrial function.
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PMID:Effects of arachidonic acid on respiratory activities in isolated brain mitochondria. 312 46

Mitochondrial function was examined in cats after 1 h of complete cerebral ischemia and subsequent recirculation periods from 15 min to 56 h. During ischemia the NAD-linked respiratory control ratio and the maximal phosphorylation capacity of "free" and synaptosomal mitochondria decreased to 53% to 76% of control values. During postischemic reperfusion to 6 h, mitochondrial function was restored to 80%, remaining less than control throughout the entire investigated recirculation period with a tendency of secondary deterioration from 12 h of reperfusion onward. ADP: O ratios were unaffected during ischemia, but decreased significantly during early recirculation (15 to 30 min), and were completely restored from 45 min reperfusion onward. Correlation with electrophysiologic recordings revealed that mitochondrial dysfunction was not a limiting factor for neurophysiologic recovery during early recirculation (15 to 90 min). When the recirculation period was extended (greater than 3 h), good neurophysiologic recovery was associated with a return of mitochondrial function to control levels; inversely, poor mitochondrial function was correlated with poor neurophysiologic recovery.
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PMID:Mitochondrial respiration during recirculation after prolonged ischemia in cat brain. 356 58

Nimodipine is known to improve postischemic cerebral blood flow (CBF) and neurologic outcome in experimental animals. Whether or not the two observations are related is unknown. This study searched for a possible improved rate of brain metabolic recovery in animals treated with nimodipine postischemia. Complete cerebral ischemia was produced for 11 min in 16 dogs, followed by reperfusion for 70 min. Prior to ischemia, glucose was administered (0.75 g X kg-1) in 12 dogs. Half of the glucose-treated dogs were given i.v. nimodipine, beginning 5 min postischemia (10 micrograms X kg-1 bolus followed by 1 microgram X kg-1 X min-1). The other half were given only saline postischemia. The remaining four dogs were given no glucose and received saline only postischemia. In all dogs, serial brain biopsies were taken at 2, 20, 40, and 70 min postischemia. In 5 dogs, the integrity of the blood-brain barrier (BBB) was tested by injection of Evans blue dye and postmortem examination of the brains. Brain biopsies were assayed for concentrations of phosphocreatine, ATP, ADP, AMP, glucose, lactate, and pyruvate. In all dogs, there was rapid restoration of a normal brain energy state following reperfusion. Brain lactate had returned to near normal in all dogs by 70 min postischemia, and the rate of lactate depletion was not different between groups. The integrity of the BBB was only minimally affected. A portion of the brain lactate was converted to pyruvate rather than crossing the BBB.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Nimodipine does not affect cerebral lactate levels following complete ischemia in dogs. 365 2

The in vitro thiobarbituric acid test was used as a measure of lipid peroxidation in the gerbil and rat. Synaptosomal preparations were isolated from the cerebral cortex of each species and incubated with a free radical generating system. Varying concentrations of ADP-Fe3+, with ascorbate and oxygenated incubation medium were used to generate hydroxy-radicals. Peroxidation of the synaptosomal membrane lipids was determined using malondialdehyde (MDA) accumulation. Both the gerbil and rat demonstrated significant increases in MDA in the presence of the generating system, while the gerbil P2 fraction consistently showed an increased level of MDA accumulation as compared with rat at each of the concentrations of ADP-Fe3+. Across a range of concentrations, there was a 2-2.6-fold greater increase in MDA accumulation in gerbil as compared with rat. Free radical generation is currently thought to be involved in the associated damage following cerebral ischemia. An in vitro model capable of producing biochemically similar damage to membrane systems by means of a controlled free-radical generating system may prove useful in studying possible mechanisms of ischemic damage.
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PMID:Increased in vitro lipid peroxidation of gerbil cerebral cortex as compared with rat. 372 2

We tested the antiplatelet effects of low-dose aspirin in patients with occlusive cerebrovascular disease, because conventional dosage aspirin inhibits vascular synthesis of prostacyclin at the same time that it inhibits platelets. The effects on platelet function and thromboxane A2 synthesis of 40 mg of aspirin daily or 40 mg aspirin plus dipyridamole were measured in 23 patients starting within a week after the onset of cerebral ischemia. All patients had normal baseline platelet aggregation responses to four stimuli: arachidonate, epinephrine, adenosine diphosphate and collagen. The generation of thromboxane A2 by platelets, measured as serum thromboxane B2, was also normal. After 3 to 7 days of low dose aspirin therapy, platelet aggregation responses were suppressed to the extent observed with higher dosage aspirin. Serotonin release during platelet aggregation was inhibited by more than 95% and thromboxane B2 levels in clotted blood fell by more than 95%. Responses to aspirin treatment were similar in patients with transient ischemic attacks and in those with stroke and were also similar in both sexes. No differences in platelet responses were observed between patients receiving aspirin alone and aspirin plus dipyridamole. Thus 40 mg aspirin daily inhibited platelet responses as effectively as higher doses of aspirin in patients who had recent cerebral ischemia and showed a cumulative antiplatelet effect.
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PMID:Effects of low dose aspirin on platelet function in patients with recent cerebral ischemia. 396 66

The intravascular adhesion and aggregation of platelets initiate hemostasis and arterial thrombosis. In vitro, platelet aggregation is induced by many different agents; which of these is responsible for aggregation in vivo is now under investigation. For this purpose, we have developed novel techniques for the reproducible determination of bleeding times in mesenteric arterioles of rats and rabbits. Local infusions of enzyme systems which remove adenosine diphosphate (ADP) greatly increase the bleeding time at arterial injuries distal to the site of infusion. These observations establish the involvement of ADP in the activation of platelets for primary hemostasis. Direct measurement of free adenosine triphosphate (ATP), as an indicator of ADP, at such injury sites indicates that enough ADP for activating platelets is released very rapidly from damaged vessel walls and much later from the platelets themselves. This bleeding-time technique has also shown that hemostatic platelet aggregation is delayed less by the inhibition of the production of thromboxane A2 than by that of ADP. These observations provide an explanation for the ineffectiveness of any simple platelet-inhibiting drug (including aspirin) by itself, whenever arterial (e.g., coronary or cerebral) thrombosis is initiated by hemorrhages into atheromatous plaques. On the other hand, aspirin is significantly effective when myocardial infarction follows unstable angina and when strokes follow transient episodes of cerebral ischemia. This partial effectiveness can be explained by an action of aspirin on platelets, assuming that, in such cases, their thromboembolic aggregation is initiated by hemodynamic effects of atheromatous lesions.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Platelets and blood vessels. 608 14

Phosphatic metabolite (perchloric acid extractable) concentrations of cerebral tissues were analyzed by phosphorus-31 nuclear magnetic resonance (P-31 NMR) spectroscopy following external perfusion of the isolated rat brain (30 min or 60 min) under the following conditions: (a) constant perfusion pressure with either fluorocarbon- or erythrocyte-based medium, and (b) constant perfusate flow rate (3 ml/min) with the erythrocyte-based medium. Metabolite concentrations of control perfused brains were compared with those in nonperfused controls to provide a basis for detecting any qualitative or quantitative changes in cerebral metabolite composition. Metabolic responses of perfused brains to ischemia (incomplete ischemia, 83% reduction in flow for 10 min; transient complete ischemia for 1.5 or 2 min) were evaluated immediately after the ischemic episode and at selected time points during reperfusion (3 and 15 min). Alterations in cerebral metabolite levels induced by hypoxia were analyzed using a nonperfused rat brain model. Irrespective of the perfusion method employed, the phosphatic metabolites of control perfused rat brains were identical quantitatively to those of the nonperfused controls. Cerebral ischemia resulted in significantly increased levels of ADP, AMP + IMP, Pi, fructose 1,6-diphosphate, and glycerol 3-phosphate (global ischemia only), whereas ATP and phosphocreatine (PCr) levels declined significantly. The magnitude of these changes varied with the severity of the ischemia; however, following 15 min of control reperfusion metabolite levels had reverted to preischemic values. Significant perturbations in tissue phosphoethanolamine (3.84 delta resonance) content were evident at various time points during ischemia and postischemic recovery, which varied according to the perfusion conditions. In contrast to the changes observed in response to ischemia, hypoxia affected only cerebral high-energy phosphate levels. ATP and PCr levels were reduced, while a concomitant, essentially equimolar, increase in Pi and ADP was observed. The present studies indicate that in terms of phosphatic metabolites, the control equilibrated isolated perfused rat brain is quantitatively and qualitatively indistinguishable from the nonperfused rat brain in vivo regardless of the perfusion conditions (constant flow versus constant pressure). The metabolic responses to ischemia and hypoxia, as measured by P-31 NMR, were consistent with the pattern of changes reported elsewhere. Overall, P-31 NMR spectroscopic evaluation of the intact rat brain provides a potential experimental context for dynamic measures of cerebral metabolism under exogenously controlled conditions. Th
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PMID:P-31 nuclear magnetic resonance analysis of brain: II. Effects of oxygen deprivation on isolated perfused and nonperfused rat brain. 609 45

We tested whether cerebral noradrenaline (NA) may play a central role in mediating the increased production of free fatty acids (FFAs) during cerebral ischemia. Levels of FFAs, cyclic AMP, and NA, as well as ATP, ADP, and AMP, were measured in cerebral cortex during decapitation ischemia in rats 2 weeks after unilateral locus ceruleus lesion. Comparisons were made between the results obtained from the contralateral cortex with normal NA content and the NA-depleted ipsilateral cortex. Although NA depletion was associated with a diminished transient rise of cyclic AMP in response to ischemia, it failed to influence the magnitude of FFA increase or the decline of energy state within the 15-min period of ischemia. A more than twofold increase of total FFAs (sum of palmitic, stearic, oleic, arachidonic, and docosahexaenoic acids) was observed in both hemispheres at 1 min after decapitation, when energy failure became manifest. The increased production of FFAs continued throughout the 15 min of ischemia, with a preferential rise in the levels of stearic and arachidonic acids. There was an inverse correlation between FFA levels and total adenylate pool. The results do not support a major role for NA and cyclic AMP in increasing cortical FFAs during complete ischemia. Instead, they are consistent with the view that impaired oxidative phosphorylation activates deacylating enzymes. Disturbance of reacylation due to energy depletion is probably another factor contributing to the continuous increase of FFAs during prolonged ischemia.
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PMID:Free fatty acids and energy metabolites in ischemic cerebral cortex with noradrenaline depletion. 631 5


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