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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We assessed the effect of 1,3-butanediol on cerebral energy metabolism and edema after inducing multifocal brain infarcts in 108 rats by the intracarotid injection of 50-microns carbonized microspheres. An ethanol dimer that induces systemic ketosis, 25 mmol/kg i.p. butanediol was injected every 3 hours to produce a sustained increase in the plasma level of beta-hydroxybutyrate. Treatment significantly attenuated ischemia-induced metabolic changes by increasing the concentrations of phosphocreatine, adenosine triphosphate, and glycogen and by reducing the concentrations of pyruvate and lactate. Lactate concentration 2, 6, and 12 hours after embolization decreased by 13%, 44%, and 46%, respectively. Brain water content increased from 78.63% in six unembolized rats to 80.93% in 12 saline-treated and 79.57% in seven butanediol-treated rats 12 hours after embolization. (p less than 0.05). The decrease in water content was associated with significant decreases in the concentrations of sodium and chloride. The antiedema effect of butanediol could not be explained by an osmotic mechanism since equimolar doses of urea or ethanol were ineffective. Our results support the hypothesis that the beneficial effect of butanediol is mediated through cerebral utilization of ketone bodies arising from butanediol metabolism, reducing the rate of glycolysis and the deleterious accumulation of lactic acid during ischemia.
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PMID:Beneficial effect of 1,3-butanediol on cerebral energy metabolism and edema following brain embolization in rats. 221 11

Functional assessment of animals following experimental cerebral ischemia is often difficult due to the passive nature of many neurologic exams. We attempted to increase the objectivity of motor function evaluation by adapting quantifiable behavioral tests and actively testing rats' motor capability following a cerebral ischemic insult. It was hypothesized that active testing would reveal motor deficits which were not readily apparent upon casual observation and that such testing would provide a more sensitive means of experimental neurologic assessment. Wistar rats were exposed to reversible severe forebrain ischemia using the four-vessel occlusion technique. Motor function was evaluated using the total motor score (sum of scores for screen test, balance beam test, and prehensile-traction test) over the 48 hours which followed 20 minutes of cerebral ischemia. To manipulate neurologic outcome, rats were fed or fasted the day prior to ischemia and then pretreated with either 1,3-butanediol or saline. Fasted saline-treated animals demonstrated improved total motor performance compared with fed animals by 48 hours after ischemia. There was no improvement in motor performance by fasted vs. fed rats from among the butanediol-treated animals. Pretreatment with butanediol resulted in significantly better total motor performance among fasted rats 24 hours after ischemia; however, by 48 hours postischemia, no difference was detectable. This is the first demonstration of motor deficits produced by four-vessel occlusion in rats. The motor tests devised appear to be adequately sensitive to detect changes in motor function that are not apparent with passive observation in this model.
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PMID:Motor performance in rats exposed to severe forebrain ischemia: effect of fasting and 1,3-butanediol. 356 10

1,3-Butanediol (BD) is converted in the body to beta-hydroxybutyrate, and previous studies have shown that hyperketonemia had beneficial effects in experimental models of generalized hypoxia. The aim of this study was to determine if BD would reduce brain damage following cerebral ischemia. A transient forebrain ischemia of 30-min duration was induced by the four-vessel occlusion technique in control and BD-treated rats (25 mmol/kg, i.p.; 30 min prior to ischemia). BD treatment led to significant improvement of neurologic deficit during the 72-h recovery period and reduced neuronal damage in the striatum and cortex but not in the CA1 sector of the hippocampus. Evaluation of cerebral energy metabolism before and at the end of the ischemic period showed that the treatment did not change the preischemic glycolytic and energy metabolite levels but attenuated the ischemia-induced metabolic alterations. It increased energy charge, phosphocreatine, and glucose levels, and reduced lactate accumulation. The decrease in brain lactate concentration might account for the beneficial effects of BD by minimizing the neuropathological consequences of lactic acidosis.
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PMID:Protective action of 1,3-butanediol in cerebral ischemia. A neurologic, histologic, and metabolic study. 369 36

This study examined the effect of 1,3-butanediol on the selective loss of CA1 pyramidal neurons following a short period of near-complete forebrain ischemia. Injection of 55 mmol 1,3-butanediol/kg body weight at 24 h of recirculation and again at 36 h following 10 min of forebrain ischemia markedly reduced damage to CA1 neurons examined at 72 h of recirculation compared with that in saline-treated rats. Comparable treatment with ethanol did not cause significant protection. Neuronal loss was also not reduced by 1,3-butanediol treatment when the ischemic period was extended to 15 min or by single treatments at 24 h or 36 h following 10 min of ischemia. However, a single treatment 5 min after reversal of 10 min of ischemia was effective in ameliorating cell loss. The difference in effectiveness of 1,3-butanediol following 10 min and 15 min of ischemia is consistent with a number of previous studies, indicating that the processes leading to loss of CA1 neurons are modified when the ischemic period is extended. Previous findings that 1,3-butanediol reduced damage in other ischemia-susceptible neuronal subpopulations but not in CA1 neurons most likely reflected the longer period of ischemia which was used. The results of the present investigation demonstrate that administration of 1,3-butanediol offers a novel approach for interfering with post-ischemic loss of CA1 neurons following a brief ischemic period which is effective even when initiated after prolonged recirculation periods.
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PMID:Delayed treatment with 1,3-butanediol reduces loss of CA1 neurons in the hippocampus of rats following brief forebrain ischemia. 785 74

Previous studies have shown that 1,3-butanediol (BD) has beneficial effects in experimental models of hypoxia or ischemia but the mechanism by which it exerts its protective effects remains unknown. BD is converted in the body to beta-hydroxybutyrate (BHB) and it has been proposed that its effects were linked to its ketogenic effect. The effects of BD (25 and 50 mmol/kg) on cerebral energy metabolism of rats were studied by measuring the cerebral level of energy metabolites and by evaluating the cerebral metabolic rate according to the Lowry's method. BD induced an increase in [cortical glucose]/[plasma glucose] ratio which was associated with a decrease in lactate level and an increase in glucose and glycogen stores. In contrast, BHB treatment which mimicked hyperketonemia equivalent to BD did not modify cerebral glycolysis metabolites. Calculation of the energy reserve flux after decapitation showed that BD did not reduce the cerebral metabolic rate excluding a protective effect due to a depressant, barbiturate-like, action. These results suggest that BD induces a reduction of cerebral glycolytic rate. However, the effect is not linked to hyperketonemia but might be due to intracerebral conversion of BD to BHB.
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PMID:Effect of 1,3-butanediol on cerebral energy metabolism. Comparison with beta-hydroxybutyrate. 807 65

1,3-Butanediol (BD) treatment was previously shown to produce a dose-related increase of the plasma levels of D-beta-hydroxybutyrate (BHB) and to protect brain tissue against hypoxia and ischemia. The purpose of this study was to test whether BD-induced hyperketonemia was associated with changes in brain extracellular and tissue concentrations of BHB. Changes in extracellular levels of BHB were continuously monitored in anesthetized rats before and after intraperitoneal injection of BD (25 mmol/kg), using intracerebral microdialysis coupled to online analysis of BHB in the dialysate. Cortical tissue concentrations of BHB were determined in control and BD-treated rats (25 and 50 mmol/kg, i.p.) after freezing of the brain in situ. Butanediol produced a rapid increase in dialysate levels of BHB, with a linear relationship between dialysate and plasma BHB concentrations (r = 0.81, p < 0.001). In contrast, and although brain tissue levels of BHB were markedly increased after BD treatment, they were not related to the plasma concentration of BHB. Our results suggest that BHB produced from BD did not accumulate in brain and that BD protects against hypoxia or ischemia by increasing brain BHB availability.
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PMID:Changes in extracellular and rat brain tissue concentrations of D-beta-hydroxybutyrate after 1,3-butanediol treatment. 826 21

The aim of the present work was to evaluate the protective properties of the calcium-entry blocker nimodipine against brain damage induced by cardiopulmonary arrest in a rat model. We studied first the effect of nimodipine administered in a blind and randomized fashion and started 5 min after the restoration of spontaneous circulation. Our experiments showed no improvement of survival, and nimodipine did not improve the neurological outcome in the animals surviving after 7 days. We even observed a trend toward a decreased survival rate when higher doses of nimodipine were used. In order to evaluate whether the lack of protective effect of nimodipine might have been due to the fact that it was given too late, we administered nimodipine in the second series of experiments at the earliest feasible postischemic moment, i.e. at the start of the resuscitation attempts. However, this study also failed to show an improved outcome in nimodipine-treated animals; there was even a significantly decreased resuscitation rate. In order to exclude that a cerebroprotective effect was antagonized by deleterious effects of nimodipine on the cardiovascular system, which may be especially vulnerable after resuscitation, we also studied nimodipine in the 4-vessel occlusion model in the rat. Indeed, in contrast to the cardiopulmonary arrest model, cardiovascular depression does not occur in this model. In these experiments, we started the administration of nimodipine before the induction of global brain ischemia, used 2 different dosage regimens and provided prolonged drug administration after restoration of cerebral blood flow in order to create optimal circumstances for a cerebroprotective effect to be detected. These experiments, however, also failed to show any cerebroprotective effect of nimodipine. In this 4-vessel occlusion model, we also evaluated, as a control drug, 1,3-butanediol, an alternate substrate for brain metabolism during ischemia that has been shown to offer cerebral protection in this animal model. Our results could, however, not confirm this beneficial effect. We conclude that in the rat there is no cerebroprotective effect of the calcium-entry blocker nimodipine on global brain ischemia as present during cardiopulmonary arrest. On the contrary, we even observed adverse effects, especially when high doses are used and/or when the drug is given during resuscitation attempts.
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PMID:Pharmacological influences on cardiopulmonary arrest-related brain damage in the rat. 848 Apr 49

DL-1,3-butanediol (DL-BD) is an ethanol dimer which affords cerebral protection in various experimental models of hypoxia and ischemia but its mechanism of action is unknown. DL-BD is a ketogenic alcohol and it has been proposed that its protective effect was accomplished through cerebral utilization of ketone bodies. Since DL-BD is a racemic, its metabolic effects could be due to D, L or both isomers. The effects of equimolar doses of DL-, D- and L-BD (25 mmol/Kg) on cerebral metabolism were studied by measuring the cortical levels of the main glycolytic (glycogen, glucose, glucose 6-phosphate, fructose 1,6-diphosphate, pyruvate and lactate) and citric acid cycle (citrate, alpha-ketoglutarate and L-malate) intermediates. The two BD isomers exerted different effects on cerebral metabolism. Unlike L-BD, D- and DL-BD treatments resulted in a slight (+10%) but significant increase in citrate level whereas L-BD treatment led to significant reduction in pyruvate (-12%) and lactate (-24%) levels. These effects were apparently not linked to hyperketonemia, since DL-BHB treatment, which mimicked hyperketonemia induced by DL-BD, had no effect on cerebral metabolites but might be due to intracerebral metabolism of BD.
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PMID:Effect of D- and L-1,3-butanediol isomers on glycolytic and citric acid cycle intermediates in the rat brain. 884 93