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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 cerebral ischemia on the activity of pyruvate dehydrogenase (PDH) enzyme complex (PDHC) was investigated in homogenates of frozen rat cerebral cortex following 15 min of bilateral common carotid occlusion ischemia and following 15 min, 60 min, and 6 h of recirculation after 15 min of ischemia. In frozen cortical tissue from the same animals, the levels of labile phosphate compounds, glucose, glycogen, lactate, and pyruvate was determined. In cortex from control animals, the rate of [1(-14)C]pyruvate decarboxylation was 9.6 +/- 0.5 nmol CO2/(min-mg protein) or 40% of the total PDHC activity. This fraction increased to 89% at the end of 15 min of ischemia. At 15 min of recirculation following 15 min of ischemia, the PDHC activity decreased to 50% of control levels and was depressed for up to 6 h post ischemia. This decrease in activity was not due to a decrease in total PDHC activity. Apart from a reduction in ATP levels, the acute changes in the levels of energy metabolites were essentially normalized at 6 h of recovery. Dichloroacetate (DCA), an inhibitor of PDH kinase, given to rats at 250 mg/kg i.p. four times over 2 h, significantly decreased blood glucose levels from 7.4 +/- 0.6 to 5.1 +/- 0.3 mmol/L and fully activated PDHC. In animals in which the plasma glucose level was maintained at control levels of 8.3 +/- 0.5 mumol/g by intravenous infusion of glucose, the active portion of PDHC increased to 95 +/- 4%. In contrast, the depressed PDHC activity at 15 min following ischemia was not affected by the DCA treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pyruvate dehydrogenase activity in the rat cerebral cortex following cerebral ischemia. 271 7

The objective of this study was to determine whether administration of dichloroacetate (DCA), an activator of pyruvate dehydrogenase (PDH), improves recovery of energy metabolites following transient cerebral ischemia. Gerbils were pretreated with DCA, and cerebral ischemia was produced using bilateral carotid artery occlusion for 20 min, followed by reperfusion up to 4 h. DCA had no effect on the accumulation of lactic acid and the decrease in ATP and phosphocreatine (PCr) during the 20-min insult, nor on the recovery of these metabolites measured at 20 and 60 min reperfusion. However, at 4 h reperfusion, levels of ATP and PCr were significantly higher in DCA-treated animals than in controls, as PCr exhibited a secondary decrease in caudate nucleus of control animals. PDH was markedly inhibited at 20 min reperfusion in both groups, but was reactivated to a greater extent in DCA-treated animals at 60 min and 4 h reperfusion. These results demonstrate that DCA had no effect on the initial recovery of metabolites following transient ischemia. However, later in reperfusion, DCA enhanced the postischemic reactivation of PDH and prevented the secondary failure of energy metabolism in caudate nucleus. Thus, inhibition of PDH may limit the recovery of energy metabolism following cerebral ischemia.
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PMID:Effect of dichloroacetate on regional energy metabolites and pyruvate dehydrogenase activity during ischemia and reperfusion in gerbil brain. 272 37

The activity of electroencephalogram (EEG) and cortical somatosensory evoked potential (SEP) was suppressed during cerebral ischemia in rats subjected to the 4-vessel occlusion. Considerable variations were demonstrated in the decrease of phosphocreatine and ATP concentration during ischemia among the rats measured with 31P-NMR, accompanied with cerebral acidification. Hypercapnia, induced in the rats studied by the inhalation of a gas mixture of 30-40% CO2, suppressed the activity of EEG and cortical SEP. The cerebral acidification observed during the ischemia was more severe than that under the hypercapnia, implying that cerebral acidification is one of the possible causes for the decrease in the electrical activity of the brain during ischemia.
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PMID:Effect of cerebral ischemia and hypercapnia on cerebral pH studied with 31P-NMR and electrical activity in rat brain. 272 63

Effects of S-adenosyl-L-methionine (SAM) on the metabolism in ischemic brain were investigated. The ischemic model employed was an incomplete cerebral ischemia of the spontaneously hypertensive rat (SHR) produced by the occlusion of both common carotid arteries. One hundred mg/kg of SAM was administered (i.p.) 6 times from the beginning of occlusion at 30 min intervals. At 3 hr after the onset of occlusion, animals were killed by microwave irradiation and creatine phosphate (CrP), ATP, glucose, lactate and gamma-aminobutyric acid (GABA) contents in the brain were measured. SAM significantly mitigated both the reductions in CrP, ATP and glucose levels and the increase in GABA level due to the cerebral ischemia. In another set of experiments with the same experimental schedule, water content in the brain was examined. SAM significantly suppressed the increase in water content due to the cerebral ischemia. These results indicate ameliorating effects of SAM on the metabolism in ischemic brain.
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PMID:S-adenosyl-L-methionine ameliorates ischemic brain metabolism in spontaneously hypertensive rats. 273 57

Improvement of energy metabolism in ischemic cerebral tissue benefits the therapy of occlusive cerebrovascular disorders. In the present study, the effects of 6-(10-hydroxydecyl)-2,3-dimethoxy-5-methyl-1,4-benzoquinone (idebenone) on neurological signs, such as ischemic seizures, lactate and ATP contents of the cerebral cortex, and local cerebral blood flow, were assessed in stroke-prone spontaneously hypertensive rats (SHRSP) with experimentally induced cerebral ischemia. Experimental cerebral ischemia was caused by bilateral carotid artery occlusion (BCAO) in male SHRSP (8-10 weeks old). Pretreatment with idebenone (10-100 mg/kg, p.o.) for 3 or 10 days delayed the onset of ischemic seizure (acute stroke) and prolonged survival time in SHRSP roughly in a dose-dependent manner. When the compound (100 mg/kg, i.p.) was given once 30 min after BCAO, it exerted similar ameliorating effects on the neurological deficits. When idebenone (100 mg/kg for 3 days) was given orally, it did not significantly inhibit the decrease in regional cerebral blood flow induced by BCAO. However, the same treatment markedly inhibited increases in the lactate content and lactate/pyruvate ratio and the decrease in ATP content of the cerebral cortex. The compound did not affect cerebral blood flow in normal rats. These results suggest that idebenone ameliorates the neurological deficits related to cerebral ischemia, and that this effect is mediated by improving cerebral energy metabolism.
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PMID:Effects of idebenone on neurological deficits, local cerebral blood flow, and energy metabolism in rats with experimental cerebral ischemia. 276 37

Cerebral ischemia was induced by a 200-s occlusion of both common carotid arteries in rats in which both vertebral arteries had been permanently cauterized. In the ischemic rats, a significant decrease in acetylcholine (ACh) and a marked increase in choline were observed in the cerebral cortex, hippocampus, striatum, and diencephalon. A slight increase in choline was also observed in the cerebellum and brain stem. Pretreatment with idebenone (10 mg/kg, i.p.) inhibited the decrease in ACh and the increase in choline in the forebrain regions. In addition, the same dose of idebenone inhibited the increments of lactate and free fatty acid contents and tended to inhibit the decrement of the ATP content in the cerebral cortex of the cerebral ischemic rats. These results indicate that idebenone inhibits the alteration of the ACh level and the disruption of membrane phospholipids in the brain of ischemic rats; these effects may be mediated by improved cerebral energy metabolism.
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PMID:Effects of idebenone on the levels of acetylcholine, choline, free fatty acids, and energy metabolites in the brains of rats with cerebral ischemia. 276 42

The present study was designed to examine the effect of chronic type 2 (noninsulin-dependent) diabetes mellitus on cerebral blood flow and metabolism during cerebral ischemia induced by bilateral carotid artery occlusion in spontaneously hypertensive rats. Diabetes was produced by streptozotocin treatment in 2-day neonates and the experiment was performed at the age of 5 months. The level of mean arterial pressure was not different between diabetic and nondiabetic rats. At 1 h after ischemia, cerebral blood flow was decreased to 1% of the resting value and supratentorial lactate was increased by 8-fold of control, being virtually the same in both groups of rats. In contrast, reduction of cerebral ATP was much less in diabetic rats (1.64 +/- 0.15 mmol/kg) than in nondiabetic rats (0.74 +/- 0.07 mmol/kg) (p less than 0.001); ATP in nonischemic control is 2.80-2.85 mmol/kg. These results could not be explained by the difference in cerebral blood flow between the groups during ischemia. The results suggest that chronic mild hyperglycemia exerts rather a protective effect on the brain against ischemic insult. Effective utilization of metabolites, such as glucose and ketone bodies, may play an important role to minimize metabolic derangements in the ischemic brain in type 2 diabetic-hyperglycemic rats.
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PMID:Cerebral ischemia in spontaneously hypertensive rats with type 2 (noninsulin-dependent) diabetes mellitus, cerebral blood flow and tissue metabolism. 279 88

The existence of uric acid in mammalian brain was recently reported, but it has not yet become a consensus. The mammalian brain has been thought to lack xanthine oxidase, which catalyzes hypoxanthine to xanthine and xanthine to uric acid as the last steps of ATP degradation in other tissue. Using high-performance liquid chromatography, we performed assays for hypoxanthine, xanthine, and uric acid in rat brain after cerebral ischemia. It was confirmed that all three substances showed significant augmentation in the removed brains and that the chronological order of those increases corresponded to the order in the metabolic pathway. Allopurinol, a specific inhibitor of xanthine oxidase, significantly suppressed the increases in uric acid and xanthine, and a compensatory accumulation of hypoxanthine was observed. From these results, it was concluded that uric acid does exist in the brain, increases after ischemia, and is possibly the end product of purine degradation in the brain. Furthermore, it is suggested that xanthine oxidase exists in the brain and catalyzes the reaction from hypoxanthine to xanthine and then to uric acid. These reactions catalyzed by xanthine oxidase are considered to be a source of free radicals and may play important roles in the pathogenesis of cerebral ischemic injury.
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PMID:Cerebral uric acid, xanthine, and hypoxanthine after ischemia: the effect of allopurinol. 279 98

Two simple cerebral ischemic models of mice were used for studying brain energy metabolism and the effects of drugs. Model one is partial occlusion of the left carotid artery and total occlusion of the right one including the vagus. The behavior of the animals appeared splaying of the contralateral extremities, circling around counterclockwise and in a comatose motionless state. Following the designated ischemic time, the animals were put into liquid N2. Model two is decapitation induced ischemia of mouse brain. The whole animal (control) and the severed head were rapidly frozen in liquid nitrogen 0, 10, 30, 60 s after decapitation. Brain samples were powdered at liquid N2 temperature, extracted and determined for ATP, phosphocreatine (Pcr) and lactic acid (LA). The data from model one indicate that after an ischemic period of 10 min, brain LA level increased significantly compared with values from the sham operated group, while no significant alteration was observed in brain ATP, and Pcr level. At 180 min of ischemia, levels of ATP and Pcr were considerably reduced while LA level increased significantly. The degree of symptoms induced by brain ischemia showed good correlation with brain energy metabolism. In model 2 brain LA level was found to be increased, while ATP and Pcr levels decreased after whole brain ischemia. However, brain ATP and Pcr levels were increased and LA level was decreased significantly in the normal and ischemic animal after administration of phenobarbital (225 mg/kg ip). LA level decreased significantly in the unischemic mice treated with Rb1 (100 mg/kg ip). It is indicated that both models of cerebral ischemia were simple and sensitive methods for studying brain ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Brain energy metabolism of cerebral ischemic mice and the effects of some drugs]. 280 Nov 43

Swelling of astrocytes in the brain is a major cause of the morbidity and mortality associated with stroke and head trauma. Using a human astrocytoma cell line (UC-11MG) as a model system, we studied cell volume changes caused by ATP depletion under conditions mimicking hypoxia. ATP levels were reduced to less than 10% of control using the metabolic inhibitors KCN or antimycin in combination with glucose deprivation. This was sufficient to eliminate ouabain-sensitive 86Rb+ uptake, indicating the Na+-K+-adenosinetriphosphatase was not operating. Furosemide-sensitive 86Rb+ uptake was reduced by approximately 60%, indicating Na+-K+-2Cl- cotransport was also sensitive to ATP loss. ATP depletion resulted in a 30-40% reduction of cell volume within 60 min. ATP depletion also resulted in a net loss of intracellular K+. This loss of K+ could be blocked by Ba2+, indicating the K+ loss was through a conductive channel. When the net K+ loss was blocked by Ba2+, the volume decrease was also prevented. The cells remained viable throughout the time period as judged by exclusion of ethidium bromide by 99% of the cells and recovery of ATP levels to 75% of control within 60 min. We conclude that ATP depletion, following inhibition of glycolysis and oxidative phosphorylation, causes astrocytes to shrink because of a more rapid loss of K+ than uptake of Na+. Thus it appears that ATP depletion alone is not sufficient to account for the rapid phase of astrocytic swelling observed during cerebral ischemia.
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PMID:Energy-dependent cell volume maintenance in UC-11MG human astrocytomas. 280 31


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