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

The functional integrity of the N-methyl-D-aspartate receptor complex following focal cerebral ischemia in the rat has been examined at a time when brain tissue is irreversibly damaged. Twelve hours after unilateral permanent middle cerebral artery occlusion, [3H]-MK-801 binding was not significantly altered in the ischemic cerebral cortex compared to sham-operated animals. Moreover, the enhancement of [3H]MK-801 binding by exogenous glutamate was preserved in an area of the brain that was permanently damaged by the ischemic insult.
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PMID:Alterations in the N-methyl-D-aspartate receptor complex following focal cerebral ischemia. 257 Jul 87

Pathological conditions which interfere with normal brain energy metabolism causes similar neuronal degeneration. Cerebral ischemia, hypoglycemia, and status epilepticus are well known examples of such disease processes. Recently, it has come to be realized that the similarity of the pattern of neuronal degeneration is probably due to the toxicity of a putative neurotransmitter glutamate. Ischemic hippocampal damage in rodents has been studied as a typical experimental model. Following brief ischemia, the rodent hippocampus recovers completely and then starts degenerating over a few days. The delayed neuronal death of the hippocampus could be accounted for by excitotoxic action of glutamate. There is a considerable body of evidence to support this hypothesis. Extracellular glutamate actually increases following brief ischemia. Preceding destruction of glutamatergic input to the hippocampal CA1 (deafferentation) partially prevents ischemic neuronal damage in CA1. Various drugs are reportedly effective in preventing ischemic CA1 damage and some of them have a property of glutamate antagonist. However, why glutamate brings about cell necrosis is still not fully understood. Further study of basic mechanism is awaited.
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PMID:[Neuronal degeneration and glutamate]. 257 28

Glucose metabolism is altered in various pathologic conditions in the brain, i. e. ischemia, epilepsy and hypoglycemia. Therefore, analysis of glucose metabolism in pathologic conditions needs careful investigation of that in steady state. 13C-NMR method allows continuous sequential monitoring of changes in metabolism of glucose in vivo. The natural abundance of 13C is quite low (1.1%) and by administering 13C labelled in various skeleton in glucose, it is possible to monitor the metabolites in vivo. In this study, 13C glucose labelled in 1-position of carbon was employed to investigate the metabolic pathways in the control and transient ischemic gerbil brain with reperfusion. Male mongolian gerbils weighing 60-80 g were employed in this study. The gerbils were anesthetized by intraperitoneal administration of pentobarbital. The right skull was exposed and a surface coli was placed directly above the skull bone. After the operation, the animals were fastened to the NMR probe vertically. 500 mg/kg of [1-13C] glucose was injected via femoral catheter. 13C-NMR spectra were serially obtained before and after injection with GX-270 NMR spectrometer (JEOL, Tokyo, Japan, 6.34 T). In other series of experiments, 30 minutes of cerebral ischemia were induced after 15 minutes of glucose injection by the bilateral common carotid artery occlusion. In the normal gerbil brain, after administration of [1-13C] glucose (500 mg/kg), alpha and beta-anomers of [1-13C] glucose peak appeared abruptly and reached its peak level at 7.5-15 min acquisition period. The C2 peak representing glutamate and/or glutamine appeared later. The C3 and C4 peak started to appear even later at 30-40 min.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[The metabolism of glucose monitored by 13C-NMR in the gerbil brain in vivo-natural course and application to the ischemic model]. 273 47

The aim of this study was to measure changes in the extracellular fluid (ECF) concentration of lactate, pyruvate, purines, amino acids, dopamine, and dopamine metabolites in the striatum of rats subjected to focal cerebral ischemia, using intracerebral microdialysis as the sampling technique. Microdialysis probes were inserted into the lateral part of the caudate-putamen bilaterally 2 h before the experiment. Ischemia was induced by permanent middle cerebral artery occlusion (MCAO) on the left side. Microdialysis samples were analyzed by high performance liquid chromatography. Following MCAO, the concentration of lactate, adenosine, inosine, and hypoxanthine rose markedly in the ECF on the occluded side, while there was no significant change in pyruvate. These changes were accompanied by dramatically elevated levels of aspartate, glutamate, taurine, gamma-aminobutyric acid, and dopamine. There was also a marked increase in alanine/tyrosine, while minor or no changes occurred with other amino acids. Concomitantly, the ECF level of the dopamine metabolites 3,4-dihydroxyphenylacetate and homovanillic acid decreased. There was no significant increase in any of the metabolites measured on the right, nonoccluded side. In relation to the concept of excitotoxicity in brain ischemia, it is concluded that during the acute stage of focal cerebral ischemia, the ECF is flooded with both potentially harmful (e.g., aspartate, glutamate, and DA) and protective (e.g., taurine, GABA, and adenosine) agents. The relative importance of these events for the development of cell death in the ischemic penumbra needs to be elucidated. In addition, lactate, inosine, and hypoxanthine, measured in the ECF by intracerebral microdialysis, may prove to have diagnostic and/or prognostic value in neurometabolic monitoring of the ischemic brain.
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PMID:Dynamics of extracellular metabolites in the striatum after middle cerebral artery occlusion in the rat monitored by intracerebral microdialysis. 277 32

The effect of cerebral ischemia on extracellular amino acids and calcium content and on the permeability of the blood-brain barrier was studied by in vivo dialysis of rabbit hippocampus. This was combined with physiological and neurophysiological measurements. It was found that immediately after 15-min ischemia extracellular concentrations of glutamate, aspartate and taurine increased 3-, 2- and 6-fold, respectively, whereas a maximal, 7-fold increase of phosphoethanolamine and persistent elevation of glutamate were observed 45 min after ischemia. Extracellular calcium concentration, monitored with 45Ca2+, increased by 10% during the initial phase of ischemia, and decreased to approx. 74% of the basal level 10 min after ischemia. Recovery of extracellular calcium content was not attained until 45 min of recirculation, at which time the first signs of return of bioelectric activity were noted. Increased permeability of the blood-brain barrier to fluoresceine developed immediately after ischemia and persisted up to 2 h of recirculation. The obtained results are discussed in reference to the noted simultaneity of changes in extracellular excitatory amino acids and calcium concentrations and of brain bioelectric activity during and after ischemia. Causal relations between these effects are suggested.
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PMID:Early changes in extracellular amino acids and calcium concentrations in rabbit hippocampus following complete 15-min cerebral ischemia. 284 43

Recent studies have strongly implicated the excitatory neurotransmitter glutamate in the cascade of pathological mechanisms that cause neuronal loss after certain types of brain ischemia. The neurotoxic effects of glutamate are mediated, at least in global ischemia, via NMDA receptors. In the present study we have examined the effects of compounds that possess NMDA receptor antagonist properties (ifenprodil, SL 82.0715 [(+/-)-alpha-(4-chlorophenyl)-4-[(4-fluorophenyl)methyl]- 1-piperidineethanol] and 1-[1-(2-thienyl)cyclohexyl]piperidine) on the histological consequences of focal, as opposed to global, cerebral ischemia in both the rat and the cat. Ifenprodil (0.3-3 mg/kg i.v.) administered as a perfusion over 3 hr after occlusion of the feline middle cerebral artery reduced the volume of infarcted tissue (measured 4 days after occlusion) in a dose-related manner. At the highest dose a 42% reduction of infarcted volume was noted, essentially in cortical tissue. In an identical protocol, a derivative of ifenprodil, SL 82.0715, reduced the volume of infarction in a manner comparable to that described for ifenprodil. As SL 82.0715 possesses better p.o. bioavailability, this compound was also evaluated in the rat, again after middle cerebral artery occlusion. First administered 30 min after the induction of ischemia, SL 82.0715 (1 and 10 mg/kg p.o.) reduced infarction volume by 34 and 48%, respectively. The quantitative histology was performed 2 days after middle cerebral artery occlusion. The noncompetitive receptor antagonist, 1-[1-(2-thienyl)cyclohexyl]piperidine, administered (1 mg/kg i.p.) before the induction of focal ischemia, similarly and significantly decreased the final volume of infarction. As both ifenprodil and SL 82.0715 are noncompetitive antagonists of the NMDA receptor, two conclusions may be drawn from the present investigation. First, NMDA antagonism by ifenprodil and its derivative is an effective approach for tissue sparing in animal models of stroke and brain infarction. Second, these pharmacological observations provide evidence for the involvement of excitatory amino-acid induced-neurotoxicity in the evolution and consequences of focal cerebral ischemia.
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PMID:Ifenprodil and SL 82.0715 as cerebral anti-ischemic agents. I. Evidence for efficacy in models of focal cerebral ischemia. 284 68

The uptake and release of D-[3H]aspartate (used as a tracer for endogenous glutamate and aspartate) were studied in cultured glutamatergic neurons (cerebellar granule cells) and astrocytes at normal (5 mM) or high (55 mM) potassium and under conditions of hypoglycemia, anoxia or "ischemia" (combined hypoglycemia and anoxia). In glutamatergic neurons it was found that "ischemic" conditions led to a 2.4-fold increase in the potassium-induced release of D-[3H]aspartate as compared to normal conditions. Hypoglycemia or anoxia alone affected the release only marginally. The ischemia-induced induced increase in the evoked D-[3H]aspartate release was shown to be calcium-dependent. In astrocytes no difference was found in the potassium-induced release between the four conditions and the K+-induced release was not calcium-dependent. The uptake of D-[3H]aspartate was found to be stimulated at high potassium in both glutamatergic neurons (98%) and in astrocytes (70%). This stimulation of D-aspartate uptake, however, was significantly reduced under conditions of anoxia or "ischemia" in both cell types. In glutamatergic neurons (but not in astrocytes) hypoglycemia also decreased the potassium stimulation of D-aspartate uptake. In a previous report it was shown, using the microdialysis technique, that during transient cerebral ischemia in vivo the extracellular glutamate content in hippocampus was increased eightfold. In the present paper it is shown that essentially no increase in extracellular glutamate is seen under ischemia when the perfusion is performed using calcium-free, cobalt-containing perfusion media. The results from the in vitro and in vivo experiments indicate that the glutamate accumulated extracellularly under ischemia in vivo originates from transmitter pools in glutamatergic neurons.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cellular origin of ischemia-induced glutamate release from brain tissue in vivo and in vitro. 286 Feb 6

The effects of cerebral ischemia, induced for 10 min by bilateral common carotid ligation in the Mongolian gerbil, on the brain and synaptosomal content of phospholipids and free fatty acids were measured. Moreover, the incorporation of arachidonic acid and oleoyl-CoA into phospholipids, as well as the respiration and the accumulation of 45Ca, norepinephrine, dopamine, choline, glutamate, and gamma-aminobutyrate in the ischemic brain synaptosomal fraction were studied. Analyses of lipids showed a drop in phospholipids content with concomitant increase of lysocompounds and free fatty acids in ischemic cerebral cortex. Disturbances in lipid metabolism including rapid phospholipids hydrolysis and changes in the incorporation of arachidonic acid into inositol and choline phosphoglycerides were also shown in the synaptosomal fraction of ischemic brain. The uptake of neurotransmitter substances, expressed as a percent of control value, was reduced 21% for norepinephrine, 40% for dopamine, 20% for choline, 24% for glutamate and 13% for gamma-aminobutyrate in ischemic synaptosomes. There was no significant effect of ischemia on synaptosomal respiration and 45Ca uptake in both control and high potassium media. The inhibition of neurotransmitter uptake in ischemic brain synaptosomes may be caused by the disturbance of fatty acid metabolism.
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PMID:Metabolic disturbances of synaptosomes isolated from ischemic gerbil brain. 286 77

In the ventricular cerebrospinal fluid (vCSF) of 10 hydrocephalic patients the mean (+/- S.D.) concentrations of glutamate and asparate were 2.9 +/- 0.2 and 0.2 +/- 0.2 microM, respectively. Significantly higher concentrations of these amino acids were found in two patients (glutamate 37.8 and 22.4 microM, aspartate 2.2 and 0.6 microM) with symptoms of impaired brain tissue perfusion, i.e. relative ischemia due to severely increased intraventricular CSF pressure. Our results are consistent with recent experiments in rats showing increased extracellular concentrations of glutamate and aspartate during transient cerebral ischemia.
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PMID:Elevated concentrations of glutamate and aspartate in human ventricular cerebrospinal fluid (vCSF) during episodes of increased CSF pressure and clinical signs of impaired brain circulation. 286 76

Hippocampal CA-1 pyramidal cell damage was produced by 20 min of cerebral ischemia. Colchicine destruction of the dentate gyrus granule cells 11 days before ischemia prevented the CA-1 cell loss. It is suggested that the protective effect of degranulation on ischemic CA-1 pyramidal cell damage is due to reduction of glutamate release in CA-1 during and after ischemia.
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PMID:Ischemic CA-1 pyramidal cell loss is prevented by preischemic colchicine destruction of dentate gyrus granule cells. 287 69


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