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

Sodium-independent binding of [3H]gamma-aminobutyric acid ([3H]GABA) to membranes prepared from ischemic-damaged rat striatum was studied by kinetic and time-course analysis. Three days after 40 min of ischemia, [3H]GABA binding increased fourfold over control values. Scatchard analysis of the binding showed that ischemia significantly increased the affinity (KD) and the total number of binding sites (Bmax) for the high-affinity GABA receptor. These results support the conclusion that transient forebrain ischemia damages striatal GABAergic neurons.
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PMID:Increased binding of [3H]GABA to striatal membranes following ischemia. 630 Mar 37

Glycolytic substrates and metabolites (glycogen, glucose, glucose-6-phosphate, pyruvate, lactate), tricarboxylic acid cycle intermediates (citrate, alpha-ketoglutarate, succinate, fumarate, malate), related amino acids (glutamate, glutamine, alanine, gamma-aminobutyrate) and energy mediators (ATP, ADP, AMP, creatine phosphate) were evaluated in the cerebral cortex of rats after 5 min of complete compression ischemia as well as after 3, 15 or 30 min of recirculation following 5 min ischemia. The post-ischemic recovery was studied in control animals or in animals treated (30 min before ischemia and during discovery) by intravenous perfusion of vincamine, theophylline, dihydroergocristine and alanine. Interrelated changes of intermediates of the carbohydrate and the amino acid metabolism have been observed. It is concluded that alanine perfusion induced a partial detour of the lactacid anaerobic process towards the succinate-related alactacid cycle, leading to an increase in the cortical gamma-aminobutyrate content. Vincamine and dihydroergocristine acted in the opposite direction.
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PMID:Drug interference on some biochemical parameters of rat cerebral cortex during post-ischemic recovery. 677 99

Some metabolites (glycogen, glucose, glucose-6-phosphate, pyruvate, lactate, citrate, alpha-ketoglutarate, succinate, fumarate, malate, glutamate, aspartate, gamma-aminobutyrate, glutamine, alanine, NH+4) were measured in rat cerebral cortex after 5 minutes of complete compression ischemia, as well as after 5, 15, or 30 minutes of recirculation following 5 minutes of ischemia. Complete ischemia induced a drop of glycolytic substrates and intermediates, consistent with the increase of lactate, succinate, alanine, and gamma-aminobutyrate, and with the decrease of malate, fumarate, and alpha-ketoglutarate. These events may be regarded as an expression of the activation of the gamma-aminobutyrate cycle and of the succinate cycle, where succinate itself, in the absence of O2, acts as a terminal electron acceptor. During post-ischemic recovery, cerebral parameters tended to normalize, except for the further increase of alanine and the still higher than normal content of both succinate and gamma-aminobutyrate, as an expression of the possible activation of the gamma-glutamyl and gamma-aminobutyrate cycles during recovery.
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PMID:Relationships between gamma-aminobutyrate and succinate cycles during and after cerebral ischemia. 709 4

Profound hypothermia induced with cardiopulmonary bypass has a protective effect on spinal cord function during operations on the thoracoabdominal aorta. The mechanism of this protection remains unknown. It has been proposed that the release of excitatory amino acids in the extracellular space plays a causal role in irreversible neuronal damage. We investigated the changes in extracellular neurotransmitter amino acid concentrations with the use of in vivo microdialysis in a swine model of spinal cord ischemia. All animals underwent left thoracotomy and right atrium-femoral artery cardiopulmonary bypass with additional aortic arch perfusion. Lumbar laminectomies were then done and microdialysis probes were inserted stereotactically in the anterior horn of the second and fourth segments of the lumbar spinal cord. The probes were perfused with artificial cerebrospinal fluid at a rate of 2 microliters/min and 15-minute samples were assayed by high-performance liquid chromatography. Group 1 animals (n = 6) underwent aortic clamping distal to the left subclavian artery and proximal to the renal arteries for 60 minutes at normothermia (37 degrees C) and group 2 animals (n = 5) were cooled to a rectal temperature of 20 degrees C before application of aortic clamps, maintained at this level during cardiopulmonary bypass until the aorta was unclamped, and then slowly rewarmed to 37 degrees C. Seven amino acids were studied, including two excitatory neurotransmitters (glutamate and aspartate) and five putative inhibitory neurotransmitters (glycine, gamma-aminobutyric acid, serine, adenosine, and taurine). Glutamate exhibited a threefold increase in extracellular concentration during normothermic ischemia compared with baseline values and remained elevated until 60 minutes after reperfusion. The increase in aspartate concentration was not significant. The extracellular concentrations of glycine and gamma-aminobutyric acid also increased significantly during ischemia and reperfusion. Hypothermia uniformly prevented the release of amino acids in the extracellular space. Glutamate levels remained significantly decreased even after rewarming to normothermia whereas glycine levels returned to baseline values. These results are consistent with a role for excitatory amino acids in the production of ischemic spinal cord injury and suggest that the mechanism of hypothermic protection may be related to decreased release of these amino acids in the ischemic spinal cord.
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PMID:Profound systemic hypothermia inhibits the release of neurotransmitter amino acids in spinal cord ischemia. 1004 38

The effects of intravitreal injections of excitatory amino acid receptor antagonists have been studied on the ischemic neuronal damage induced by photochemical occlusion of the retinal vessels. Rats were systemically injected with rose bengal fluorescein dye and one of their eyes was exposed to bright light. The activities of the enzymes, choline-acetyltransferase and glutamate decarboxylase, were measured as an index of neuronal loss in the lesioned tissue. Lesioned retinas had a 75 +/- 5% reduction in choline-acetyltransferase activity and a 72 +/- 8% reduction in glutamate-decarboxylase activity, suggesting that the lesion causes a massive loss of retinal neurons, which use acetylcholine or gamma-aminobutyric acid (GABA) as neurotransmitter. A single intravitreal injection of excitatory amino acid receptor antagonists, performed immediately after the lesion, significantly reduced this loss. Both alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) and N-methyl-D-aspartate) (NMDA) types of ionotropic glutamate receptor antagonists were active in a dose-dependent manner. Almost complete protection was also obtained with relatively large doses of thiokynurenic acid (400 nmol), a non-selective antagonist of both AMPA and NMDA glutamate receptors, while 7-Cl-thiokynurenic acid, a potent and selective glycine receptor antagonist, was not active up to 200 nmol. These results strongly suggest that excitotoxic mechanisms are involved in ischemia-induced neuronal death in the retina and that appropriate treatments with antagonists of both AMPA and NMDA receptor types may significantly reduce this damage.
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PMID:Glutamate receptor antagonists protect against ischemia-induced retinal damage. 770 49

The aim of this study was to determine the time course of changes in extracellular fluid (ECF) concentrations of purines, amino acids, monoamines, and their metabolites in the striatum of rats during ischemia and reperfusion, using intracerebral microdialysis as the sampling technique. In rats subjected to 20 min forebrain ischemia by four-vessel occlusion, the concentrations of adenosine (Ade), inosine (Ino) and hypoxanthine (Hyp) were found to rise markedly. These changes were accompanied by dramatically elevated levels of aspartate (Asp), glutamate (Glu), taurine (Tau), gamma-aminobutyric acid (GABA), dopamine (DA) and norepinephrine (NE), all of which gradually returned to baseline following reperfusion. Concomitantly, the levels of metabolite 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), 5-hydroxyindole-3-acetic acid (5-HIAA) and xanthine (Xan) decreased during ischemia and gradually recovered 60-90 min after reperfusion. It was concluded that during global brain ischemia, the ECF is flooded with both potentially harmful (e.g. Asp, Glu, DA) and protective (e.g. Tau, GABA, Ade) agents.
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PMID:Changes of monoamines, purines and amino acids in rat striatum as measured by intercerebral microdialysis during ischemia/reperfusion. 771 61

In order to investigate changes in energy metabolism, neurotransmitters, and membrane disorder accompanying incomplete cerebral ischemia, a bilateral common carotid artery occlusion model of spontaneously hypertensive rats was utilized. We measured concentrations of ATP, phosphocreatine (PCr), lactate (Lac), glucose (Glu), acetylcholine (ACh), choline (Ch), and gamma-aminobutyric acid (GABA) in both the cerebral cortex and the subcortical regions after 1 h ischemia, 2 h ischemia, and 2 h reflow following 2 h ischemia, and then examined changes in concentrations of these substances during and after incomplete cerebral ischemia. Also, examined were interrelations of changes in these substance levels during ischemia. In the cerebral cortex, levels of ATP, PCr, Glu, and ACh decreased, and levels of Lac, Ch, and GABA increased during ischemia. After recirculation, levels of ATP, PCr, Ch, and GABA tended to return to the normal range. On the other hand, the Lac level remained in the ischemic range and the Glu level rose and greatly exceeded the normal range. With regard to ACh, most animals showed normal levels but some exceeded the normal range. Changes in the subcortical regions were qualitatively the same as those in the cerebral cortex during and after ischemia (except with Glu), but only smaller in degrees. Glu levels remained unchanged during ischemia. Correlation of the levels of these substances in the cerebral cortex was examined using normal and ischemic values. A high correlation was generally observed between ATP and other substance levels. The relations between ATP and either PCr or Glu levels were linear. The relation between ATP and ACh levels was logarithmic.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Changes in brain energy metabolism, neurotransmitters, and choline during and after incomplete cerebral ischemia in spontaneously hypertensive rats. 773 55

Preconditioning with sublethal ischemia protects against neuronal damage after subsequent lethal ischemic insults in hippocampal neurons. A pharmacological approach using agonists and antagonists at the adenosine A1 receptor as well as openers and blockers of ATP-sensitive K+ channels has been combined with an analysis of neuronal death and gene expression of subunits of glutamate and gamma-aminobutyric acid receptors, HSP70, c-fos, c-jun, and growth factors. It indicates that the mechanism of ischemic tolerance involves a cascade of events including liberation of adenosine, stimulation of adenosine A1 receptors, and, via these receptors, opening of sulfonylurea-sensitive ATP-sensitive K+ channels.
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PMID:Essential role of adenosine, adenosine A1 receptors, and ATP-sensitive K+ channels in cerebral ischemic preconditioning. 775 61

Preconditioning of the brain with sublethal ischemia induces tolerance to subsequent longer periods of ischemia. To elucidate the role of excitatory and inhibitory amino acids in the induction of ischemic tolerance, we measured the extracellular concentrations of the amino acids in the gerbil hippocampus with intracerebral microdialysis. Mongolian gerbils were subjected to 3 min of forebrain ischemia 4 days after preconditioning with 2 min of ischemia or sham operation. Microdialysis probes were implanted into the hippocampus before the second ischemia and the amino acid concentrations in the dialysates were measured with HPLC. During and immediately after 3 min of ischemia without preconditioning, the concentrations of glutamate, glycine, gamma-aminobutyric acid, and taurine, but not glutamine, increased significantly. The increased amino acid levels rapidly returned to baseline after reperfusion. Preconditioning of the brain did not alter the amount of any amino acid released during and after the second ischemia. The excitotoxic index also unchanged in the preconditioned hippocampus. Thus, the results clearly show that ischemic tolerance is not induced through the alteration of the amounts of excitatory and inhibitory amino acids released during subsequent ischemia.
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PMID:Ischemic tolerance and extracellular amino acid concentrations in gerbil hippocampus measured by intracerebral microdialysis. 781 5

Following cerebral ischemia, certain populations of neurons degenerate. Excessive accumulation of excitatory amino acids in the synaptic cleft, activation of excitatory amino acid receptors, and influx of calcium into neurons play a key role in the development of ischemia-induced neuronal death. We hypothesized that neuroprotection may be achieved by enhancing inhibitory (i.e., gamma-aminobutyric acid, GABA) neurotransmission to offset excitation. Diazepam, a drug that increases GABA-induced chloride channel opening, was administered (10 mg/kg, i.p.) to rats 1 and 2 hr following 15 min of transient global ischemia, when hippocampal GABA levels, increased during ischemia, returned to basal. Rats were maintained normothermic during ischemia and became hypothermic following the injections of diazepam. Four days later, rats were sacrificed and the brains were examined for neuronal degeneration and the presence of GABAA receptors labeled by 35S-t-butylbicyclophosphorothionate (35S-TBPS). There was substantial neuroprotection of striatal neurons and pyramidal neurons in the CA1 area of the hippocampus. In addition, diazepam prevented the loss of 35S-TBPS binding sites in the striatum and in the dendritic fields of the CA1 hippocampus following ischemia. Since hypothermia, itself, is neuroprotective, we determined if hypothermia was required for the ability of diazepam to produce neuroprotection. Diazepam was microinjected into the CA1 hippocampus 1 and 2 hr following ischemia, and rats remained normothermic. Four days later, diazepam still produced substantial protection of hippocampal neurons. Thus, postischemic hypothermia may have contributed to the neuroprotection by diazepam when it was administered systemically, but the neuroprotective effect of diazepam did not require hypothermia. We conclude that delayed enhancement of GABAergic neurotransmission directly at the site of vulnerability following an ischemic event protects the vulnerable neurons from death.
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PMID:Diazepam, given postischemia, protects selectively vulnerable neurons in the rat hippocampus and striatum. 782 61


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