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

A population of neurons localized to a small region of the brain stem reticular formation, the rostral ventrolateral reticular nucleus (RVL), is the principal area of the brainstem regulating resting, reflex, and probably behaviorally coupled control of arterial pressure. The critical area of the RVL reticular nucleus engaged in cardiovascular control surrounds a cluster of adrenergic neurons of the C1 group, and is therefore designated the C1 area. C1 area neurons have a direct and extremely potent synaptic relationship with preganglionic sympathetic neurons of the intermediolateral (IML) nucleus of the spinal cord. Neurons in the C1 area are tonically active and fire in relationship to the cardiac cycle, a rhythm imposed by baroreceptors. They thereby provide the background of excitation to preganglionic neurons to maintain normal resting arterial pressure. Which transmitter released by C1 area neurons produces sympathetic excitation is uncertain, but it may be glutamate. C1 area neurons are critical to the integration of a wide range of cardiovascular reflexes, including the arterial pressure responses to arterial baroreceptor, chemoreceptor, and other cardiopulmonary receptor stimulation, to pain and possibly to exercise, to brain stem ischemia and distortion, and probably to the arterial pressure elevations associated with emotional behavior. The cardiovascular neurons of the C1 area are responsive to the actions of a number of neurotransmitters, many of which are confined to local circuit neurons in the region, including gamma-aminobutyric acid (GABA), catecholamines, acetylcholine, and several opiates. They also appear to be the site of action upon arterial pressure of a number of drugs--including clonidine and possibly the beta-blockers. Neurons of the C1 area of the RVL reticular nucleus, therefore, appear to function as one of the most critical output systems of the brain for regulating arterial pressure in health and sickness.
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PMID:The C1 area of the rostral ventrolateral medulla oblongata. A critical brainstem region for control of resting and reflex integration of arterial pressure. 257 88

Bilateral transient occlusion of carotid arteries in gerbils for 7 min results in delayed neuronal cell death in hippocampal field CA1. Local gamma-aminobutyric acid (GABA)ergic neurons survive the ischemic insult. Here we show that interneurons in gerbil hippocampus are parvalbumin-immunoreactive, that they contain the GABA-synthetizing enzyme glutamic acid decarboxylase (GAD), and that they are resistant to the effects of ischemia, being present up to 28 days after the insult. It might be concluded that the presence of the Ca2+-binding protein parvalbumin protects the GABAergic neurons from the deleterious consequences of ischemia-induced excitotoxin-mediated Ca2+-influx.
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PMID:GABAergic hippocampal neurons resistant to ischemia-induced neuronal death contain the Ca2(+)-binding protein parvalbumin. 259 13

Proton nuclear magnetic resonance (NMR) spectroscopy of perchloric acid tissue extracts has been used to follow serial postischemic changes in the levels of metabolites in the hippocampus, cerebellum, frontal lobes, and parietal/occipital lobes in a rat model of short-duration (10 minutes) forebrain ischemia. Shortly (10 minutes, 1 hour) after the ischemic insult, the levels of the amino acids alanine and gamma-aminobutyric acid are elevated and that of glutamate is depressed in all regions except the cerebellum. The levels of these species return to control values by 24 hours postischemia. No changes are observed in the levels of aspartate or N-acetylaspartate. Greatly elevated levels of acetate 10 minutes postischemia, particularly in the hippocampus, may be due in part to metabolic degradation of fatty acids released due to membrane breakdown. Elevated levels of lactate persist for up to 7 days postischemia, suggesting that normal mitochondrial functioning is not fully restored following the ischemic insult.
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PMID:Nuclear magnetic resonance study of regional metabolism after forebrain ischemia in rats. 271 4

The release of D-[3H]aspartate (used as a tracer for endogenous glutamate and aspartate) was studied at high K+ (100 mM) and under ischemia in rats implanted with 0.3 mm diameter dialysis tubing through the hippocampus. The effect on the D-[3H]aspartate release of the two gamma-aminobutyric acid (GABA) agonists 4,5,6,7-tetrahydroisoxazolo[5,4-c]-pyridin-3-ol (THIP) and (+/-)-beta-(p-chlorophenyl)GABA (baclofen), which specifically activate GABAA and GABAB receptors, respectively, was studied. Initial experiments employing HPLC analysis showed a coincident increase in the amounts of glutamate, aspartate and the amount of radioactivity following introduction of K+ (100 mM) or a period of ischemia suggesting that the D-[3H]aspartate labels the transmitter pools of the two amino acids under the present experimental conditions. The presence of 10 mM baclofen or 10 mM THIP in the perfusion medium did not inhibit ischemia induced D-[3H]aspartate release. On the contrary, 10 mM baclofen alone (but not 0.1 or 1 mM) in the perfusion medium induced release of D-[3H]aspartate in a calcium dependent manner, whereas 10 mM THIP had no significant releasing effect.
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PMID:Baclofen-induced, calcium-dependent stimulation of in vivo release of D-[3H]aspartate from rat hippocampus monitored by intracerebral microdialysis. 276 67

Using an antibody directed against the gamma-aminobutyric acid (GABA)-synthetizing enzyme glutamate decarboxylase (GAD) the fate of the GABAergic innervation was investigated in the hippocampal field CA1 of gerbils up to 14 days after a bilateral transient 5-min occlusion of carotid arteries. As described previously, the CA1 pyramidal cells were subject to the ischemia-induced delayed neuronal death, the first signs of which were detectable after 2 days and which was fully developed after 4 days. Local GAD-immunoreactive neurons and boutons, however, exhibited no changes in their distribution and morphology over the whole 14-day period investigated, as studied both at the light and electron microscopic level. Thus, it can be assumed that the increased excitation observed during the development of delayed neuronal death, is not due to a loss of GABAergic neuronal profiles. The resistance of the GABAergic neurons to the ischemic insult is discussed in relation to the presence of Ca2+-binding proteins in this class of neurons, and the long persistence of innervation in an area nearly devoid of postsynaptic targets is considered.
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PMID:Preservation of GABAergic perikarya and boutons after transient ischemia in the gerbil hippocampal CA1 field. 276 29

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 progressive course of hepatic encephalopathy developing in rats after massive hepatic ischemia due to hepatic artery ligation within 48 hr of a portacaval shunt was not altered by the injection of a benzodiazepine antagonist, CGS 8216, in a dose that was sufficient to reverse diazepam-induced coma quickly. The onset of hepatic coma was shortened 20 to 25% by the antagonist, rather than being delayed, as would be expected if hepatic coma were due to a gamma-aminobutyric acid (GABA)-ergic effect. The neural binding of GABA by brains from rats in deep hepatic coma was unaffected by the injection of the benzodiazepine antagonist.
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PMID:A benzodiazepine antagonist does not alter the course of hepatic encephalopathy or neural gamma-aminobutyric acid (GABA) binding. 285 Apr 57

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

We have previously described a marked attenuation of postischemic striatal neuronal death by prior substantia nigra (SN) lesioning. The present study was carried out to evaluate whether the protective effect of the lesion involves changes in the degree of local cerebral blood flow (ICBF) reduction, energy metabolite depletion, or alterations in the extracellular release of striatal dopamine (DA), glutamate (Glu), or gamma-aminobutyric acid (GABA). Control and SN-lesioned rats were subjected to 20 min of forebrain ischemia by four-vessel occlusion combined with systemic hypotension. Levels of ICBF, as measured by the autoradiographic method, and energy metabolites were uniformly reduced in both the ipsi- and contralateral striata at the end of the ischemic period, a finding implying that the lesion did not affect the severity of the ischemic insult itself. Extracellular neurotransmitter levels were measured by microdialysis; the perfusate was collected before, during, and after ischemia. An approximately 500-fold increase in DA content, a 7-fold increase in Glu content, and a 5-fold increase in GABA content were observed during ischemia in nonlesioned animals. These levels gradually returned to baseline by 30 min of reperfusion. In SN-lesioned rats, the release of DA was completely prevented, the release of GABA was not affected, and the release of Glu was partially attenuated. However, excessive extracellular Glu concentrations were still attained, which are potentially toxic. This, taken together with the previous neuropathological findings, suggests that excessive release of DA is important for the development of ischemic cell damage in the striatum.
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PMID:Effect of ischemia on the in vivo release of striatal dopamine, glutamate, and gamma-aminobutyric acid studied by intracerebral microdialysis. 290 96

A series of putative neuroprotective agents was tested to determine their efficacy in preventing the loss of the CA 1 neurons of the hippocampus at 4 days following 5 min of bilateral ischemia in the gerbil. Agents associated with the GABAergic system were determined to be the most effective, but only when given prior to the ischemic episode, suggesting that there was a gamma-aminobutyric acid (GABA)-related event during ischemia which triggers the delayed neuronal death of these cells. In this report, the unidirectional release of GABA and glutamate from gerbil hippocampal slices was determined under conditions mimicking anoxia and/or ischemia. Pentobarbital, the most effective of the GABAergic agents, had little or no effect on the time-dependent release of glutamate. In contrast, pentobarbital reduced in release of GABA in both anoxia and ischemia, but only after 25 to 30 min of incubation.
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PMID:A role for gamma-aminobutyric acid (GABA) in the evolution of delayed neuronal death following ischemia. 290 68


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