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

GABAergic neurons in the striatum are very sensitive to the effects of ischemia. The progressive decline in striatal GABA following transient forebrain ischemia in gerbils may be secondary to either a decreased production or an increase in reuptake mechanisms or both. The current experiment was designed to evaluate release of GABA by stimulation with K+ or inhibition of its uptake with nipecotic acid or their combination (K+ nipecotic) after repetitive forebrain ischemia in gerbils by in-vivo microdialysis on Days 1, 3, 5, and 14 following the insult. Infusion of nipecotic acid or potassium chloride, resulted in a significant increase in extracellular GABA. This response was significantly decreased in the post-ischemic animals. The synergistic effect of increased GABA concentrations by the infusion of nipecotic acid + potassium chloride seem in the controls was not evident in the post-ischemic animals. In conclusion, though there is a reduction in the extracellular GABA concentrations in the first week following an ischemic insult, restorative mechanisms are operative in the second week as seen by the increasing GABA concentrations.
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PMID:GABA concentrations in the striatum following repetitive cerebral ischemia. 858 54

The study was aimed at the analysis of vulnerability of the olfactory bulb neurons in dogs after experimental heart arrest lasting for 15 minutes and recirculation lasting for 1 hour. By means of the Nauta degenerative neurohistologic method the reactions of individual types of nerve cells in the olfactory bulb were investigated. Nauta-positive granules were observed in the cytoplasm of the mitral and tufted cells of the olfactory bulb, which are of dopaminergic character. The granulations were present in the cellular areas which are rich in Nissl substance. The granular and short-axon cells of GABA-ergic character which contain a small amount of Nissl granules lack the Nauta-positive granules. Similarly, the Nauta-positive granules were absent in the axon hillock of mitral cells which under normal conditions do not contain the Nissl substance. These results justify the conclusion that ischemia lasting for 15 minutes and one-hour recirculation primarily affect the excitatory neurons rich in the Nissl substance. (Fig. 4, Ref. 16.).
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PMID:[Selective vulnerability of neuronal injury after experimental heart arrest]. 862 50

The aim of this study was to elucidate the mechanisms by which retinal cells release endogenous amino acids in response to ascorbate/Fe(2+)-induced oxidative stress, as compared with chemical hypoxia or ischemia. In the absence of stimulation, oxidative stress increased the release of aspartate, glutamate, taurine, and GABA only when Ca2+ was present. Under hypoxia or ischemia, the release of aspartate, glutamate, glycine, alanine, taurine, and GABA increased mainly by a Ca(2+)-independent mechanism. The increased release observed in N-methyl-D-glucamine+ medium suggested the reversal of the Na+-dependent amino acid transporters. Upon oxidative stress, the release of aspartate, glutamate, and GABA, occurring through the reversal of the Na(+)-dependent transporters, was reduced by about 30%, although the release of taurine was enhanced. An increased release of [3H]arachidonic acid and free radicals seems to affect the Na+-dependent transporters for glutamate and GABA in oxidized cells. All cell treatments increased [Ca2+]i (1.5 to twofold), although no differences were observed in membrane depolarization. The energy charge of cells submitted to hypoxia or oxidative stress was not changed. However, ischemia highly potentiated the reduction of the energy charge, as compared with hypoglycemia or hypoxia alone. The present work is important for understanding the mechanisms of amino acid release that occur in vivo upon oxidative stress, hypoxia, or ischemia, frequently associated with the impairment of energy metabolism.
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PMID:Oxidative stress, hypoxia, and ischemia-like conditions increase the release of endogenous amino acids by distinct mechanisms in cultured retinal cells. 863 76

In the dentate gyrus, granule cells are ischemia-resistant, but at least five types of predominantly spiny hilar neurons are extremely vulnerable to ischemia. Many of the ischemia-sensitive subtypes of hilar neurons appear to be involved in: (i) the regulation of GABAergic inhibition in the dentate gyrus, and (ii) the generation of hilar neuronal synchrony. The present study examined functional consequences of ischemia-induced hilar neuronal loss on GABAergic inhibition of granule cells and hilar neuronal synchrony. Transient (15 min) forebrain ischemia was induced by a modification of the four-vessel-occlusion method producing a substantial hilar neuronal loss as demonstrated by the Gallyas silver stain method. Three months later, we have examined spontaneous and stimulus-evoked inhibitory postsynaptic currents mediated by both GABA(A) and GABA(B) receptors, and inhibitory bursts induced by 4-aminopyridine (50 microM) using whole-cell recordings in coronal brain slices maintained at 34-36 degree C in the presence of excitatory amino acid receptor blockers. Spontaneous dentate spikes reflecting hilar neuronal synchrony and synaptic responses evoked by perforant path stimulation were also recorded in vivo to assess synchrony and inhibition in the dentate gyrus. In spite of significant damage to several types of hilar neurons, there were no marked differences in the conductance, kinetics, and 4-aminopyridine-induced burst frequencies of synaptic GABA(A) and GABA(B) responses in granule cells. Furthermore, both paired-pulse inhibition and dentate spikes appeared to be normal in vivo. We conclude that there appears to be little impairment of GABAergic inhibition of granule cells or of hilar neuronal synchrony three months following a massive ischemic damage to spiny hilar neurons.
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PMID:GABAergic inhibition of granule cells and hilar neuronal synchrony following ischemia-induced hilar neuronal loss. 863 12

The subcellular distribution of glutamate and GABA in synapses of Mongolian gerbils hippocampus was examined using post-embedding immunogold staining method for electron microscopy. Immunolabelling was performed with 10 nm gold-antibody complexes for glutamate and GABA. The gold particle densities gave reliable information about the relative concentrations of these amino acid neurotransmitters. Our results indicate that ischemia leads to the temporal decrease of GABA-like immunoreactivity in symmetric synapses and a slight enhancement of the level of glutamate-like reactivity in asymmetric ones. The striking finding was a redistribution of glutamate-like immunoreactivity from neurons to glia. This suggests the capacity of glia to metabolize the excess of glutamate after ischemia. The disturbances at the level of neurotransmitters and their possible role in hippocampal neuronal injury were stressed.
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PMID:Immuno-electron microscopic demonstration of GABA and glutamate synapses in Mongolian gerbils hippocampus after ischemia. 867 20

We are applying multi-nuclear high-field (500 MHz) MR spectroscopy of metabolising whole tissue preparations of the mammalian brain to studies on individual components of convulsions, which include prolonged depolarization, metabolic deprivation, and the effects of excitotoxins. The responses of glial cells and neurones can be partially distinguished by following labelling patterns of metabolic intermediates from 13C-labelled glucose or acetate (which enters only glial cells). This approach clearly confirmed our earlier indications that the metabolic response to depolarization (40 mM extracellular K+) occurs essentially in glial cells. Some evidence for metabolic shuttling between glia and neurones was obtained from the changes in C3/C4 ratios of glutamate and glutamine, and the C2/C3 of GABA. Mechanisms for metabolic support of neurones by glia may be of importance in neuronal protection under such metabolic stress as occurs in epilepsy. Changes in free intracellular divalent cations ([Ca2+]i and [Zn2+]i) were monitored using the 19F-MRS indicator, 5FBAPTA. Large increases in [Ca2+]i and decreases in PCr were produced by excitotoxins (glutamate and NMDA), depolarization or ischemia, but intracellular Zn2+ appeared only after exposure to the excitotoxins. The NMDA receptor blocker, MK801, removed all of the responses to NMDA, but only prevented the appearance of Zn2+ observed with glutamate. These results indicate that the damage caused to neurones by such insults as convulsions is not due simply to the presence of excessive excitotoxic glutamate.
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PMID:High-field MRS studies in brain slices. 875 Mar 39

In order to investigate changes in levels of monoamines and their related substances together with those of other neurotransmitters (acetylcholine and GABA), choline and substances related to energy metabolism (ATP, lactate and glucose) accompanying incomplete cerebral ischemia, a bilateral common carotid artery occlusion model of spontaneously hypertensive rats (SHR) was utilized. Animals were subjected to 1 or 2 h ischemia. Then the concentrations of substances were measured in the cerebral cortex, hippocampus and striatum and compared with control values. Due to the incomplete ischemia, ATP showed a moderate decrease, while lactate and choline increased remarkably, and GABA underwent a moderate increase. With regard to monoamines, both noradrenaline and serotonin levels were reduced in the cerebral cortex and hippocampus, whereas dopamine levels increased in the hippocampus. All monoamine metabolites, i.e. metabolites by monoamine oxidase (MAO), metabolites by catechol-O-methyltransferase (COMT), and metabolites by both MAO and COMT, underwent increases. The 3-methoxytyramine level in particular showed marked increases. Furthermore levels of precursor amino acids as well as 5-hydroxytryptophan rose. Acetylcholine decreased moderately only in the cerebral cortex. Among these changes, sustained increases in all the monoamine metabolites were characteristic of changes in the incompletely ischemic brain, suggesting that both COMT and MAO retain their activities in the incompletely ischemic brain.
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PMID:Changes in levels of monoamines and their metabolites in incompletely ischemic brains of spontaneously hypertensive rats. 878 4

The authors conducted an in vivo study, using a rat striatal ischemic model, of the effect of GABAergic transmission upon the dopamine synthesizing enzyme tyrosine hydroxylase in the neurons of the substantia nigra pars compacta. Two hours transient middle cerebral artery occlusion produced massive striatal ischemic damage resulting in a marked decrease of GABAergic projection to the ipsilateral substantia nigra. Histological examinations were conducted in rats killed at three, seven, 15, 30 and 94 days after ischemia. The immunoreactivity for tyrosine hydroxylase in the ipsilateral pars compacta was unaltered up to three days after the ischemic insult, but it was markedly decreased at seven days post-ischemia. At this stage, the number of neurons positive for tyrosine hydroxylase was significantly decreased in the ipsilateral pars compacta, whereas there was no significant reduction in the number of pars compacta neurons containing Nissl substance. By 30 days post-ischemia, the tyrosine hydroxylase-positive cell number in the ipsilateral pars compacta appeared to be equivalent to that of the contralateral side. It was also noted that continuous intraventricular administration of a GABAA receptor agonist muscimol, initiated from 24 h post-ischemia, effectively prevented the transient reduction of immunoreactivity for tyrosine hydroxylase in the ipsilateral pars compacta at seven and 15 days after ischemic insult. The present study revealed that the striatal ischemic lesion induced a transient down-regulation of tyrosine hydroxylase synthesis in the pars compacta neurons, which could be prevented by administration of GABA agonist, suggesting that GABAergic transmission greatly affects dopamine metabolism in these cells.
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PMID:Gabaergic transmission and tyrosine hydroxylase expression in the nigral dopaminergic neurons: an in vivo study using a reversible ischemia model of rats. 880 97

The use of glutamate antagonists and GABA agonists may protect neurons from the effects of transient ischemia. Felbamate is a new antiepileptic drug with glutamate antagonist and GABA agonist properties. We tested the efficacy of felbamate in a gerbil model of transient forebrain ischemia. Damage assessment was done with silver staining at 7 and 28 days after 5 min of bilateral carotid occlusion. Cerebral cortex, hippocampus (CA1 and CA4), thalamus and striatum were evaluated on a 4-point scoring system. The animals sacrificed at 28 days were also tested in a water-maze task to assess recovery of function. The initial dose of felbamate (300 mg/kg) was given 30 min before the ischemic insult in one set of animals and 30 min after the insult in another set of animals. There were 8 animals tested per group (total: 48 animals). There was significant neuronal protection with the use of felbamate, both before and after ischemia in all regions of the brain. Protection was seen in animals sacrificed at 7 and 28 days. Protection was moderate when felbamate was used before ischemia. It was highly significant when felbamate was given 30 min after the insult. Behavioral studies however did not show any difference in the felbamate treated animals versus the saline treated controls. The structural protection with felbamate was very significant when used in the post-ischemic period. This window for protection merits further evaluation in relation to the clinical setting of stroke.
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PMID:Neuroprotection with felbamate: a 7- and 28-day study in transient forebrain ischemia in gerbils. 884 83

Enhancing inhibitory mechanisms has been shown to improve neuronal survival after transient focal or global ischemia. In most studies, histological evaluations have been confined to the CA1 region of the hippocampus up to 7 days after an ischemic insult. We have previously shown that continuous intra-ventricular infusion of gamma-vinyl GABA (GVG) results in significant protection after cerebral ischemia. This present study was designed to assess histological and behavioral function at 7 and 28 days after a single 5 min ischemic episode in gerbils. One set of animals received the medication 30 min before the insult and the other set at 1 h after the insult. Evaluation at 7 days showed significant protection in most regions of the brain in both the pre- and post-ischemic treated animals in comparison to the controls. Delayed evaluation at 28 days showed significant protection only in the pre-ischemic treated animals. Behavioral testing with Morris water maze showed no differences in either pre- or post-ischemic treated animals when compared to saline-treated ischemic controls. Our study clearly demonstrates the usefulness of delayed evaluation in the assessment of 'true' neuronal protection. Pre-ischemic treated animals showed persistent and true neuronal protection, in contrast to a temporary protection as seen at 7 days in the post-ischemic treated animals. The lack of behavioral improvement in the pre- and post-ischemic treated animals suggests that morphological protection alone cannot be considered as the sole criterion for successful outcome.
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PMID:The neuroprotective effects of gamma-vinyl GABA in transient global ischemia: a morphological study with early and delayed evaluations. 892 63


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