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

1. Cerebral ischemia of 5 min duration was induced in unanesthetized gerbils by bilateral occlusion of the carotid arteries. 2. The extent of cerebral damage was assessed by the elevation of motor activity in comparison with pre-ischemic levels and by a histological assessment of the extent of neuronal degeneration of the CA1 area of the hippocampus. 3. The GABA transport inhibitor CI-966 (10 mg/kg i.p.) was tested for cerebroprotective activity in a gerbil stroke model. CI-966 reduced the extent of stroke injury as assessed by locomotor activity and measurement of hippocampal CA1 pyramidal cell injury. 4. It is proposed that enhancement of extracellular GABA levels during ischemia accounts for the cerebroprotective actions of CI-966.
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PMID:CI-966, a GABA uptake inhibitor, antagonizes ischemia-induced neuronal degeneration in the gerbil. 755 51

The effect of energy failure on Cl(-)-dependent L-glutamate (L-Glu) transport was examined with an in vitro preparation. Rat brain slices were incubated in low oxygen and glucose-deprived medium (in vitro ischemia), and a synaptic membrane fraction was prepared from the slices. Cl(-)-dependent L-[3H]Glu uptake into vesicles increased about twofold after 20 min of in vitro ischemia. The increased L-[3H]Glu uptake was inhibited by L-Glu, DL-2-amino-4-phosphonobutyrate, L-homocysteic acid, L-cystine, 4,4'-diisothiocyano-2,2'-disulfonic stilbene, and removal of Cl-. Uptakes of Na(+)-dependent L-[3H]Glu, [3H]GABA, and [3H]taurine were not changed by the in vitro ischemia. In vitro ischemia increased the Vmax value without affecting the Km value. The increased L-[3H]Glu uptake by in vitro ischemia was reduced by subsequent incubation in a normoxic glucose-containing solution. ATP content in brain slices decreased to < 10% of control values by in vitro ischemia for 10 min. The decrease in ATP content was restored by subsequent incubation in normoxic glucose-containing solution. Treatment with veratrine, 2,4-dinitrophenol, carbonyl cyanide m-chlorophenylhydrazone, and NaCN in normoxic conditions increased L-[3H]Glu uptake with a concomitant decrease in ATP content in slices. These results suggest that Cl(-)-dependent L-Glu transport activity in synaptic membranes increases in ischemia- or hypoxia-induced brain energy failures.
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PMID:Increase in chloride-dependent L-glutamate transport activity in synaptic membrane after in vitro ischemic treatment. 756 78

During transient cerebral ischemia, there is a temporary and robust accumulation of extracellular GABA in the hippocampus. We examined whether the acute exposure of GABAA/benzodiazepine receptors to high concentrations of GABA early after ischemia results in receptor down-regulation as observed in vitro. Gerbils were killed 30 and 60 min following a 5-min bilateral carotid occlusion, and their brains were prepared for receptor autoradiography. The hydrophilic, GABAA receptor antagonist [3H]SR-95531 and the hydrophobic benzodiazepine agonist [3H]flunitrazepam were used to distinguish between cell surface and internalized receptors. Ischemia significantly decreased [3H]SR-95531 binding in hippocampal areas CA1 and CA3 and in the dentate gyrus 30 min after ischemia. Scatchard analysis in area CA1 revealed that ischemia decreased the Bmax as low as 44%. The affinity of the remaining sites was increased substantially (72% decrease in KD). As expected, there were no changes in the binding of [3H]flunitrazepam to hippocampus in the early postischemic period because the benzodiazepine could bind to both internalized receptors and those on the cell surface. We hypothesize that prolonged exposure (approximately 30-45 min) of GABAA receptors to high concentrations of synaptic GABA in vivo causes receptor down-regulation, perhaps via receptor internalization.
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PMID:Rapid down-regulation of GABAA receptors in the gerbil hippocampus following transient cerebral ischemia. 759 83

Repeated episodes of cerebral hypoxia-ischemia can cause primarily striatal neuronal loss in the developing brain. We investigated the effect of repeated episodes of asphyxia on specific neuronal sub-populations of the basal ganglia in late-gestation fetal sheep. Asphyxia was induced in 10 fetal sheep (118-126 days gestation) by occluding the umbilical cord for 5 min. This procedure was repeated four times at 30 min intervals and the brains were fixed 3 days later for histopathology. Immunohistochemical markers were used to identify various populations of neurons in the striatum. Antibodies to calbindin were used to stain the GABAergic medium-sized striatal projection neurons and antibodies to somatostatin and parvalbumin to identify striatal interneurons. Striatal projection neurons to the globus pallidus were recognized by enkephalin immunoreactivity, while the striatonigral terminals were identified in the substantia nigra pars reticulata by substance P immunohistochemical labelling. The results showed a marked loss of calbindin staining in the striatum, evident by both reduced cell numbers and a decrease in neuropil staining. The number of parvalbumin immunoreactive cells was also reduced in the striatum, while somatostatin interneurons were selectively preserved. In addition, immunostaining for enkephalin in the globus pallidus and for substance P in the substantia nigra was markedly reduced. These results show that the stiatal GABAergic medium-sized projection neurons are severely affected by recurrent episodes of asphyxia. These findings are confirmed and extended by the results demonstrating that both the enkephalin/GABA striatopallidal and the substance P/GABA stiatonigral pathways are affected. The results of this study therefore suggest that the efferent striatal projections to the globus pallidus and to the substantia nigra may be involved in asphyxial episodes resulting in cerebral palsy.
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PMID:Repeated asphyxia causes loss of striatal projection neurons in the fetal sheep brain. 760 81

We report two diabetic patients with hemichorea-hemiballism associated with striatal lesions detected by MRI. Case 1 was a 57-year-old woman. On May 5, 1990, hemichorea-hemiballism of the right upper extremity developed suddenly. The blood glucose level at the time of onset was 695 mg/dl. Plain cranial CT scanning revealed a small high-density lesion in the left putamen. On MRI, this lesion showed a high signal intensity on T1-weighted images, while it showed as an irregular low-intensity area on T2-weighted images. Three and a half months later, the high intensity lesion on MRI decreased gradually and almost disappeared. Case 2 was a 68-year-old woman. In late August 1992, hemichorea-hemiballism of the right upper and lower extremities developed suddenly. The blood glucose level at the time of onset was 365 mg/dl. Plain cranial CT scanning was normal. MRI revealed a high signal intensity lesion involving the left putamen, globus pallidus and head of the caudate nucleus on T1-weighted images, while the lesion was almost isointense on T2-weighted images. The high-intensity lesion on MRI thereafter decreased gradually and disappeared almost completely one year after the onset. It is characteristic that the lesions responsible for hemichorea-hemiballism showed high-intensity areas on T1-weighted MRI in these two diabetics. In the hyperglycemic state, the Krebs cycle is inhibited and GABA is utilized as an energy source. The possibility has been suggested that striatal ischemia is likely to occur in diabetics because the GABA content of the corpus striatum is decreased by hyperglycemia.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Two diabetics with hemichorea-hemiballism and striatal lesions]. 766 16

There are reports that insulin may protect neurons from the effects of ischemia. The mechanisms for this protection are not fully understood. We studied the extracellular levels of glutamate and GABA in insulin-treated animals exposed to transient forebrain ischemia under normoglycemic and hypoglycemic conditions. In vivo microdialysis technique was used to collect extracellular fluid from the CA1 region of the hippocampus. There was a significant increase in GABA levels in the two insulin-treated sub-groups compared with the controls. GABA levels were < 1 pmol/10 microliters in three 10 min collections prior to ischemia in all the groups. It increased from 11.1 +/- 3.5 pmol/10 microliters in the conrol group to 47 +/- 5 (P < 0.001) in the insulin-treated hypoglycemic group and up to 47.2 +/- 9.3+ (P < 0.005) in the insulin-treated normoglycemic group (two-way ANOVA with repeated measures). Ischemia resulted in an increase in the glutamate levels. The glutamate levels returned to baseline within 30 min of the insult. There were no significant differences in the glutamate levels in three groups. The increase in GABA concentrations in the extracellular space may result in the inhibition of CA1 pyramidal neurons. This may be a possible mechanism of neuronal protection in animals treated with insulin (with or without being hypoglycemic) during ischemia.
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PMID:Insulin elevates hippocampal GABA levels during ischemia. This is independent of its hypoglycemic effect. 767 7

The distribution and extent of glutamate decarboxylase 65 (GAD65) mRNA-labeled neurons that coexpress pre-prosomatostatin mRNA were studied in the rat dentate gyrus of the dorsal and ventral hippocampal formation. The distribution of each group of neurons was determined initially by nonradioactive in situ hybridization experiments with digoxigenin-labeled riboprobes for GAD65 mRNA and pre-prosomatostatin mRNA. Double labeling experiments were then conducted with digoxigenin-labeled riboprobes for GAD65 mRNA and 35S-labeled riboprobes for pre-prosomatostatin mRNA. In the dorsal and ventral dentate gyrus, GAD65 mRNA-containing neurons were highly concentrated in the hilus and in the innermost part of the granule cell layer whereas only a few labeled neurons were scattered in the molecular layer. Pre-prosomatostatin mRNA-containing neurons were primarily located in the hilus and were virtually absent from the molecular and granule cell layers. The simultaneous detection of GAD65 and pre-prosomatostatin mRNAs in the same sections showed that the vast majority of pre-prosomatostatin mRNA-containing neurons in the hilus of the dentate gyrus were also labeled for GAD65 mRNA. In contrast many GAD65 mRNA-labeled neurons did not contain pre-prosomatostatin mRNA. These included all neurons in the molecular layer, neurons within the inner granule cell layer and neurons interspersed amongst double labeled neurons in the hilus. Quantitative analyses indicated that a very high percentage of hilar pre-prosomatostatin mRNA-containing neurons coexpressed GAD65 mRNA in the dorsal (96%) and ventral (92%) dentate gyrus. In contrast only a part of the total population of hilar GAD65 mRNA-containing neurons were also labeled for pre-prosomatostatin mRNA in the dorsal (43%) and ventral (53%) dentate gyrus. In the CA3c region, the percentages of neurons containing both mRNAs were similar to those observed in the hilus. The findings demonstrate that the vast majority of hilar somatostatin neurons, which have previously been shown to be extremely vulnerable to ischemia and seizure-induced damage, are GABA neurons. However, the total population of GAD65 mRNA-containing neurons in the hilus is substantially larger than the somatostatin-containing subgroup, and these findings reinforce the suggestion that GABA neurons are a major component of the diverse group of neurons in the hilus of the dentate gyrus.
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PMID:Somatostatin neurons are a subpopulation of GABA neurons in the rat dentate gyrus: evidence from colocalization of pre-prosomatostatin and glutamate decarboxylase messenger RNAs. 770 May 25

The involvement of phospholipases in ischemia-evoked release of aspartate, glutamate, glycine, and GABA from the cerebral cortex was studied in a four vessel occlusion rat model of cerebral ischemia/reperfusion. In comparison with the control group, the phospholipase A2 inhibitor mepacrine significantly decreased the ischemia-evoked efflux of transmitter amino acids into cortical superfusates. Direct application of phospholipases A2 or C to the cerebral cortex of non-ischemic animals resulted in a significant increase in amino acid levels. These results suggest that neurotransmitter release following cerebral ischemia may involve phospholipase induced plasma membrane disruption.
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PMID:A possible role for phospholipases in the release of neurotransmitter amino acids from ischemic rat cerebral cortex. 775 89

The number of GABA-like immunoreactive (LI) cells in lamina I-III of the rat spinal cord was significantly decreased bilaterally 48-72 h after photochemical induction of transient spinal cord ischemia compared to sham-operated controls. No significant changes in the number of GABA-LI cells were observed at cervical level. The number of GABA-LI cells was restored 2 weeks after ischemia. These data, together with recent behavioral and electrophysiological findings, suggest that decreased intraneuronal GABA levels after spinal cord ischemia may underlie the development of the temporary pain-like response to innocuous mechanical stimuli (allodynia) in rats after transient spinal cord ischemia.
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PMID:Decreased GABA immunoreactivity in spinal cord dorsal horn neurons after transient spinal cord ischemia in the rat. 780 36

The aim of the present study was 2-fold: (1) to determine the ratio between the amount of GAD67 and GAD65 (two isoforms of the GABA synthetizing enzyme glutamic acid decarboxylase) in nerve endings in the mature rat cerebral cortex damaged by hypoxia-ischemia during early postnatal life; and (2) to compare two different computer-assisted procedures developed for quantitative analysis of immunofluorescence images obtained with a confocal laser scanning microscope (CLSM). One procedure was based on a program present in the standard Leica CLSM software packet for full-field analysis, the other on a specially written program for object-oriented analysis run on a Kontron IBAS-KAT image analysis system. To this end, rat pups were unilaterally exposed to hypoxic-ischemic conditions and, after a survival period of 6.5 months, sacrificed by perfusion fixation. After dissection of the brain and vibratome sectioning, three animals with substantial damage on one cortical side were selected. Sections of these animals were double-stained with primary antibodies against GAD67 and GAD65 and fluorophore-conjugated secondary antibodies and subsequently sampled with a CLSM. Analysis of the CLSM images with both computer-assisted procedures showed for all three animals a clear tendency to higher GAD67/GAD65 ratios in cortical GABAergic nerve endings on the hypoxia-damaged side than in matched areas on the contralateral side. This outcome led to the following conclusions. (1) The correspondence between the outcome of both analysis procedures indicates that both procedures are valid for quantification of immunofluorescence images of nerve endings obtained with a CLSM. (2) The outcome lends further support to our view that hypoxic-ischemic encephalopathy, sustained during early postnatal life, may result in an unstable cortical network generating abnormal synchronizations and oscillations which can be amplified and propagated as true epileptic discharges. In such a network both excitatory and inhibitory processes are tonically enhanced, the latter probably as a homeostatic reaction tending to keep abnormal excitation within physiological limits.
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PMID:Quantitative immunofluorescence data suggest a permanently enhanced GAD67/GAD65 ratio in nerve endings in rat cerebral cortex damaged by early postnatal hypoxia-ischemia: a comparison between two computer-assisted procedures for quantification of confocal laser scanning microscopic immunofluorescence images. 782 Jun 25


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