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

The metabotropic glutamate receptors (mGluRs) can be classified into three families based on amino acid sequence homology, signal transduction mechanisms and pharmacological properties. Generally, class I mGluRs mediate an excitation of neurons while activation of class II and III mGluRs results in a depression of synaptic transmission. In this study we have analyzed the expression pattern of mGluRs in human hippocampus using a panel of polyclonal antibodies specific for mGluR1b, mGluR2/3, mGluR4a, and mGluR5. Immunoreactivity for mGluR1b and mGluR5, i.e., the subtypes representing class I mGluRs, was found in all hippocampal neurons. The mGluR1b antiserum stained perikarya and proximal dendrites, whereas immunoreactivity for mGluR5 was also detectable in the distal dendritic compartments. Immunoreactivity for mGluR2/3, members of class II mGluRs, was present in all principle neurons in the dentate gyrus as well as in the CA4, CA3 and CA2 regions. Pyramidal cells of the CA1 region exhibited only weak labeling for mGluR2/3. Glial cells were also mGluR2/3-immunoreactive. The reaction obtained with an antiserum directed against mGluR4a, a member of class III mGluRs, was confined to the mossy fiber projection field in CA3 stratum lucidum. These data demonstrate differential expression of mGluR variants in the human hippocampus and may provide an important basis for future studies of mGluRs under various neuropathological conditions such as temporal lobe epilepsy, ischemia and neurodegenerative disorders.
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PMID:Immunohistochemical distribution of metabotropic glutamate receptor subtypes mGluR1b, mGluR2/3, mGluR4a and mGluR5 in human hippocampus. 893 Mar 27

Wistar rats were subjected to transient forebrain ischemia for 30 min. After a survival period of two to three days their brains were fixed and sections were processed for Nauta suppressive method (26) to study postischemic degenerative changes and for glial fibrillary acidic protein (GFAP) to study glial reaction. After two days somatodendritic argyrophilia was evident in the CA1a and CA4 areas. The somata and dendrites of CA1 a pyramidal neurons were intensely argyrophilic, and a clear border zone which separated these neurons from undamaged CA1b neurons was detected. In the CA4 area a few degenerating, probably mossy cells were found. Neuronal degeneration then proceeded rapidly during a 72 h survival period, when the somata and dendrites of complete CA1 and CA2 pyramidal cells became intensively argyrophilic. The area of CA4 was full of degenerated neurons, but the CA3 neurons remained intact. Postischemic glial changes were observed after 48h survival. The rostral part of CA1a area contained a higher concentration of astrocytes in the dendritic layer as well as in the pyramidal layer. These astrocytes revealed features of reactive astrocytes. An intense GFAP immunoreactivity with heavily stained astrocytic figures appeared in the CA2, CA3 dendritic layers, stratum molecular of the DG and hilus. The central region of CA4 area contained various vacuoles with clearly stained astrocytes. By 72 h after ischemia the tissue structure changed in all areas since the pyramidal layer contained shrunken neurons and large vacuoles. The GFAP immunoreactivity in the hippocampus was the same or even higher as observed after two days postischemia, but the astrocytes were seen more closely in the relation with the pyramidal cell layer.
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PMID:Ischemic damage in the hippocampus: a silver impregnation and immunocytochemical study in the rat. 893 16

Immediate early genes are induced by transient global ischemia. Using immunohistochemistry we studied the effect of intraischemic hypothermia (30 degrees C) on the expression of c-fos and fos-B proteins following 10 min forebrain ischemia in the gerbil. Postischemia (PI) periods of 1 hour (h), 6 h, 1 day (d) and 2 d and nonischemic controls were examined in normothermic and hypothermic brains. In normothermic ischemic brains, marked expression of c-fos occurred in the dentate gyrus after 1 h PI which extended to CA2-4 regions by 6 h. Hypothermia hastened the time course of c-fos expression as it was expressed simultaneously in the dentate gyrus as well as CA2-4 regions after only 1 h, and by 6 h the expression remained only in the CA2-4 regions and not the dentate gyrus in hypothermic ischemic brains. There was no difference in its expression between normothermic and hypothermic brains in the 1 d and 2 d PI animals. Somewhat similar changes were noted in fos-B expression. In normothermic ischemic brains fos-B was induced in the dentate gyrus by 1 h PI, and by 6 h it extended to involve CA1-4 cells. The hypothermic ischemic brains showed faster induction of fos-B so that the dentate gyrus as well as CA1-4 regions were immunopositive at 1 h PI. There was no difference in its expression between normothermic and hypothermic brains in the subsequent PI periods of 6 h, 1 d and 2 d. The shift towards faster sequential induction of these genes by hypothermia in ischemic brains may be indicative of preservation of or faster recovery of mechanisms involved in intracellular signalling.
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PMID:Expression of c-fos and fos-B proteins following transient forebrain ischemia: effect of hypothermia. 901 91

Ubiquitin (Ub) is a small 76-residue protein, involved in intracellular protein degradation through a specific ATP-dependent system, which uses Ub as a tag to label proteins committed to be hydrolyzed by a specific 26 S protease. PGP-9.5 is another important component of the Ub system, i.e. a neuron-specific carboxyl-terminal hydrolase, which recycles Ub from Ub-polypeptide complexes. We have investigated the expression of Ub and PGP-9.5 in rat hippocampal neurons in an early phase of reperfusion in a model of transient global brain ischemia/hypoxia (bilateral occlusion of common carotid arteries for 10 min accompanied by mild hypoxia-15% O2-for 20 min), by means of immunohistochemical methods using light and electron microscopy. The intensity of Ub and PGP-9.5 immunoreactivity was evaluated by image analysis. We have detected a marked increase of Ub immunoreactivity (UIR) in neurons of CA1, CA2, CA3, CA4, and dentate gyrus subfields 1 hr after ischemia/hypoxia (but not after hypoxia only), statistically significant as confirmed by image analysis. Such increase in immunoreactivity in ischemic/hypoxic rats was localized essentially in the nuclei of hippocampal neurons. There were no changes in PGP-9.5 immunoreactivity. The data suggest that in the present model of rat brain ischemia/hypoxia Ub is involved in the neuronal stress response.
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PMID:Ubiquitin-mediated stress response in a rat model of brain transient ischemia/hypoxia. 902 69

Based on our previous observation that transient forebrain ischemia induces calpain-catalyzed proteolysis in gerbil hippocampus in a region-specific manner, we examined the effect of ischemia on the quantity and localization of the endogenous calpain-specific inhibitor protein, calpastatin, in the tissue. Brief (5 min) forebrain ischemia followed by reperfusion induced an overall increase of calpastatin immunoreactivity in hippocampus, particularly in pyramidal cells, in 4 h as analyzed by Western blotting and immunohistochemistry. The amount of calpastatin, however, decreased to the preischemic level and lower in 24 h to 7 days due to proteolysis except in CA2 showing continuously elevated calpastatin immunoreactivity. Because calpastatin is not only a potent inhibitor but also a preferred substrate for calpain and because CA2 neurons are less vulnerable to ischemic stress than the adjacent CA1 neurons, these observations imply involvement of calpastatin in calpain regulation as a bait substrate and, possibly, in neuroprotection under ischemic conditions. Calpastatin may participate in the stress responses together with the previously known ischemia-induced stress proteins such as heat shock proteins.
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PMID:Up- and down-regulation of calpain inhibitor polypeptide, calpastatin, in postischemic hippocampus. 918 Feb 7

In this study we sought to determine if ischemic preconditioning provided long term behavioral and histological protection. A second goal was to see if ischemic preconditioning conveys its protective effect on CA1 neurons by altering post-ischemic brain temperature. While preconditioning episodes of short duration ischemia (i.e. 1.5 min) provided significant histological protection of CA1 pyramidal cells against a subsequent severe ischemic insult (i.e. 5 min), this did not result in complete behavioural protection. Preconditioned ischemic animals initially displayed habituation deficits in an open field test that were comparable to untreated ischemic gerbils. A significant decline in CA1 preservation in preconditioned animals was observed when survival time was extended from 10 (81% protection) to 30 (53% protection) days. In addition, protection was not observed in the subiculum and CA2 sector of the hippocampus where consistent damage was observed in 21/22 gerbils. Ischemic preconditioning did not markedly affect post-ischemic brain temperature suggesting that the observed protection was not due to a reduction in temperature during or after the severe ischemic insult. The lack of functional protection within the first 10 days after ischemia, along with the decline of cellular preservation over time, suggests that this paradigm may not provide permanent protection.
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PMID:Ischemic preconditioning: a long term survival study using behavioural and histological endpoints. 923 27

The mRNA expression of the proinflammatory cytokine interleukin-1beta (IL-1beta) has been shown to be induced in neural elements during ischemia. It is not clear which cells generate the IL-1beta mRNA and eventually synthesize IL-1 protein and which cells respond to this signaling by producing IL-1 receptors during ischemia. To clarify this question, rats were subjected to global ischemia by bilateral carotid occlusion and hypotension for 20 minutes, followed by reperfusion for 2 hours (n = 7), 8 hours (n = 7), or 24 hours (n = 7). Cryostat sections were hybridized using antisense oligonucleotide probes (30 dimer). Multiple cell markers were used in immunohistochemical staining to identify the cells expressing IL-1beta and IL-1R protein. The sham animals (n = 5) showed no or only a weak expression of IL-1R or IL-1beta mRNA. The number of IL-1beta mRNA-expressing cells was significantly increased by 2 hours of reperfusion in several brain areas including cortex (12-fold compared with sham) and caudate-putamen (14-fold), and was maximally increased in most hippocampal regions by 8 hours of reperfusion (mean +/- SD of positive cells/field versus sham equivalent being 37.9 +/- 12.3 versus 4.0 +/- 3.3; 30.6 +/- 9.0 versus 3.1 +/- 2.3; 41.3 +/- 17.5 versus 2.9 +/- 1.9; in CA1; CA2; CA3/CA4 regions of the hippocampus, respectively). IL-1beta mRNA signal was also intensified in the white matter areas. Changes in IL-1R mRNA were seen in the hippocampus (after 2 hours CA1: 16-fold; CA2: 17-fold; DG: 24-fold increase; and CA3/CA4: 10-fold increase after 8 hours), and the expression was prolonged especially in CA1 and CA2 regions up to 24 hours of reperfusion. The major cellular source of IL-1beta protein was glia (astrocytes, oligodendrocytes, microglia, and scattered perivascular macrophages/monocytes), while neurons and sporadic microvascular endothelia showed IL-1R immunoreactivity. The data suggest that neurons in discrete areas vulnerable for selective neuronal death, and possibly the vascular endothelium, are target cells for ischemia-induced glial IL-1beta production.
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PMID:Global forebrain ischemia results in differential cellular expression of interleukin-1beta (IL-1beta) and its receptor at mRNA and protein level. 934 36

A recently identified neuronal Na+-dependent phosphate cotransporter (rBNPI) has been shown to import inorganic phosphate (P(i)) required for the production of high-energy phosphates which are vital to neuronal energy metabolism. In the present study, we have examined the expression of rBNPI mRNA in the hippocampus of rats subjected to 30 min of global ischemia by four-vessel occlusion. In situ hybridization reveals that transient forebrain ischemia results in a selective reduction in rBNPI mRNA expression in CA1 pyramidal neurons of the hippocampus. Expression of rBNPI is significantly reduced by 24 h and completely absent at 72 h following global ischemia when CA1 pyramidal neurons begin to show cell damage. By contrast, there is no change in the expression of Nedd2 mRNA, a developmentally regulated cell death gene, in CA1 pyramidal neurons at these same time points. The loss of rBNPI transcripts appears to be selective for CA1 pyramidal neurons since rBNPI mRNA expression is unchanged in neurons of the CA2-CA4 pyramidal cell layers following global ischemia. Our data indicate that an early reduction of rBNPI transcripts may contribute to a reduction in P(i)-dependent energy metabolism or signal transduction which has been reported in CA1 hippocampal neurons following global ischemia.
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PMID:Selective loss of neuronal Na+-dependent phosphate cotransporter mRNA in CA1 pyramidal neuron following global ischemia. 937 33

Both acute and chronic treatments with the glycine partial agonist 1-aminocyclopropanecarboxylic acid (ACPC) are neuroprotective in animal models of focal, global and spinal ischemia. After a chronic regimen of ACPC, brain and plasma levels were undetectable at the time of ischemic insult, which suggests that the neuroprotective effects of acute and chronic ACPC are mediated by different mechanisms. To investigate the possibility that chronic administration of ACPC alters N-methyl-D-aspartate (NMDA) receptor composition, the levels of mRNAs encoding zeta and epsilon subunits were quantified by in situ hybridization histochemistry with 35S-labeled riboprobes. Chronic ACPC administered to mice (200 mg/kg for 14 days) increased the level of epsilon-1 mRNA in the hippocampus (particularly CA1 and CA2 regions) and cerebral cortex (frontal, parietal and occipital regions), without altering levels in cerebellum. In contrast, this regimen decreased epsilon-3 subunit mRNA levels in the hippocampus (especially CA1 and dentate gyrus) and frontal and occipital cortices. Decreases in epsilon-2 subunit mRNA levels in cerebral cortex (especially frontal and parietal cortices) were also observed without accompanying alterations in the cerebellum, hippocampus or dentate gyrus. The levels of zeta subunit mRNA (determined with a probe that detects all splice variants) were not altered in any brain areas examined. Based on studies in recombinant receptors, these region-specific changes in mRNAs produced by a chronic regimen of ACPC could result in NMDA receptors with reduced affinities for glycine and glutamate. It is hypothesized that such alterations in NMDA receptor subunit composition may explain the neuroprotective effects produced by chronic ACPC.
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PMID:Chronic administration of a glycine partial agonist alters the expression of N-methyl-D-aspartate receptor subunit mRNAs. 940 27

Administration of endogenous corticosterone to intact animals induces calbindin-D28k protein in the hippocampal CA1-CA2 subfields. The fact that this effect on calbindin-D28k was shown to be specific for the hippocampus argues for a receptor-mediated effect on gene expression. In addition, chronic pretreatment with corticosterone aggravates ischemia-induced neuronal damage in the CA3-CA4 subfields. This effect is similar to that of preischemic hyperglycemia, which also induces postischemic seizures and aggravates brain damage, since corticosterone raises blood glucose level and enhances tissue lactic acidosis during ischemia. The energetically compromising qualities of corticosterone indicates that it is a key factor in hippocampal vulnerability. We assume that the increase of calbindin-D28k expression in the CA1-CA2 subfields in corticosterone-treated animals is an adaptive response to the exogenous stress. The lack of adaptive response in CA3-CA4 neurons endangers them by impairing the ability of these neurons to counteract the deleterious effects of calcium. This finding, supports: (1) the hypothesis that corticosterone treatment, when paired with an ischemic insult, causes a prolonged elevation of neuronal [Ca2+]i, in an energy dependent manner, probably through the reduction of calcium efflux and (2) that neurons which do contain calbindin-D28k are particularly predisposed to ischemic insults. The CA1-CA2 neurons express high amounts of calbindin-D28k under stress conditions because their activity may involve a high rate of calcium buffering.
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PMID:Synergy between chronic corticosterone treatment and cerebral ischemia in producing damage in noncalbindinergic neurons. 950 Sep 60


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