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

Hypoxia-ischemia induced by unilateral carotid ligation followed by either 15 (moderate) or 90 (severe) min exposure to 8% oxygen was associated with induction of IGF-BP 2 mRNA expression. A specific rat IGF-BP 2 cDNA probe was used to determine the IGF-BP 2 mRNA distribution in brain sections using in situ hybridization. Untreated control rats and the non-ligated hemisphere in experimental rats expressed IGF-BP 2 mRNA in the choroid plexus, meninges and more weakly in the thalamus, hippocampus and cortical layer 5. Increased expression in experimental rats was limited to regions known to have neuronal damage. Three days after the moderate insult the signal was increased in the CA1/2 region of the hippocampus and thalamus of the ligated side. Three days after the severe insult IGF-BP 2 expression was found surrounding the infarcted regions while by 5 days after severe insult the whole infarcted volume showed induction. The results suggest a role for the IGFs in the post-asphyxial response. IGF-BP 2 may alter the bio-availability of IGF 1 or 2 or modulate their actions in the area of infarction, and thus promote cerebral repair and recovery.
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PMID:Expression of insulin-like growth factor-binding protein 2 (IGF-BP 2) following transient hypoxia-ischemia in the infant rat brain. 127 50

The topical and temporal relationship between neuronal injury and calcium loading was investigated in gerbils following bilateral carotid artery occlusion for 5 or 10 min and recirculation times from 15 min to 7 days. The association of histochemically visible calcium deposits with neuronal death was assessed by combining two calcium stains, alizarin red and arsenazo III, with conventional histological techniques. Neuronal calcium accumulation was evaluated morphometrically in the striatum, the frontoparietal cortex and the CA1 and CA4 sectors of the hippocampus. After 5-min ischemia and 1-2 days of recirculation numerous calcium-containing neurons appeared in the CA4 sector but only a few were present in the CA1 sector. After 4 days of recirculation calcium accumulation was visible in the whole CA1 sector and the dorso-lateral part of striate nucleus. After 10-min ischemia calcium accumulation started in these regions, as well as in the cortex, already after 1 day. In the CA1 sector calcium accumulation followed a typical time course: on day 2 only the lateral parts were affected, while on day 4 the whole CA1 neuronal band was calcium positive. The regional distribution of histological lesions matched that of calcium loading and, furthermore, the lesions appeared after a corresponding delay in the respective regions. Morphometric evaluations of calcium staining and histological lesions in the CA1 sector revealed a high correlation, indicating that calcium accumulation and neuronal death are closely associated both topically and temporally. This suggests that disturbances of calcium homeostasis such as those measured by this histochemical technique are the consequence of and not the reason for ischemic cell death.
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PMID:Time profile of calcium accumulation in hippocampus, striatum and frontoparietal cortex after transient forebrain ischemia in the gerbil. 127 27

Ischemic insult induces neuronal death in the CA1 subfields of the hippocampus which are designated generally as the most vulnerable brain region. Recent studies have shown that acidic and basic fibroblast growth factors are potent trophic factors that support the survival of neurons in many brain regions including the hippocampus. Here we demonstrate that continuous infusion of acidic fibroblast growth factor into the lateral cerebral ventricles beginning 2 days before ischemia prevents the death of the CA1 pyramidal cells in the hippocampus of gerbils. Furthermore, delayed continuous administration of acidic fibroblast growth factor starting 5 min after ischemia is equally protective. The results suggest a possible physiological function for acidic fibroblast growth factor in the normal support of hippocampal CA1 pyramidal cells and neurons in some other brain regions in considering the broad spectrum of responsive neurons.
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PMID:Acidic fibroblast growth factor prevents death of hippocampal CA1 pyramidal cells following ischemia. 128 24

The acidic fibroblast growth factor (aFGF) in rat cerebrospinal fluid (CSF) increased 1000 times in the 2 hr period after food intake, or intraperitoneal (IP) or intracerebroventricular (ICV) glucose infusion. It diffused into the brain parenchyma and was taken up into neurons in the hypothalamus, hippocampus, etc.... aFGF is produced in the ependymal cells and released into CSF in response to increased glucose. ICV application of aFGF dose dependently inhibits, and anti-aFGF antibody facilitates food intake. IP injection of glucose 2 hr before a task that combined acquisition with passive avoidance significantly increased retention of avoidance by mice tested 24 hr later. In a Morris water maze task, IP glucose injection 2 hr before a first trial block reduced time to find and climb onto a platform hidden just below the water surface. These facilitation by glucose of affective and spatial memory were abolished by pretreatment with anti-aFGF antibody applied ICV. Continuous ICV infusion of aFGF into rats also significantly increased the reliability of passive avoidance for several days. The memory facilitation by aFGF was significantly attenuated by CA1 neuron death in the hippocampus caused by 5 min ischemia of the brain, in gerbils. After food intake, centrally-released aFGF reaches the hippocampus and facilitates memory, while peripherally released cholecystokinin reaches the endings of the afferent vagal nerves in the portal vein and changes the vagal nerve activity, which modulates hippocampal activity, to lead to memory facilitation. This, however, is blocked by vagotomy below the diaphragm.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pathophysiological significance of brain acidic fibroblast growth factor. 128 50

It has not been discussed whether transient forebrain ischemia of 5-min duration, which is a model frequently used to evaluate pharmacological protection against ischemic injury, is an optimal model in the CA1 field of this animal whose brain temperature is maintained at normothermic levels. The temperature of the brain during an ischemic insult strongly affects the extent of the resulting neuronal injury. If the brain temperature is not regulated, it usually falls in the gerbil by 2 degrees-4 degrees C during 5-min ischemia. However, the brain temperature during ischemic insult was not regulated in many previous studies. In the present study, the effects of transient (1 to 5 min) forebrain ischemia on the development of neuronal degeneration in hippocampal regions of the gerbil whose brain temperature was maintained at 37 degrees C were examined. In the CA1 field of the hippocampus, transient ischemia of 3- and 4-min duration caused almost the same maximal damage (88%-91% neuronal loss) as observed in the gerbils subjected to 5-min ischemia. Transient ischemia of 2- and 2.5-min duration provoked substantial neuronal damage in 25% and 55% of experimental gerbils, respectively. These results indicate that 5-min bilateral forebrain ischemia is more than is necessary to examine ischemia-induced neuronal degeneration in hippocampal CA1 field of the gerbil whose brain temperature is maintained at normothermic levels. In the normothermic gerbil brain, an ischemic period of 3-min already induces extensive neuronal death in the CA1 and, thus, constitutes a sensitive model to evaluate faint protective effects of drugs against ischemic injury in the normothermic gerbil.
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PMID:Re-evaluation of ischemia-induced neuronal damage in hippocampal regions in the normothermic gerbil. 128 91

Thresholds of induction of heat shock protein (HSP) 70 and heat shock cognate protein (HSC) 70 mRNAs after transient global ischemia in gerbil brain were investigated by in situ hybridization using cloned cDNA probes selective for each mRNA species. In sham control brain, HSP70 mRNA was little present, while HSC70 mRNA was present in most cell populations. A 0.5-min occlusion of bilateral common carotid arteries did not affect the amount of HSP70 and HSC70 mRNAs. The selective induction of HSC70 mRNA was observed in dentate granule cells at 1 h, and in most cells of hippocampus especially dentate gyrus at 3 h after 1 min of ischemia when induction of HSP70 mRNA was not evident in the identical brain. The selective induction diminished by 2 days. However, after 2 min of ischemia, HSP70 and HSC70 mRNAs were induced together in hippocampal cells from 1 h of the reperfusion, and the co-induction prolonged in CA1 cells until 2 days. Body temperatures monitored at rectum increased after the reperfusion with a peak at 30 min. The degree of increase of the body temperature was significantly higher in the case after 2-min ischemia than in the cases after 0.5- and 1-min ischemia. Although HSP70 and HSC70 mRNAs are generally co-induced in stressful conditions, our results suggest the different thresholds of the induction between HSP70 and HSC70 mRNAs after transient brain ischemia. The selective induction of HSC70 mRNA which is not accompanied by the induction of HSP70 mRNA may relate to the differences of the duration of ischemia and the degree of the increase of body temperature after ischemia.
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PMID:Different thresholds of HSP70 and HSC70 heat shock mRNA induction in post-ischemic gerbil brain. 129 Oct 30

Intracellular pH can be measured quantitatively in rat brain in vivo and in vitro using spectrophotometric detection of the vital dye neutral red. This method preserves spatial information and is compatible with microhistochemistry. The intracellular pH indicated by this method is in close agreement with that indicated by 31P-NMR spectroscopy. During ischemia, intracellular acidification is correlated with tissue lactate accumulation. The spatial distribution of pH values becomes more heterogeneous as the tissue becomes more acidic. Resuscitation from total cerebral ischemia produced by cardiac arrest results in rapid intracellular realkalinization. This realkalinization is at least partially inhibited by amiloride pretreatment. Some neuronal populations, especially in the hippocampal CA1 and CA4 regions, may become more acidic during ischemia and realkalinize more slowly after reperfusion than other tissue regions. The intracellular pH of hippocampal brain slice preparations is more alkaline than expected from in vivo studies. The intracellular pH of the brain slice can be acidified to near neutrality by specific inhibitors of the sodium/hydrogen ion exchanger.
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PMID:Intracellular pH in rat brain in vivo and in brain slices. 129 77

The role of inhibitory neurotransmission in selective neuronal degeneration after transient forebrain ischemia was studied by binding of t-[35S]butylbicyclophosphorothionate ([35S]TBPS) to the gamma-aminobutyric acid (GABA)-gated chloride channel and measurement of GABAA receptor function in Mongolian gerbil brain. [35S]TBPS binding to the hippocampus, striatum, and cortex quantified by autoradiography and muscimol-stimulated 36Cl- uptake in synaptoneurosomes of the same regions were examined 1, 4, and 29 days after a 5-min bilateral carotid occlusion. [35S]TBPS binding was decreased in the pyramidal cell dendritic layers, stratum oriens, and stratum lacunosum-moleculare of the CA1 hippocampus, 4 and 29 days after occlusion, and in the stratum radiatum 29 days after occlusion. [35S]TBPS binding sites in the lateral striatum decreased 47% 4 days after occlusion. At the same time, there was a corresponding decrease in muscimol-stimulated 36Cl- uptake in the striatal synaptoneurosomes. Muscimol-stimulated 36Cl- uptake in the hippocampus decreased slightly 4 days after occlusion and more so after 29 days, although these decreases were not significant. No changes were observed in somatosensory cortex at any time point. These data suggest that a portion of GABAA receptors in areas sensitive to ischemic insult are associated with degenerating neurons, whereas other GABAA) receptors are spared.
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PMID:Alterations in the gamma-aminobutyric acid-gated chloride channel following transient forebrain ischemia in the gerbil. 130 65

Postischemic alteration of second messenger systems was investigated in the Mongolian gerbil, utilizing [3H]phorbol 12,13-dibutyrate and [3H]inositol 1,4,5-trisphosphate receptor autoradiography. Transient ischemia was induced for 10 min, and animals were allowed to survive for various recirculation periods of up to one month. [3H]Phorbol 12,13-dibutyrate binding in selectively vulnerable areas showed no significant change 1-24 h after ischemia except for a transient decline in a few regions. Thereafter, the binding in most of the selectively vulnerable areas showed significant alteration 48 h or seven days after ischemia. Interestingly, dentate molecular layer which was resistant to ischemia showed a significant elevation in the number of [3H]phorbol 12,13-dibutyrate binding sites. One month after ischemia, [3H]phorbol 12,13-dibutyrate binding showed significant reduction only in the striatum and the hippocampal CA1 sector where severe neuronal damage was seen morphologically. A significant elevation in the number of [3H]phorbol 12,13-dibutyrate binding sites was still seen in the dentate molecular layer one month after ischemia. In contrast, [3H]inositol 1,4,5-trisphosphate binding showed significant reduction in the selectively vulnerable regions 1-24 h after ischemia. Thereafter, [3H]inositol 1,4,5-trisphosphate binding in most of the selectively vulnerable areas markedly decreased up to one month after ischemia. In the dentate molecular layer, [3H]inositol 1,4,5-trisphosphate binding also showed significant reduction during recirculation except for a slight recovery 48 h and seven days after ischemia. One month after ischemia, the binding in all regions showed significant reduction. These results suggest that postischemic alteration of two second messenger (protein kinase C and inositol 1,4,5-trisphosphate) binding sites was produced with different processes in selectively vulnerable areas.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Postischemic binding of [3H]phorbol 12,13-dibutyrate and [3H]inositol 1,4,5-trisphosphate in the gerbil brain: an autoradiographic study. 131 18

We have investigated regional and temporal alterations in Ca2+/calmodulin-dependent protein kinase II (CaM kinase II) and calcineurin (Ca2+/calmodulin-dependent protein phosphatase) after transient forebrain ischemia. Immunoreactivity and enzyme activity of CaM kinase II decreased in regions CA1 and CA3, and in the dentate gyrus, of the hippocampus early (6-12 h) after ischemia, but the decrease in immunoreactivity gradually recovered over time, except in the CA1 region. Furthermore, the increase in Ca2+/calmodulin-independent activity was detected up to 3 days after ischemia in all regions tested, suggesting that the concentration of intracellular Ca2+ increased. In contrast to CaM kinase II, as immunohistochemistry and regional immunoblot analysis revealed, calcineurin was preserved in the CA1 region until 1.5 days and then lost with the increase in morphological degeneration of neurons. Immunoblot analysis confirmed the findings of the immunohistochemistry. These results suggest that there is a difference between CaM kinase II and calcineurin in regional and temporal loss after ischemia and that imbalance of Ca2+/calmodulin-dependent protein phosphorylation-dephosphorylation may occur.
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PMID:Regional and temporal alterations in Ca2+/calmodulin-dependent protein kinase II and calcineurin in the hippocampus of rat brain after transient forebrain ischemia. 131 54


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