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

Potassium channels that are activated by decreasing adenosine trisphosphate levels are blocked by sulfonylurea drugs such as glibenclamide but are opened by diazoxide and some endogenous peptides. Judging from the effects of such drugs, it seems that in the hippocampus, these channels are present not on cell bodies but rather on glutamate-releasing nerve terminals (especially those of mossy fibers in the CA3 region). Because activation of these presynaptic potassium channels reduces anoxic glutamate release, they may be a useful target for specific drug therapy that might prevent the excitoxic effects of excessive glutamate release during anoxia/ischemia.
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PMID:Adenosine triphosphate-sensitive potassium channels in anoxia. 212 55

Transient ischemia in normoglycemic animals leads to delayed neuronal damage which is confined to selectively vulnerable regions. In at least one of these, the CA1 sector of the hippocampus, cell death is preceded by neuronal hyperactivity, presumed to be caused by loss of inhibitory control. Hyperglycemic subjects develop postischemic seizures, and show enhanced damage. The ATP-sensitive K+ channel, which may be important in inhibitory control, is the target of antidiabetic sulfonylureas. We determined densities of sulfonylurea binding sites in rat brain after forebrain ischemia. Normoglycemic animals showed a decrease of glibenclamide receptor binding in the CA3 field, hilus and dentate gyrus of the hippocampus after 1 day of recovery. After 4 days of recovery, levels of sulfonylurea binding sites decreased mainly in the CA1 field and in the hilus, as well as in the substantia nigra. After 1 day of recovery, hyperglycemic animals did not show any significant variations of densities of sites compared to control animals. It is proposed that reduction of inhibitory control by ATP-sensitive K+ channels may be associated with delayed neuronal death.
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PMID:Brain ischemia alters the density of binding sites for glibenclamide, a specific blocker of ATP-sensitive K+ channels. 212 31

The protective roles of Ca2+ channel blockers against ischemic hippocampal damage are still debated. We used autoradiography to study postischemic L-type Ca2+ channels (1,4-dihydropyridine Ca2+ channel blocker binding), adenosine A1 receptors, and muscarinic cholinergic receptors in the rat hippocampus using [3H]PN200-110 (PN), [3H]cyclohexyladenosine (CHA), and [3H]quinuclidinyl benzilate (QNB), respectively, in 49 rats subjected to 20 minutes of forebrain ischemia. The rats were decapitated after 1 (n = 7), 3 (n = 7), 6 (n = 8), 12 (n = 7), 24 (n = 6), 48 (n = 6), or 168 (n = 8) hours of recirculation; eight control rats were sham-operated but experienced no cerebral ischemia. Reduced receptor binding preceding the delayed death of CA1 pyramidal cells was first observed in the stratum oriens of the CA1 subfield. Significant reductions in [3H]PN, [3H]CHA, and [3H]QNB bindings of this stratum compared with control were noticed after 3 (35%, p less than 0.01), 12 (31%, p less than 0.01), and 1 (10%, p less than 0.05) hours of recirculation, respectively. By 168 hours after ischemia (when the populations of CA1 pyramidal cells were depleted) all strata in the CA1 subfield had lost most of their receptor sites, and [3H]PN, [3H]CHA, and [3H]QNB bindings in the stratum oriens were decreased to 23%, 30%, and 63% of control (p less than 0.01). Although [3H]PN binding in the CA3 subfield did not change significantly during 168 hours after ischemia, the histologically intact dentate gyrus exhibited a 31% loss of binding sites compared with control (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Calcium antagonist, adenosine A1, and muscarinic bindings in rat hippocampus after transient ischemia. 214 Feb 13

Cerebral ischemia produces a disruption of calcium homeostasis in neurons. This may explain the extreme sensitivity of these cells to ischemic insult. Prolonged increases in calcium levels may produce irreversible damage to the cell by altering important calcium-dependent enzyme systems such as calcium/calmodulin-dependent protein kinase II. Five minutes of acute forebrain ischemia in the gerbil produced a significant decrease in calcium/calmodulin-dependent protein kinase II activity as early as 10 seconds postischemia and persisting up to 7 days after insult. Because hypothermia protects against ischemia-induced cell death in the gerbil, we examined the effect of ischemia on cell death and calcium/calmodulin-dependent protein kinase II at different intracerebral temperatures: hyperthermia (39 degrees C), normothermia (36 degrees C), and hypothermia (32 degrees C). In ischemic animals, hyperthermia produced severe loss of neurons in CA1 and moderate loss in CA3-CA4 subregions. Normothermia in ischemic animals produced severe loss of neurons in the CA1 subregion. Hypothermic ischemic animals showed no significant loss of neurons in any hippocampal region. Ischemia produced a severe decrease (17 +/- 6% of control) in calcium/calmodulin-dependent kinase II activity in hyperthermic animals, a moderate decrease (55 +/- 15% of control) in normothermic animals, and no decrease of enzyme activity in hypothermic animals. Thus, lowering and raising intracerebral temperature decreased and increased, respectively, the extent of ischemia-induced damage in the gerbil. Because ischemia-induced effects on calcium/calmodulin-dependent protein kinase II activity are rapid and long-lasting, hypothermia may protect through preservation of calcium/calmodulin-dependent protein kinase II activity.
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PMID:Effects of ischemia on multifunctional calcium/calmodulin-dependent protein kinase type II in the gerbil. 217 73

The immunocytochemical distribution of manganese superoxide dismutase (Mn-SOD) was determined in the rat hippocampus. The enzyme was localized in the mitochondria. CA1 pyramidal cells were weakly immunostained, whereas CA3 pyramidal cells were strongly reactive. These differences in the intensity of the Mn-SOD immunostaining reactions may relate to variations in the sensitivity of subfields of the hippocampus to ischemia.
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PMID:Immunocytochemical localization of manganese superoxide dismutase (Mn-SOD) in the hippocampus of the rat. 221 54

We examined mRNA, cytoplasmic RNA and structural damage in the hippocampus of the gerbil brain after transient ischemia by in situ hybridization, Acridine orange histochemistry and immunohistochemistry. Progressive decline of mRNA became visible in the CA1 region after reperfusion for 3 h and loss of cytoplasmic RNA and emergence of structural damage in 3 days. Reduction of mRNA in the CA3-CA4 region was transient. The findings suggested positive correlation between progressive loss of mRNA and delayed neuronal death.
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PMID:Progressive loss of messenger RNA and delayed neuronal death following transient cerebral ischemia in gerbils. 223 95

We correlated the efficacy of several clinically relevant pharmacotherapies with their ability to prevent calcium influx into neurons and subsequent binding to calmodulin. We studied the administration of CGS 19755, nimodipine, nicardipine, and combinations of these drugs before or immediately after ischemia in globally ischemic rats. Calcium-calmodulin binding was graded by an immunohistochemical assay after 2 and 24 hours of reperfusion (n = 5-6 at each time period), and histologic damage was graded by light microscopy after 72 hours of reperfusion (n = 6). Calcium-calmodulin binding correlated with the severity of delayed histologic damage in various brain regions. In untreated ischemic control rats, marked calcium-calmodulin binding was seen in CA1 and CA3 after 24 hours of reperfusion (p less than or equal to 0.01). Administered before ischemia, CGS 19755 prevented calcium-calmodulin binding across all brain regions after 2 and 24 hours of reperfusion compared with controls (p less than or equal to 0.05). This effect was most prominent in CA3 and CA1, where the drug also reduced delayed neuronal damage (p less than or equal to 0.05). Lower doses or postischemic administration of CGS 19755, nimodipine, nicardipine, and a combination of postischemic CGS 19755 and nicardipine had a more limited effect on calcium-calmodulin binding and did not protect against delayed neuronal damage.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Neuronal protection correlates with prevention of calcium-calmodulin binding in rats. 223 82

We investigated the effect of a novel quinazoline derivative (KB-5666), a lipid peroxidation inhibitor, on ischemic neuronal damage using Mongolian gerbils. The animals were sacrificed 7 or 30 days after 5 min of forebrain ischemia induced by bilateral common carotid artery occlusion. Morphologic changes, a microtubule-associated protein 2 (MAP2) immunohistochemical study and quantitative autoradiographic study using [3H]phorbol 12, 13-dibutyrate ([3H]PDBu) were evaluated in the hippocampus after ischemia. KB-5666 (3-50 mg/kg, i.v.) showed protective effects against neuronal death of the CA1 subfield 5 min before ischemia, immediately or 1 hr after ischemia, but not 4 hr after ischemia. KB-5666 (i.p.) also showed protective effects in a dose-dependent manner immediately after ischemia. Furthermore, KB-5666 dose-dependently prevented a marked decrease in microtubule-associated protein 2 immunoreactivity in the dendritic fields of the CA1 pyramidal cells after ischemia. The [3H]PDBu binding activity in the stratum oriens and the stratum lacunosum-moleculare of the CA1 subfield was reduced by 19 and 30%, respectively, 7 days after ischemia. [3H]PDBu binding sites were unchanged in the stratum oriens in the CA3 subfield. By contrast, in the molecular layer of the dentate gyrus, the [3H]PDBu binding activity increased by 15%. KB-5666 (i.v.) prevented a decrease in the [3H]PDBu binding activity in the stratum oriens and stratum lacunosum-moleculare of the CA1 subfield and an increase in the molecular layer of the dentate gyrus. These histologic, immunohistochemical and receptor-autoradiographic data indicate that KB-5666 protects the brain from both cellular and functional consequences of ischemia.
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PMID:Prevention of hippocampus neuronal damage in ischemic gerbils by a novel lipid peroxidation inhibitor (quinazoline derivative). 224 57

We investigated the distribution of neuronal damage following brief cerebral transient ischemia and repeated ischemia at 1-h intervals in the gerbil, using light microscopy and 45Ca autoradiography as a marker for detection of ischemic damage. The animals were allowed to survive for 7 days after ischemia induced by bilateral carotid artery occlusion. Following 2-min ischemia, neuronal damage determined by abnormal calcium accumulation was not observed in the forebrain regions. Following 3-min ischemia, however, abnormal calcium accumulation was recognized only in the hippocampal CA1 sector and part of the striatum. Two 2-min ischemic insults caused extensive abnormal calcium accumulation in the dorsolateral part of striatum, the hippocampal CA1 sector, the thalamus, the substantia nigra and the inferior colliculus. The ischemic insults were more severe than that of a single 3-min ischemia. However, three 1-min ischemic insults caused abnormal calcium accumulation only in the striatum. On the other hand, three 2-min ischemic insults caused severe abnormal calcium accumulation in the brain. The abnormal calcium accumulation was found in the dorsolateral part of striatum, the hippocampal CA1 sector, the thalamus, the medial geniculate body, the substantia nigra and the inferior colliculus. Gerbils subjected to three 3-min ischemic insults revealed most severe abnormal calcium accumulation. Marked calcium accumulation was seen not only in the above sites, but also spread in the neocortex, the septum and the hippocampal CA3 sector. Morphological study after transient or repeated ischemia indicated that the distribution and frequency of the neuronal damage was found in the sites corresponding to most of the regions of abnormal calcium accumulation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Neuronal damage and calcium accumulation following repeated brief cerebral ischemia in the gerbil. 224 27

We used brief bilateral carotid artery occlusion in gerbils to examine the effects of temperature on ischemia-induced inhibition of calcium/calmodulin-dependent protein kinase II activity and neuronal death. In normothermic (36 degrees C) gerbils, ischemia induced a severe loss of hippocampal CA1 pyramidal neurons measured 7 days after ischemia (28.4 neurons/mm, n = 10; control density in 10 naive gerbils 262.1 neurons/mm) and a significant decrease in forebrain calcium/calmodulin-dependent protein kinase II autophosphorylation measured 2 hours after ischemia (12.9 fmol/min, n = 6; control phosphorylation in six naive gerbils 23.5 fmol/min). The effect of temperature on these indicators of ischemic damage was examined by adjusting intracerebral temperature before and during the ischemic insult. Hyperthermic (39 degrees C) gerbils showed almost complete loss of neurons in the CA1 region (3.0 neurons/mm, n = 11) and extension of neuronal death into the CA2, CA3, and CA4 regions. In addition, hyperthermia exacerbated ischemia-induced inhibition of calcium/calmodulin-dependent protein kinase II activity (4.2 fmol/min, n = 6). Hypothermia (32 degrees C) protected against ischemia-induced CA1 pyramidal cell damage (257.0 neurons/mm, n = 20) and inhibition of calcium/calmodulin-dependent protein kinase II activity (26.0 fmol/min, n = 6). Our results are consistent with the hypothesis that loss of calcium/calmodulin-dependent protein kinase II activity may be a critical event in the development of ischemia-induced cell death.
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PMID:Temperature modulation of ischemic neuronal death and inhibition of calcium/calmodulin-dependent protein kinase II in gerbils. 226 78


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