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

Our previous studies have shown that kynurenic acid (KYN), a broad-spectrum antagonist of excitatory amino acids (EAAs), administered in situ through a dialysis probe can delay the massive ionic fluxes in the rat hippocampus during cerebral ischemia. The present experiments demonstrated that the same procedure attenuates the increase in extracellular concentration of lactate ([lactate]e) during ischemia as measured by microdialysis. This finding suggests that the lactate accumulation is partially caused by a sudden increase in energy demand due to the rapid ionic fluxes through EAA-coupled ion channels. This inference is consistent with the hypothesis that the earlier ionic event during ischemia is a cause of energy depletion, rather than the result merely of energy failure. The present experiments also revealed that KYN administered by the same procedure attenuates death of hippocampal CA1 pyramidal cells after 5-min transient ischemia in gerbils. Since lactate accumulation is likely to be an important factor affecting cell viability, the protective effect of KYN may be attributable, in part, to inhibition of lactate accumulation.
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PMID:Excitatory amino acid antagonist administered via microdialysis attenuates lactate accumulation during cerebral ischemia and subsequent hippocampal damage. 151 51

The neuroprotective action of a cholecystokinin octapeptide analogue, ceruletide, was evaluated in models of cerebral ischemia using Mongolian gerbils. Ceruletide significantly suppressed the hyperactivity and amnesia induced by ischemia when injected s.c. 30 min before 5-min occlusion of the bilateral common carotid arteries at room temperature or immediately after their reperfusion. Ceruletide also reduced behavioral changes in ischemic gerbils whose body temperature was maintained at 37 degrees C during the 3-min occlusion. In these groups, delayed neuronal cell death in the hippocampal CA1 area following ischemia was markedly attenuated by s.c. administration of ceruletide. On the other hand, ceruletide could not inhibit the behavioral changes or the neurodegeneration induced in the hippocampal CA1 area by 5-min occlusion at 37 degrees C. These findings indicate that peripheral injection of ceruletide produces a neuroprotective action against moderate cerebral ischemia, which is the first evidence suggesting the efficacy of ceruletide in neurodegenerative diseases.
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PMID:Systemic administration of a cholecystokinin analogue, ceruletide, protects against ischemia-induced neurodegeneration in gerbils. 151 36

Ischemia for 5 min temporarily increased locomotor activity in gerbils after 1 and 3 days. Temporary increases were also noted within 7 and 5 days after 20-min ischemia and repeated ischemia (three 2-min ischemia at 1-h intervals), respectively. In a passive avoidance task, gerbils were trained 2 or 14 days before the occlusion and then tested 1 day after it. Shortened step-through latency was observed in the retention test 3 days after 5-min ischemia, but not after 15 days (reversible deficit). In contrast, following 20-min ischemia, the step-through latency was significantly lower after 3 days and also after 15 days (irreversible deficit). Working memory was also tested with gerbils trained for an 8-arm radial maze task. A significantly higher working error was observed 1 day after 5-min ischemia but not after 5 days (reversible deficit). However, ischemia for 20-min and repeated ischemia led to markedly increase working error 1 day after the occlusion, with significant increases even after 14 and 28 days (irreversible deficit). In addition, while 5-min ischemia occurred the neuronal death in the hippocampal CA1 subfield, 20-min ischemia produced it not only in the CA1 subfield but also in the CA2-4 subfield and dorsal striatum. These results indicated that 5-min ischemia led to a reversible memory deficit, while 20-min and repeated ischemia produced an irreversible deficit.
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PMID:Ischemia-induced irreversible deficit of memory function in gerbils. 152 Nov 47

Halothane anesthetized Sprague-Dawley rats underwent 10 min of bilateral carotid artery occlusion with mean arterial pressure (MAP) held at 30, 50 or 60 mmHg. Sham rats did not undergo ischemia. A 7-day recovery interval was allowed. Intra-ischemic electroencephalographic (EEG) changes, behavioral function (Days 5-7), and histologic injury (Day 7) were evaluated. Under similar conditions, cerebral blood flow was determined after 10 min ischemia by the [3H]nicotine indicator fractionation technique. EEG isoelectricity was observed in 11 of 11, 5 of 10, and 2 of 11 rats in the 30 mmHg, 50 mmHg, and 60 mmHg groups respectively. Neither passive avoidance cross-over latencies nor general motor scores were affected by intra-ischemic MAP and no differences from sham performance were observed. The per cent of CA1 neurons counted as dead (left and right hemispheres combined) was significantly affected by intra-ischemic MAP (72, 46 and 28% in the 30 mmHg, 50 mmHg, and 60 mmHg groups, respectively; P less than 0.001). A greater than 50% CA1 neuronal mortality rate was present only in those rats exhibiting EEG isoelectricity. However, the number of rats demonstrating greater than a 25% interhemispheric difference in CA1 neuronal loss was greatest in the 50 mmHg group (P less than 0.02). Hippocampal blood flow decreased in association with severity of hypotension (8 +/- 1, 35 +/- 8, and 48 +/- 2 ml/100 g/min (mean +/- S.E.M.) for 30, 50, and 60 mmHg, respectively; P less than 0.01). Again, however, the greatest variability in blood flow was observed at MAP = 50 mmHg.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of intra-ischemic blood pressure on outcome from 2-vessel occlusion forebrain ischemia in the rat. 152 Nov 52

We examined the changes in immunoreactivity of microtubuli-associated protein (MAP) 2 in dendrites by immunohistochemical analysis following 20 min of cerebral ischemia in the rat. A decrease of immunoreactivity of MAP 2 in dendrites in the CA1 subfield of the hippocampus was observed on days 3 and 7 but not on day 1 after ischemia. Early destructive changes of this protein were not observed, a finding which was confirmed by polyacrylamide gel electrophoresis analysis. We elucidated one factor which indicated that destruction of the dendrites of CA1 pyramidal neurons would not take place any earlier than the destruction of the neurons themselves after ischemia in rats.
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PMID:Absence of early destructive changes of cytoskeletal proteins after transient ischemia in the rat. 152 Nov 63

We examined the time course of basic fibroblast growth factor (bFGF) immunoreactivity and its mRNA level mainly in the hippocampus after transient forebrain ischemia using immunohistochemistry, enzyme immunoassay (EIA), Western blot analysis and in situ hybridization. Neuronal death in the hippocampal CA1 subfield was observed 72 h after 20 min of ischemia. The number of bFGF-immunoreactive(IR) cells increased 48 h-5 days after ischemia in all hippocampal regions. At 10 and 30 days, the bFGF-IR cells in the CA1 subfield had further increased in numbers and altered their morphology, enlarging and turning into typical reactive astrocytes with the advancing neuronal death in that area. In contrast, the number of bFGF-IR cells in other hippocampal regions had decreased 30 days after ischemia. The EIA study showed a drastic increase in bFGF levels in the hippocampus 48 h after ischemia (150% of that in normal rat) which was followed by further increases. In Western blot analysis, three immunoreactive bands whose molecular weights correspond to 18, 22 and 24 kDa were observed in normal rat and ischemia increased all their immunoreactivities. In the in situ hybridization study of the hippocampus, bFGF mRNA positive cells were observed in the CA1 subfield in which many bFGF-IR cells existed after ischemia. These data demonstrate that transient forebrain ischemia leads to an early and strong induction of bFGF synthesis in astrocytes, suggesting that the role of bFGF is related to the function of the reactive astrocytes which appear following brain injury.
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PMID:Increase of basic fibroblast growth factor immunoreactivity and its mRNA level in rat brain following transient forebrain ischemia. 152 98

We used monoclonal antibodies to examine the immunohistochemical distribution of the three major Ca(2+)-dependent protein kinase C (PKC) isozymes (I, II, and III) in ischemic gerbil hippocampus. Groups of four animals were sacrificed at 15 min, 4 h, 1 day, 2 days, 3 days, and 7 days after a 10-min episode of global forebrain ischemia. In control animals, PKC-I immunoreactivity was greater in CA1 neurons than in CA3-4. Terminal-like staining was not evident. PKC-II immunoreactivity was observed in all CA fields and in the outer molecular layer of the dentate gyrus. PKC-III staining was present in the CA fields, the inner molecular layer of the dentate gyrus and the subiculum. Dentate granule cells and mossy fibers were not stained with any of the PKC antibodies. Fifteen minutes and 4 h after ischemia, PCK-I, -II and -III immunoreactivity were all increased in CA1 neurons and PKC-III immunoreactivity alone was visualized in granule cells and mossy fibers. Staining patterns returned to baseline one day after ischemia. PKC-II and -III terminal-like staining were preserved in the stratum lacunosum-moleculare for 3 days and 2 days after ischemia respectively and then disappeared. The altered patterns of PKC staining in the hippocampus may reflect activation and/or down-regulation of PKC isozymes. Ca(2+)-dependent PKC isozymes may, therefore, potentially play a role in the pathogenesis of delayed ischemic neuronal death.
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PMID:Immunohistochemical distribution of protein kinase C isozymes is differentially altered in ischemic gerbil hippocampus. 152 42

We attempted to determine if the cholinomimetic activity of the psychotropic drug minaprine was related to the amelioration of the delayed neuronal death induced by cerebral ischemia in Mongolian gerbils. Minaprine improved the passive avoidance deficit induced by cerebral ischemia, and the histopathological ischemic neuronal changes in the hippocampal CA1 neurons were diminished. These effects were completely inhibited by treatment with the cholinergic blocker scopolamine. Rectal temperature fell about 1.5 degrees C immediately after cerebral ischemia and hyperthermia occurred 30 and 60 min after recirculation. Minaprine had no effect on body temperature before or after ischemia. Physostigmine and tetrahydroaminoacridine (THA), drugs which stimulate the cholinergic system, improved passive avoidance deficits and prevented the delayed neuronal death. These effects of physostigmine and THA were completely inhibited by scopolamine. Pentobarbital and diazepam also improved the passive avoidance deficit and prevented the destruction of CA1 neurons. In contrast with minaprine, these effects of pentobarbital and diazepam were not inhibited by scopolamine. As the protective effect of minaprine against ischemia-induced delayed neuronal death is related to cholinomimetic activities, these events differ from those seen with pentobarbital and diazepam.
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PMID:Cholinomimetic activity of minaprine is related to the amelioration of delayed neuronal death in gerbils. 152 97

We studied the alterations in the binding of muscarinic cholinergic and adenosine A1 receptors following transient cerebral ischemia in Mongolian gerbils and examined the effects of the novel vinca alkaloid derivative vinconate and pentobarbital against the alterations in the binding of these receptors. Animals were allowed to survive for 5 h and 7 days after 10 min of cerebral ischemia induced by bilateral occlusion of common carotid arteries. [3H]Quinuclidinyl benzilate (QNB) and [3H]cyclohexyladenosine (CHA) were used to label muscarinic cholinergic and adenosine A1 receptors, respectively. The [3H]QNB and [3H]CHA bindings showed no significant alteration in the gerbil brain 5 h after ischemia. However, these bindings in the striatum, the hippocampal CA1 sector, and the hippocampal CA3 sector revealed a significant reduction 7 days after ischemia. The [3H]CHA binding also showed a significant decline in the dentate molecular layer 7 days after ischemia. Intraperitoneal application of vinconate (100 and 300 mg/kg) 10 min and pentobarbital (40 mg/kg) 30 min before ischemia showed a mild reduction in the [3H]CHA binding in the brain 5 h after ischemia. Especially, the reduction was found in the hippocampal CA1 sector and the dentate molecular layer. However, the [3H]QNB binding revealed no significant alteration in the brain 5 h after ischemia. Seven days after ischemia, both drugs prevented a marked reduction in the [3H]CHA binding in the striatum, but not in the hippocampal CA1 sector, the hippocampal CA3 sector, and the dentate molecular layer. By contrast, vinconate and pentobarbital failed to prevent the reduction in the [3H]QNB binding in the striatum. Morphological study indicated that vinconate and pentobarbital ameliorated the neuronal damage to the striatum, but not the hippocampal damage 7 days after ischemia. This histological finding was relatively consistent with the alteration in the [3H]CHA binding. These receptor autoradiographic and histological data suggest that vinconate and pentobarbital can protect the brain from both cellular and functional consequences of ischemia. These findings are of interest in relation to the mechanisms of ischemic brain damage.
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PMID:Postischemic alteration of muscarinic acetylcholine and adenosine A1 binding sites in gerbil brain. Protective effects of a novel vinca alkaloid derivative, vinconate, and pentobarbital using an autoradiographic study. 152 67

Delayed neuronal death induced by transient forebrain ischemia in the rat hippocampus is preceded by a prominent microglial reaction which begins within minutes after the ischemic injury. In the present study we have examined the effect of the non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 on microglial activation and neuronal survival. Using lectin histochemistry to detect microglia, we show that the systemic administration of MK-801 prior to ischemia prevents microglial activation, as well as delayed death of CA1 pyramidal neurons. The results demonstrate that early blockage of the glutamate cascade prevents microglial activation, and could suggest a role for microglia in mediating ischemic injury.
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PMID:MK-801 prevents microglial reaction in rat hippocampus after forebrain ischemia. 153


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