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Query: UMLS:C0020672 (hypothermia)
 17,327 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

We examined whether mild brain hypothermia during pretreatment with sublethal 2-min ischemia affected the tolerance to subsequent lethal 5-min ischemia. The neuronal densities in the hippocampal CA1 sector of gerbils preconditioned at mild brain hypothermia (32% of normal) were significantly lower than those in gerbils preconditioned at brain normothermia (70% of normal). 72-kDa heat-shock protein immunoreactivity in the CA1 sector preconditioned at mild hypothermia was reduced. These results suggests that mild brain hypothermia during pretreatment with sublethal ischemia reduces the tolerance to subsequent lethal ischemia.
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PMID:Intraischemic hypothermia during pretreatment with sublethal ischemia reduces the induction of ischemic tolerance in the gerbil hippocampus. 903 10

The expression of junD was studied in the rat hippocampus by in situ hybridization after 15 min of normothermic (37 degrees C) and hypothermic (33 degrees C) transient forebrain ischemia. Ischemia was induced by common carotid artery occlusion combined with hypotension leading to damage in the CA1 region of the hippocampus which was prevented by hypothermia. junD mRNA was induced in the hippocampus within 2 h of reperfusion and was strong in the dentate gyrus but weak in the CA3 and CA1 subregions. Intraischemic hypothermia significantly augmented the junD induction in the dentate gyrus. During late reperfusion (between 12 and 36 h after ischemia) a transient increase in junD mRNA was seen in the normothermic CA3 which was abolished in the hypothermic brains. In contrast, in the normothermic CA1 a continuous increase of junD was seen. This was significantly reduced by intraischemic hypothermia. We suggest that the early induction in junD expression in the dentate gyrus and in the hypothermic CA3 region is a protective reaction to the ischemic stress. The marked increase in resistant brain areas could be due to the preserved intracellular signaling pathways and a subsequent maintenance of protein synthesis. The late continuous increase, unique to the vulnerable normothermic CA1 region, suggests that junD participates in a transcriptional process that may be important for delayed neuronal death in the hippocampus following transient forebrain ischemia.
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PMID:Induction of junD mRNA after transient forebrain ischemia in the rat. Effect of hypothermia. 903 18

Many glutamate antagonists have been reported to have a neuroprotective effect against ischemic brain damage; however, some of them have been also reported to induce hypothermia that confers remarkable neuroprotection against the damage. In order to avoid the confounding effects of hypothermia, we assembled a telemeter-based brain temperature control system that allows continuous monitoring and regulating of brain temperature during an ischemic insult and in the post-ischemic period in conscious and freely moving animals. Experiments were performed in gerbils that were subjected to administration of MK-801 (3, 5, and 10 mg/kg) and/or to 5-min ischemia. The system monitored continuous changes in brain temperature and regulated brain temperature at normothermic levels, revealing that a neuroprotective effect of 3 mg/kg MK-801 against ischemia-induced delayed hippocampal CA1 neuronal death was mainly due to hypothermia, whereas a high dose of MK-801 (5 and 10 mg/kg) produced a neuroprotective effect even when the brain temperature was maintained at normothermic levels. These results indicate that this system is very useful to test potential antiischemic agents, especially when the agents have hypothermic side effects.
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PMID:Continuous monitoring and regulating of brain temperature in the conscious and freely moving ischemic gerbil: effect of MK-801 on delayed neuronal death in hippocampal CA1. 905 37

Increased intracellular calcium and cytoskeletal damage play a crucial role in neuronal death following injury such as cerebral ischemia. The effect of brain temperature on early intracellular calcium increase and neuronal cytoskeletal damage following cerebral ischemia has not been rigorously investigated. In the current communication we evaluated calmodulin (CaM) and microtubule-associated protein 2 (MAP2) in the same brain section using a double labeling immunohistochemical technique, and obtained evidence that the brain temperature has a significant effect on the early calcium increase and cytoskeletal damage as well as the delayed neuronal death occurring in CA1 sector of the gerbil hippocampus after transient forebrain ischemia. In the normothermia (36.7 degrees C) group, CaM and MAP2 immunoreactivity were markedly decreased within 48 h after ischemia and thereafter dramatic neuronal death (grade 3) was seen in the CA1 sector at 7 days. Mild hypothermia (33.3 degrees C) significantly protected against all these changes, whereas cytoskeletal damage and delayed neuronal death were aggravated by mild hyperthermia (39.7 degrees C). We conclude that mild hypothermia protects the brain against transient forebrain ischemia by reducing early cytoskeletal damage and subsequent neuronal death.
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PMID:Effects of brain temperature on calmodulin and microtubule-associated protein 2 immunoreactivity in the gerbil hippocampus following transient forebrain ischemia. 906 42

This study investigated the effect of intra-ischemic hypothermia on astroglial reactions in the hippocampus following cerebral ischemia. Mongolian gerbils were subjected to forebrain ischemia by bilateral carotid occlusion of 10 min at a) 30 degrees C and b) 37 degrees C followed by normothermic reperfusion ranging from 1 to 3 days (d). The astrocytes were visualized by immunostaining against glial fibrillary acidic protein (GFAP), and neuronal injury was evaluated by using hematoxylin-eosin staining. In normothermic brains, reactive astrocytosis was noted in 1 and 2 d postischemic animals, becoming prominent in the 3 d postischemic group. Intense GFAP-positive cells with thickened processes were noted in all regions of the hippocampus, especially the CA1 region. These cells were seen to have migrated toward the stratum pyramidale which was normally devoid of such staining. Hypothermia significantly inhibited the GFAP-upregulation seen 3 d after normothermic ischemia. There was no significant neuronal damage in the 3 d hypothermic ischemic group. Since glial cell activation, as evidenced by GFAP-upregulation, precedes as well as accompanies neuronal damage, and since hypothermia, known to be neuroprotective, inhibits glial cell activation in the 3 d postischemic brain, it appears that glial cells play critical roles in neuronal survival or death following ischemia.
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PMID:GFAP-immunoreactivity following hypothermic forebrain ischemia. 910 35

The changes in the extracellular concentration of hydrogen peroxide (H2O2) in gerbil hippocampus during ischemia and reperfusion were investigated by microdialysis coupled with fluorometry of dichlorofluorescin oxidation. In a normothermic condition (37.5 degrees C), a transient forebrain ischemia for 5 or 10 min produced a significant increase in hippocampal H2O2 immediately after the start of ischemia. The duration of this elevation after reperfusion was significantly shorter in gerbils subjected to 5 min of ischemia than in those subjected to 10 min of ischemia. Hypothermia at both 34 degrees C and 30 degrees C inhibited the increase in the H2O2 concentration during ischemia and reperfusion in gerbils subjected to 5 min of ischemia. In gerbils subjected to 10 min of ischemia, hypothermia delayed the onset of the increase in the H2O2 concentration and shortened the duration of the elevated H2O2 concentration. Hypothermia improved the histological outcome in the hippocampal CA1 neurons 7 days after ischemia. These findings suggest that the suppression of H2O2 production in ischemia and reperfusion is a possible mechanism of brain protection by hypothermia.
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PMID:The effect of hypothermia on H2O2 production during ischemia and reperfusion: a microdialysis study in the gerbil hippocampus. 911 36

Intra-ischemic hypothermia is known to protect neurons against ischemic injury. Microglial cells have been shown to become activated following ischemia and are speculated to play significant roles in the evolution of ischemic neuronal injury. In this study, we examined the effect of intra-ischemic hypothermia on the microglial reaction in the hippocampus following transient forebrain ischemia produced in gerbils by 10 min bilateral carotid occlusion at 30 degrees C or at 37 degrees C, followed by normothermic reperfusion for 1-7 days. Microglial cells were visualized by histochemical staining with isolectin-B4 from Griffonia simplicifolia. Brains subjected to normothermic ischemia showed activation of microglia at 1 day post-ischemia; this increased with further recirculation, becoming intense by 3 days and diminished by 7 days. Ischemia under hypothermic conditions was not associated with activation of microglia, and these brains showed no significant neuronal damage, whereas the brains subjected to normothermic ischemia showed extensive neuronal necrosis in the CA1 region after 1 and 7 days reperfusion. The presence of activated microglial cells in the CA1 region prior to and in parallel with evolution of ischemic neuronal damage, the lack of such activation in brains subjected to the neuroprotective action of intra-ischemic hypothermia, together with the known potential capability of microglial cells to release cytotoxic substances appear to indicate that these cells could contribute significantly to ischemic neuronal necrosis.
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PMID:Effect of hypothermia on microglial reaction in ischemic brain. 914 Oct 70

Gel retardation electrophoresis revealed that binding of a radiolabelled double-stranded oligonucleotide probe for the nuclear transcription factor activator protein-1 was markedly potentiated in the CA1 and CA3 subfields and the dentate gyrus of the hippocampus of the gerbils with transient forebrain ischemia for 5 min, which is known to induce delayed death of pyramidal neurons exclusively in the CA1 subfield. The potentiation was transient in the vulnerable CA1 subfield, but persistent up to 18 h in the resistant CA3 subfield and dentate gyrus. However, no significant alteration was detected in endogenous levels of cyclic AMP response element binding protein phosphorylated at serine133 in these three different hippocampal structures 3 h after the reperfusion. On the other hand, hypothermia during ischemia which is known to protect the CA1 subfield against ischemic damages, led to a prolonged elevation of the activator protein-1 binding up to 9 h after the reperfusion in this vulnerable subfield at least in part through expression of c-Fos protein. Moreover, activator protein-1 binding was significantly elevated in the CA1 subfield up to 12 h after forebrain ischemia for 2 min which is shown not to induce marked damages to the vulnerable subfield. These results suggest that prolonged elevation of DNA binding activity of activator protein-1 may be responsible for molecular mechanisms underlying the unique vulnerability and/or resistance of particular subfields to a transient ischemic insult in the gerbil hippocampus.
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PMID:Positive correlation between prolonged potentiation of binding of double-stranded oligonucleotide probe for the transcription factor AP1 and resistance to transient forebrain ischemia in gerbil hippocampus. 921 65

PNU-101017 is a novel, imidazoquinoline amide and benzodiazepine receptor partial agonist that has high affinity for the GABAA receptor subtypes containing the alpha 1 and alpha 3 or alpha 5 subunits. At each of these receptors, the compound is a partial agonist with approximately 50% of the intrinsic activity of the full agonist diazepam. In view of the previously demonstrated anti-ischemic effects of some GABA agonists, the purpose of this study was to determine the ability of PNU-101017 to salvage selectively vulnerable neuronal populations in the gerbil forebrain ischemia model. In an initial set of experiments, male gerbils were pretreated 30 minutes before ischemia induction (5 minutes) with PNU-101017 (3, 10, or 30 mg/kg intraperitoneally) and again 2 hours after reperfusion. In vehicle (0.05 N HC1)-treated gerbils, the loss of hippocampal CA1 neurons at 5 days was 80%. PNU-101017 was shown to produce a dose-related increase in CA1 neuronal survival; at either 10 or 30 mg/kg, the loss of CA1 neurons was only 21% (P < 0.005 versus vehicle). A second experiment, examined the therapeutic window for PNU-101017 using the dose level of 30 mg/kg intraperitoneally. Administration of the first of two doses (2 hours apart) at the time of reperfusion resulted in an identical decrease in CA1 damage at 5 days to that seen with preischemic treatment (P < 0.003 versus vehicle). Even with a delay of the initial dosing until 4 hours after reperfusion, PNU-101017 reduced CA1 neuronal loss to only 32% (P < 0.01 versus vehicle). In a third experiment in which the duration of the ischemic insult was increased to 10 minutes and the brains were not analyzed until 28 days after ischemia, daily PNU-101017 dosing for the full 28 days still significantly preserved CA1 neurons, although less effectively than in the milder 5 minute-ischemia model. The loss of dopaminergic nigrostriatal neurons was also reduced. The neuroprotective effect of PNU-101017 was not associated with any overt CNS depression and it did not correlate with hypothermia. This benzodiazepine-receptor partial agonist may have potential for the treatment of global cerebral ischemia.
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PMID:Neuroprotective properties of the benzodiazepine receptor, partial agonist PNU-101017 in the gerbil forebrain ischemia model. 929 May 85


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