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

Considerable controversy exists about whether postischemic hypothermia can permanently salvage hippocampal CA1 neurons or just postpone injury. Studies of very brief cooling in rat have found transient benefit, whereas experiments in gerbil using protracted hypothermia report lasting protection. This discrepancy might be because of the greater efficacy of longer cooling or it might, for example, represent an important species difference. In the present study, a 48-hour period of mild hypothermia was induced starting 6 hours after 10 minutes of severe four-vessel occlusion ischemia in rats. Untreated normothermic ischemia resulted in total CA1 cell loss (99%), whereas delayed hypothermia treatment reduced neuronal loss to 14% at a 28-day survival. In unregulated rats, brain temperature spontaneously fell during ischemia, and stayed subnormal for an extended period after ischemia. This mild cooling resulted in more variable and less severe CA1 injury (75%). Finally, vertebral artery cauterization under halothane anesthesia caused an approximately 2 degrees C drop in brain temperature for 1 hour, but prevention of this hypothermia did not significantly affect CA1 damage. In summary, protracted postischemic hypothermia provided robust and long-term CA1 protection in rat. These results encourage the clinical assessment of prolonged hypothermia and its use as a model to understand ischemic CA1 injury.
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PMID:Indefatigable CA1 sector neuroprotection with mild hypothermia induced 6 hours after severe forebrain ischemia in rats. 1041 28

Experimental studies have demonstrated that postischemic therapeutic interventions may delay rather than provide long-lasting neuroprotection. The purpose of this study was to determine whether mild hypothermia (33-34 degrees C) combined with the anti-inflammatory cytokine interleukin-10 (IL-10) would protect the CA1 hippocampus 2 months after ischemia. Rats were subjected to 12.5 min of normothermic (37 degrees C) forebrain ischemia by two-vessel occlusion followed immediately by: (a) 4 h of normothermic (37 degrees C) reperfusion (n = 5); (b) 4 h of postischemic hypothermia (33-34 degrees C) (n = 5); (c) 4 h of normothermia plus IL-10 (5 micrograms) treatment 30 min after ischemia and at 3 days (n = 5); or (d) 4 h of hypothermia plus IL-10 treatment (n = 5). Rats survived for 2 months and were perfusion fixed for quantitative histopathological assessment of CA1 hippocampus. Postischemic normothermia and hypothermia, as well as normothermia plus IL-10 treatment led to severe damage of the CA1 hippocampus. In contrast, the combined treatment of hypothermia with IL-10 treatment improved overall neuronal survival by 49% compared to normothermic ischemia (P < 0.01). These data emphasize the detrimental consequences of secondary inflammatory responses on ischemic neuronal damage after transient global ischemia. In postinjury settings where restricted durations of mild hypothermia can be induced, anti-inflammatory treatments, including IL-10, may promote chronic neuroprotection.
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PMID:Postischemic hypothermia and IL-10 treatment provide long-lasting neuroprotection of CA1 hippocampus following transient global ischemia in rats. 1041 51

Organotypic brain slices cultured on semi-porous membranes is an increasingly popular in vitro preparation for studying mechanisms of ischemic brain damage. To model in vivo hypoxia, cultured brain slices are exposed to anaerobic atmosphere by placing them into a special incubator. This requirement limits the use of in vitro ischemic models to highly specialized laboratories. Here, we describe a simple method that reproduces hypoxic injury, where cultured hippocampal slices are submerged into glucose-free deoxygenated medium for 1 h. The extent and distribution of hippocampal neuronal loss obtained with this treatment resembled that caused by hypoxia in living tissue in situ, i.e. CA1 pyramidal cell layer was most vulnerable and dentate granular cell layer was least susceptible to hypoxia as measured with fluorescence of the viability marker propidium iodide (PI). Electrophysiologic functional impairment determined by field recordings of CA1 pyramidal neurones temporally coincided with the extent of neuronal death. In addition, known neuroprotective treatments, such as hypothermia and phenytoin application ameliorated neuronal damage in a pattern similar to previously published reports. Therefore, the present in vitro model of ischemia is simple, reliable and of low cost. It is well suited for short and long-term studies of the mechanisms of hypoxic brain damage.
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PMID:A submersion method to induce hypoxic damage in organotypic hippocampal cultures. 1047 80

Hypothermia in clinical use is for protection of the brain during cardiac surgery and resuscitation of post-traumatic brain injury or focal brain ischemia. In the present study, effects of hypothermia on evoked potential, long-term potentiation (LTP) in hippocampal CA1, electroencephalogram (EEG) and cerebral blood flow (CBF) were studied with use of anesthetized rats. In addition to brain function, the changes in systemic blood pressure, heart rate, respiratory metabolism by means of the artery blood gas analysis and end tidal carbon dioxide concentration (ETCO2) were studied. After obtaining baseline recordings of evoked potential at 37 degrees C of brain temperature, rats were cooled by the iceslash-blanket method and were maintained at either 28 degrees C or 32 degrees C. Ninety minutes later, the animals were re-warmed up to 37 degrees C. When temperature was stabilized at 28 degrees C or 32 degrees C, the high-frequent stimulation (tetanus) was delivered. Responses were recorded for 60 minutes following the tetanic stimulation. Both heart rate and mean arterial pressure increased by cooling. CBF was reduced by cooling to 49.0 +/- 6.2% at 28 degrees C and 72.9 +/- 6.9% at 32 degrees C from the baseline. The amplitude of population spike in the hippocampal CA1 region increased to 194.6 +/- 10.6% (28 degrees C) and 168.4 +/- 6.9% (32 degrees C) by cooling. After re-warming, the amplitude was reduced to 146.8 +/- 12.9% in 28 degrees C group and to 131.9 +/- 9.7% in 32 degrees C group, but a significant difference from the baseline remained. The latency increased to 135.48 +/- 2.70% at 28 degrees C and 115.55 +/- 2.26% at 32 degrees C by cooling but recovered to the baseline levels by re-warming. LTP in the hippocampal CA1 was observed at 32 degrees C but not at 28 degrees C. These findings suggest that hypothermia may increase hippocampal synaptic transmission and may not disturb its plasticity at 32 degrees C.
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PMID:[Effects of mild and moderate hypothermia on cerebral function and cerebral circulation of the rat in vivo]. 1049 55

This study was undertaken to evaluate the histological nature of brain damage caused by deep hypothermic circulatory arrest during cardiopulmonary bypass. Total body cooling to 15 degrees C and rewarming were performed with a conventional cardiopulmonary bypass technique using the femoral artery and vein. Dogs were assigned to one of three groups. In group 1 (n = 4), cardiopulmonary bypass was maintained in a state of deep hypothermia (15 degrees C) for 90 min, group 2 animals (n = 5) underwent 60 min of deep hypothermic circulatory arrest at 15 degrees C, and group 3 (n = 6) underwent 90 min of deep hypothermic circulatory arrest at 15 degrees C. All dogs were killed by perfusion fixation 72 h after cardiopulmonary bypass. The CA1 regions of the hippocampi were examined by light and electron microscopy. Biotinylated dUTP was used for nick-end labeling of apoptotic cells mediated by terminal deoxytransferase. No morphological change was observed in group 1 dogs, and very little in group 2 dogs. More severe neuronal damage was observed in group 3. The nuclei of many cells were shrunken and showed nick-end labeling. Dense chromatin masses were detected electron microscopically in the nuclei of CA1 pyramidal cells. Neuronal cell death observed in CA1 pyramidal cells 72 h after 90 min of deep hypothermic circulatory arrest at 15 degrees C involves apoptosis. Therefore, according to this model, the maximum duration of deep hypothermic circulatory arrest should not be allowed to exceed 60 min.
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PMID:Hippocampal neuronal death following deep hypothermic circulatory arrest in dogs: involvement of apoptosis. 1049

Small reductions in temperature have been shown to improve neurologic recovery after ischemia. We have examined the effect of temperature on biochemical and physiological changes during hypoxia using rat hippocampal slices as a model system. The postsynaptic population spike recorded from the CA1 pyramidal cell region of slices subjected to 7 min of hypoxia with hypothermia (34 degrees C) recovered to 73% of its prehypoxic level; slices subjected to the same period of hypoxia at 37 degrees C did not recover. After 7 min of hypoxia ATP fell to 48% of its prehypoxic concentration at 34 degrees C and 30% at 37 degrees C. Potassium fell to 86% during 7 min of hypoxia with hypothermia, this compares to a fall to 58% at 37 degrees C. The increase in sodium after 7 min of hypoxia was also attenuated by hypothermia (133% vs. 163% of its prehypoxic concentration). When the hypoxic period was shortened to 3 min (37 degrees C) the population spike recovered to 94%. If the temperature was increased to 40 degrees C there was only 7% recovery of the population spike after 3 min of hypoxia. With hyperthermia (40 degrees C), ATP fell to 33% after 3 min of hypoxia, this compares to 81% at normothermia. Potassium fell to 76% after 3 min of hypoxia with hyperthermia, this compares to 91% at 37 degrees C. Sodium concentrations increased with hyperthermia before hypoxia, at 3 min of hypoxia there was no significant difference between the hyperthermic and normothermic tissue; there was a large increase in sodium with hyperthermia after 5 min of hypoxia (209% vs. 146%). We conclude that the improved recovery after hypothermic hypoxia is at least in part due to the attenuated changes in ATP, potassium and sodium during hypoxia and that the worsened recovery with hyperthermia is due to an exacerbation of the change in ATP, potassium and sodium concentrations during hypoxia.
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PMID:Effect of small changes in temperature on CA1 pyramidal cells from rat hippocampal slices during hypoxia: implications about the mechanism of hypothermic protection against neuronal damage. 1053 70

Previous cerebral ischemia studies have reported the limitations of restricted periods of postischemic hypothermia in producing long-term neuroprotection. The present experiment attempts to determine whether delayed treatment with the free radical scavenger N-tert-butyl-a-phenylnitrone (PBN) is protective at 2 months following transient global forebrain ischemia, and whether additive effects can be observed when PBN is administered in combination with moderate hypothermia. For this aim rats were subjected to 10 min of two-vessel forebrain ischemia followed by (a) 3 h of postischemic normothermia (37 degrees C); (b) 3 h of postischemic hypothermia (30 degrees C); (c) normothermic procedures combined with delayed injections of PBN (100 mg/kg) on days 3, 5 and 7 post-insult; (d) postischemic hypothermia combined with delayed PBN treatment; or (e) sham procedures. Outcome measures included cognitive behavioral testing and quantitative histopathological analysis at 2 months. Postischemic PBN injections induced a systemic hypothermia (1.5 degrees C-2.0 degrees C) that lasted for 2-2.5 h. Water maze testing revealed significant performance deficits relative to shams in the normothermic ischemic group, with the postischemic hypothermia and PBN groups showing intermediate values. A significant attenuation of cognitive deficits was observed in the animal group receiving the combination postischemic hypothermia and delayed PBN treatment. Quantitative CA1 hippocampal cell counts indicated that each of the ischemia groups exhibited significantly fewer viable CA1 neurons compared to sham controls. However, in rats receiving either delayed PBN treatment or 3 h of postischemic hypothermia, significant sparing of CA1 neurons relative to the normothermic ischemia group was observed. These data indicate that hypothermia combined with PBN treatment provides long-term cognitive improvement compared to nontreatment groups. PBN-induced mild hypothermia could contribute to the neuroprotective effects of this pharmacological strategy.
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PMID:Effects of combined postischemic hypothermia and delayed N-tert-butyl-alpha-pheylnitrone (PBN) administration on histopathologicaland behavioral deficits associated with transient global ischemia in rats. 1055 35

The neuroprotective activity of the non-competitive alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) antagonist GYKI-52466 (1-[4-aminophenyl]-4-methyl-7,8-methylene-dioxy-5H-2,3-benzodia zep ine HCI; EGIS-8159) was studied in the gerbil bilateral carotid occlusion (BCO) model of global ischemia. Drug effect on hippocampal CA1 neuronal loss, hypermotility, and cognitive deficit (decrease in spontaneous alternation (SA) behaviour in the Y-maze) induced by 5-min or 3-min BCO were measured. GYKI-52466 was administered at 4 x 15 mg/kg intraperitoneal (i.p.) doses 30, 45, 60, and 75 min following surgery. The competitive AMPA antagonist NBQX (2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(F)-quinoxaline) applied at 3 x 30 mg/kg i.p. doses 60, 70, and 85 min after reperfusion was also tested for comparison. Both compounds showed weak and non-significant effects on 5-min BCO-induced changes in all the three variables. However, following 3-min ischemia GYKI-52466 and NBQX produced significant inhibition (49% and 48%, respectively) on CA1 cell loss. Moreover, GYKI-52466, but not NBQX, significantly inhibited the 3-min ischemia induced hypermotility and decrease in SA. At their neuroprotective doses, both compounds caused long-lasting (min. 8 h) hypothermia in gerbils. GYKI-52466 induced much higher decrease in body temperature (6 degrees C at peak level) than NBQX did (2 degrees C at peak level). Administration of 4 x 10 mg/kg i.p. chlorpromazine to gerbils 15 min before and 0, 15, and 30 min after 3-min BCO resulted in considerable hypothermia (5.5 degrees C peak effect, 8 h duration), but no protective action of the compound on CA1 cell loss and hypermotility was observed. However, chlorpromazine inhibited the ischemia-induced cognitive impairment. The results suggest that drug-induced hypothermia may differentially influence the histological and the behavioural outcomes of ischemic intervention.
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PMID:The neuroprotective and hypothermic effect of GYKI-52466, a non-competitive alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-antagonist on histological and behavioural variables in the gerbil global ischemia model. 1056 79

In this study, we evaluated the effects of hypothermic exposure on pentylenetetrazol (PTZ) kindling and the resulting deficit of shuttle-box avoidance learning in rats. Additionally, to acknowledge neuronal cell loss, we estimated the number of toluidine blue-positive cells in different brain regions after PTZ kindling and hypothermia exposure in comparison to different normothermic and hypothermic controls. To obtain hypothermic conditions over a period of up to about 3 h, 30 min after PTZ application the animals were treated with 5 mg/kg chlorpromazine (CP) and 25 min later exposed to 15 degrees C cold water for 5 min. Under these conditions the rectal and the striatal temperature were reduced up to a maximum of 5 degrees C. The additional injection of CP did not influence the development of PTZ kindling. Animals treated with PTZ/CP and exposed to hypothermia did not reach the criterion for kindling. Furthermore, this group of animals did not demonstrate any learning deficit. Forty-eight hours after the last kindling application the number of toluidine blue-stained cells was decreased in the investigated brain regions (hippocampal CA1 and CA3 sector, hilus, and cingular cortex) of kindled rats. Hypothermia protected from cell damage in the hippocampal CA3 sector and in the hilus. Results suggest that the inhibiting effect of hypothermia on the development of kindling and the following learning deficit possibly resulted from the suppression of cell damage in distinct brain structures on PTZ-kindled rats.
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PMID:Hypothermia inhibits pentylenetetrazol kindling and prevents kindling-induced deficit in shuttle-box avoidance. 1063 31

Ischemic neuronal injury appears to be mediated by disruption of subcellular ion distribution and, therefore, prevention of ion relocation might be neuroprotective. X-ray microanalysis was used to measure concentrations of Na, K, Ca and other elements in subcellular compartments (e.g., mitochondria) of CA1 neurons from oxygen/glucose-deprived (OGD) hippocampal slices. Results showed that OGD produced progressive loss of ion regulation in CA1 cells. Post-OGD reperfusion with normal media exacerbated the initial ion deregulation. To study neuroprotective mechanisms, we determined the ability of hypothermia (31 degrees C) or ion channel blockade to retard intraneuronal ion disruption induced by OGD/reperfusion. Whereas Ca2+ channel blockade (omega-conotoxin MVIIC, 3 microM) was ineffective, hypothermia and Na+ channel blockers (tetrodotoxin, TTX, 1 microM; lidocaine, 200 microM) reduced ion deregulation in subneuronal compartments. Blockade of glutamate receptors (AMPA, 10 microM; the non-NMDA receptor antagonist CNQX, 10 microM/100 microM glycine; the NMDA receptor antagonist CCP, 100 microM) during OGD/reperfusion provided nearly complete protection. These findings provide a foundation for identifying potential pharmacotherapeutic approaches and for discerning corresponding mechanisms of neuroprotection.
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PMID:Intraneuronal ion distribution during experimental oxygen/glucose deprivation. Routes of ion flux as targets of neuroprotective strategies. 1066 26


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