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

To determine which of two treatments for reducing ischemic injury after temporal focal ischemia is more effective, the effects of mild (33 degrees C) intraischemic hypothermia were compared with those of mannitol, the most commonly used neuroprotective agent. Four groups of Sprague-Dawley rats underwent 1 hour of endovascular middle cerebral artery occlusion followed by 23 hours of normothermic reperfusion. The four experimental groups were as follows: Group A, saline control; Group B, mannitol (25%, 1 g/kg); Group C, hypothermia; and Group D, hypothermia plus man-nitol. Laser-Doppler estimates of cortical blood flow showed that hypothermia did not affect blood flow during ischemia or reperfusion. Mannitol increased cortical blood flow during ischemia and reperfusion under both normothermic and hypothermic conditions (p < 0.05). Neurological deficit was significantly less severe in treated rats (Group B, p < 0.05; Group C or D, p < 0.01) than in controls (Group A). Infarct volume, measured on semiserial Nissl-stained sections, was significantly smaller in treated rats (p < 0.01) than in controls. Infarct volume was also significantly smaller in rats treated with hypothermia than in those treated with mannitol (Group C vs. Group B, p < 0.05); there was no difference between rats treated with mannitol and those treated with mannitol and hypothermia. All three treatments reduced infarct area in the ischemic penumbra; hypothermia with or without mannitol also reduced infarct area in the ischemic core. These results demonstrate that both mild intraischemic hypothermia and mannitol reduce infarct size and neurological deficit: hypothermia reduces infarct size more effectively than mannitol, and mannitol adds no significant protection to hypothermia, whereas hypothermia adds significant protection beyond that afforded by mannitol after brief focal ischemia followed by reperfusion in rats. The results suggest that mild intraischemic hypothermia alone, or in combination with mannitol, may be useful in avoiding ischemic injury from temporary vessel occlusion during cerebrovascular surgery.
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PMID:Use of mild intraischemic hypothermia versus mannitol to reduce infarct size after temporary middle cerebral artery occlusion in rats. 778 57

Severe traumatic brain injuries are extremely heterogeneous. At least seven of the secondary derangements in the brain that have been identified as occurring after most traumatic brain injuries also occur after cardiac arrest. These secondary derangements include posttraumatic brain ischemia. In addition, traumatic brain injury causes insults not present after cardiac arrest, i.e., mechanical tissue injury (including axonal injury and hemorrhages), followed by inflammation, brain swelling, and brain herniation. Brain herniation, in the absence of a mass lesion, is due to a still-to-be-clarified mix of edema and increased cerebral blood flow and blood volume. Glutamate release immediately after traumatic brain injury is proven. Late excitotoxicity needs exploration. Inflammation is a trigger for repair mechanisms. In the 1950s and 1960s, traumatic brain injury with coma was treated empirically with prolonged moderate hypothermia and intracranial pressure monitoring and control. Moderate hypothermia (30 degrees to 32 degrees C), but not mild hypothermia, can help prevent increases in intracranial pressure. How to achieve optimized hypothermia and rewarming without delayed brain herniation remains a challenge for research. Deoxyribonucleic acid (DNA) damage and triggering of programmed cell death (apoptosis) by trauma deserve exploration. Rodent models of cortical contusion are being used effectively to clarify the molecular and cellular responses of brain tissue to trauma and to study axonal and dendritic injury. However, in order to optimize therapeutic manipulations of posttraumatic intracranial dynamics and solve the problem of brain herniation, it may be necessary to use traumatic brain injury models in large animals (e.g., the dog), with long-term intensive care. Stepwise measures to prevent lethal brain swelling after traumatic brain injury need experimental exploration, based on the multifactorial mechanisms of brain swelling. Novel treatments have so far influenced primarily healthy tissue; future explorations should benefit damaged tissue in the penumbra zones and in remote brain regions. The prehospital arena is unexplored territory for traumatic brain injury research.
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PMID:Resuscitation from severe brain trauma. 860 6

Although the cerebroprotective effects of hypothermia in focal models of ischemia are undisputed, the underlying mechanisms of this protection are still subject to much controversy. To analyze whether mild hypothermia attenuates glutamate levels in the penumbra surrounding permanent focal infarcts, extracellular glutamate concentration was analyzed bilaterally by microdialysis 20 minutes before to 120 minutes after a middle cerebral artery occlusion (MCAO) in rats. Normothermic animals (n = 11) had a baseline glutamate concentration of 1.14 +/- 0.40 mumol/ml (standard error of the mean) before the MCAO. Extracellular glutamate levels increased gradually after vessel occlusion to peak at 10.1 +/- 1.45 mumol/ml 80 minutes after the MCAO. This level gradually decreased to 5.72 +/- 1.67 mumol/ml by 120 minutes. Hypothermic animals (n = 11) had a baseline glutamate concentration of 1.73 +/- 0.83 mumol/ml before the MCAO. Extracellular glutamate levels increased after vessel occlusion but stabilized at 3.47 +/- 1.37 mumol/ml 30 minutes after the MCAO and remained stable until completion of the experiment. There were no significant differences in cortical blood flow between the normothermic and hypothermic groups at any time during the experiment. Infarct volumes, expressed as a percentage of the volume of the right (ipsilateral) hemisphere, were 19.8 +/- 2.16% in the normothermic group and 13.0 +/- 1.42% in the hypothermic group (P < 0.02). Although the normothermic penumbral glutamate levels began to increase immediately after the MCAO, they did not peak until 80 minutes after occlusion. In contrast, the normothermic core glutamate levels peaked within 30 minutes after the MCAO. Glutamate diffusion from the core region to the penumbra might account for this delay. Hypothermic cerebroprotection might involve a reduction in the pool of potentially diffusable glutamate in the core region but have little direct effect on glutamate release in the penumbra.
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PMID:Mild hypothermia reduces penumbral glutamate levels in the rat permanent focal cerebral ischemia model. 872 54

Despite the enormous scientific efforts that have been made to clarify the pathophysiology of ischemic neuronal injury, the mechanism responsible for neuronal cell death after ischemia remains unclear. Neuronal injury can be roughly classified into three categories: acute ischemic injury, delayed neuronal death and neuronal injury in the penumbra. Flow disturbance known as the noreflow phenomenon and postischemic hypoperfusion is the first limiting factor for neuronal resuscitation after an ischemic insult. Extracorporeal circulation has been tried in an attempt to prevent this blood flow disturbance, but it has become apparent that this is no more effective than conventional resuscitation. Delayed neuronal death seems to be triggered by short exposure to ischemia. Although a molecular mechanism including "glutamate excitotoxicity" has been proposed to explain this phenomenon, the details are still uncertain. The interventional point underlying the protective effect of hypothermia against delayed neuronal death may be the key to understanding its pathophysiology. Neuronal death in the penumbra seems to show deterioration through a mechanism of repeated depolarization "spreading depression", although spreading depression itself has no harmful effect on neurons. The pathophysiological mechanism of spreading depression in combination with flow restriction and other relevant factors related to ischemia remains to be investigated.
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PMID:[The pathophysiology of ischemic neuronal injury: an overview]. 969 85

Hypothermia has proven to be neuroprotective against ischemic brain injury. However, the exact mechanism has not yet been fully understood. In this study, we investigated the effects of hypothermia on cerebral glucose metabolism and blood flow in focal ischemic rats. Rats were divided into normothermic (37+/-0.5 degrees C) and hypothermic (30+/-0.5 degrees C) groups. Focal cerebral ischemia was induced by middle cerebral and ipsilateral common carotid arteries occlusion. Two hours after ischemia, autoradiographic studies of 2-deoxyglucose and iodoantipyrine were performed to measure local cerebral glucose utilization (LCGU) and cerebral blood flow. LCGU in the ischemic core was excessively reduced in both groups. However, a marked increase in LCGU was observed in the boundary zone of the ischemic core in normothermic rats. On the other hand, hyperglycolysis in the boundary zone of the ischemic core was suppressed in hypothermia. This attenuation of hyperglycolysis might be closely related to survival of the ischemic penumbra in hypothermia.
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PMID:Hypothermia attenuates hyperglycolysis in the periphery of ischemic core in rat brain. 980 6

We investigated the effects of acid-base management during pre- and intra-ischemic hypothermia on regional cerebral blood flow (rCBF) and infarct volume using a transient focal cerebral ischemia model. Normal temperature was maintained in a group of 7 anesthetized rats, and hypothermia (30 degrees C) was maintained in two other groups of 7 anesthetized rats, in which alpha-stat (PaCO2 measured at 37 degrees C was maintained at 36 mmHg) and pH-stat (PaCO2 corrected for body temperature was maintained at 36 mmHg) conditions, respectively, were established. rCBF was monitored by laser-Doppler flowmetry in the ischemic penumbra. The middle cerebral artery (MCA) was occluded for 2 h and then reperfused. Infarct volume was measured after 24 h and expressed as a percentage of hemisphere volume. Pre-ischemic hypothermia reduced rCBF in the alpha-stat group and the pH-stat group to 52 +/- 2% and 86 +/- 7%, respectively (p < 0.01). After MCA occlusion, rCBF dropped in the control group, alpha-stat group, and pH-stat group to 57 +/- 11%, 31 +/- 9%, 27 +/- 10%, respectively. Infarct volume in the alpha-stat group, and pH-stat group was significantly smaller (10 +/- 1% and 7 +/- 2%) than in the control group (42 +/- 7%, p < 0.01), but no differences were found between the hypothermic groups. Differences in acid-base management in the present study did not affect infarct volume, but pre-ischemic rCBF in the alpha-stat group was significantly lower than in the pH-stat group. The steeper fall in rCBF after MCA occlusion in the pH-stat group suggested that the autoregulatory response of the collateral pathways may have been reduced in this group.
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PMID:The significance of hypothermic acid-base management induced before ischemia in a rat model of transient middle cerebral artery occlusion. 1010 Feb 9

The data reviewed here suggest the possibility that a global reduction of blood supply to the whole brain or solely to the infratentorial structures down to the range of ischemic penumbra for several hours or a few days may lead to misdiagnosis of irreversible brain or brain stem damage in a subset of deeply comatose patients with cephalic areflexia. The following proposals are advanced: 1) the lack of any set of clinically detectable brain functions does not provide a safe diagnosis of brain or brain stem death; 2) apnea testing may induce irreversible brain damage and should be abandoned; 3) moderate hypothermia, antipyresis, prevention of arterial hypotension, and occasionally intra-arterial thrombolysis may contribute to good recovery of a possibly large subset of cases of brain injury currently regarded as irreversible; 4) confirmatory tests for brain death should not replace or delay the administration of potentially effective therapeutic measures; 5) in order to validate confirmatory tests, further research is needed to relate their results to specific levels of blood supply to the brain. The current criteria for the diagnosis of brain death should be revised.
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PMID:Implications of ischemic penumbra for the diagnosis of brain death. 1058 28

To characterize the development of tissue damage following cryogenic injury to the mouse cortex, the time course of histopathological changes, transcriptional responses and DNA strand breaks following application of a liquid nitrogen-cooled probe to the surface of the parietal bone were assessed. Distinct phases of tissue damage were observed: after 30 min, there was demarcation of a core lesion followed by mainly necrotic cell death starting 2 h after injury. At 12 hours, progressive apoptotic death of scattered cells in the periphery of the core lesion was detected, resembling the penumbra observed in ischaemic stroke. In situ hybridization for c-fos revealed an absence of expression in the core region, suggesting early cessation of transcription. There was strong induction of c-fos in the penumbra 30 min after the lesion, which had spread over the ipsilateral hemisphere at 2 h, possibly caused by peri-infarction depolarization. At later time points, sustained expression of c-fos was observed in some cells in the penumbra. Since a role for c-fos has been postulated in the initiation or execution of apoptotic pathways, the susceptibility of c-fos deficient mice was explored (n=4) in this model. Cryoinjury-induced tissue injury was markedly attenuated in c-fos deficient mice. A model of the phases and mechanisms of cryogenic injury is proposed, which discriminates an early phase characterized by physical changes caused by hypothermia and their immediate consequences (i.e. transcriptional block), an intermediate phase where secondary changes lead to necrosis in the core region, and a final phase of delayed apoptotic cell death in the penumbra.
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PMID:Distinct phases of cryogenic tissue damage in the cerebral cortex of wild-type and c-fos deficient mice. 1063 97

Cerebral ischemia is a frequent and dangerous consequence of some cerebrovascular diseases. Ischaemia may be used also electively in the course of neurosurgery. Therefore new possible ways are sought how to reduce the danger of ischaemia or to prevent it. In the submitted paper some methods of neuroprotection are described and their potential or actual applicability in clinical neurosurgery are discussed. In addition to influencing the brain cell and pretentious methods in the sphere of molecular biology and genetics the induction of systemic hypertension supplemented alternatively by other methods such as hypothermia, the use of mannitol, haemodilution and hypervolaemia seem natural. A higher blood pressure helps to make leptomeningeal and cortical anastomoses patent and strengthens the collateral circulation from marginal zones of ischaemia, penumbra to the ischaemic centre and to prevent thus cerebral infarction.
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PMID:[Cerebral ischemia and neuroprotection from the viewpoint of the neurosurgeon]. 1074 19

Recent studies suggest that mild hypothermia significantly alleviate damage following cerebral ischemia though the precise mechanism is poorly defined. In the present study, middle cerebral artery occlusion (MCAo) was induced in Sprague-Dawley (SD) rats for 1 h followed by varying periods of reperfusion. Cerebral infarcts identified by hematoxylin & eosin (H&E) staining revealed extensive lesion in normothermic (NT) 37 degrees C and small lesion in hypothermic (HT) 33 degrees C group of rats. Immunohistochemical analysis revealed Bcl-2 was induced in many neurons of HT group, while Bax and cytochrome c was induced in few neurons. In situ detection of DNA fragmentation using 3'-OH end labeling method (terminal dUTP nick-end labelling (TUNEL)) indicated, higher number of TUNEL-positive cells in NT group, but significantly decreased in HT group. The expression pattern revealed many neurons at the penumbra region could survive in HT group whereas, many neurons are committed to die in NT group. Our results suggest that hypothermia is selectively interfering at more than one place and providing protection.
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PMID:Immunohistochemical expression of Bcl-2, Bax and cytochrome c following focal cerebral ischemia and effect of hypothermia in rat. 1098 40


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