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Submitted on October 18, 2006
From the Department of Neurology (R.K., S.S.), University of Erlangen, Erlangen, Germany; the Department of Neurology (R.K., T.B., J.L.H., S.S.), University of Heidelberg, Heidelberg, Germany; and the Department of Neurology (D.G.), University of Zurich, Zurich, Switzerland. * To whom correspondence should be addressed. E-mail: rainer.kollmar{at}neuro.imed.uni-erlangen.de.
Background and Purpose--The neuroprotective role of mild therapeutic hypothermia was established in animal models of cerebral ischemia. Still, several issues, including optimal target temperature, remain unclear. The optimal depth of hypothermia in a rat model of focal cerebral ischemia was investigated. Methods--Eighty-four male Wistar rats (n=84) were subjected to filament occlusion of the middle cerebral artery for 90 minutes. Sixty animals were equally split into 6 groups kept at core temperatures of 37°C, 36°C, 35°C, 34°C, 33°C, and 32°C over a period of 4 hours starting 90 minutes after middle cerebral artery occlusion. Twenty-four hours later, after performing a neuroscore, animals were killed and brains examined for infarct size, edema, and invasion of leukocytes. In the second part, 24 animals (8 per group) were kept at 33°C, 34°C, and 37°C for 4 hours, allowed to survive for 5 days, and underwent additional investigation of transferase dUTP nick-end labeling. Results--In the first part, one animal in each treatment group and 2 animals in group 37°C died. The infarct size and edema were smaller for 34°C and 33°C compared with all other groups (P<0.05) over 24 hours. These animals also had better functional outcome (P<0.05) with an advantage for 34°C versus 33°C (P<0.05). Leukocyte count was lower for 34°C and 33°C as compared with the 37°C group. Similar results were obtained in the second part of the study with an advantage for 34°C versus 33°C. Conclusion--Our results suggest that the optimal depth of therapeutic hypothermia in temporary middle cerebral artery occlusion is 34°C.
Revised on November 27, 2006
Accepted on December 6, 2006
Different Degrees of Hypothermia After Experimental Stroke. Short- and Long-Term Outcome
Rainer Kollmar MD*;
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