Optimal Depth and Duration of Mild Hypothermia in a Focal Model of Transient Cerebral Ischemia

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Abstract
Background and Purpose—Mild hypothermia is possibly the single most effective method of cerebroprotection developed to date. However, many questions regarding mild hypothermia remain to be addressed before its potential implementation in the treatment of human stroke. Here we report the results of 2 studies designed to determine the optimal depth and duration of mild hypothermia in focal stroke and its effects on infarct size, neurological outcome, programmed cell death, and inflammation. Methods—Rats underwent a 2-hour occlusion of the left middle cerebral artery. In the first study (I) animals were kept (intraischemically) at either 37°C (n=8), 33°C (n=8), or 30°C (n=8). Study II consisted of 4 groups: (1) controls (37°C, n=10), (2) 30 minutes of hypothermia started at ischemic onset (33°C, n=9), (3)1 hour (33°C, n=8), and (4) 2 hours (33°C, n=8). Brain temperature was measured by a thermocouple probe placed in the contralateral cortex. After suture removal, all animals were rewarmed and reperfused for 22 hours (I) or 70 hours (II). Results—Mild hypothermia to 33°C or 30°C was neuroprotective (17±7% and 27±6%, respectively) relative to controls (53±8%, PConclusions—Intraischemic mild hypothermia must be maintained for 1 to 2 hours to obtain optimal neuroprotection against ischemic cell death due to necrosis and apoptosis.