Prolonged mild hypothermia therapy protects the brain against permanent focal ischemia

Background and Purpose-The efficacy of hypothermic intervention for permane nt focal ischemia has yet to be clarified. This study investigated the effe ct of a prolonged moderate or mild hypothermia on permanent focal ischemia in rats. Methods-Two permanent focal ischemia models in male Sprague-Dawley rats wer e used. Moderate (30 degreesC, in experiment 1) or mid (33 degreesC, in exp eriment 2) hypothermia was achieved at the time of the induction of focal i schemia and was maintained for 2 hours under general anesthesia. Thereafter , the hypothermic condition was maintained by means of a cold room for a to tal of 24 hours. The infarct volume and neurological function were analyzed for a maximum of 21 days and compared with that of the normothermia group. Regional cerebral blood flow was monitored for 6 hours in the ischemic cor e and penumbra region. Results-In experiment 1, the total infarct volume in the normothermic group was 368+/-59 mm(3); In contrast, it was significantly smaller in the hypot hermia group: 169+/-33 mm(3) at 48 hours (mean+/-SEM, P<0.05). In experimen t 2, the infarct volume was 211+/-19 mm(3) in the normothermia group and 88 +/-15 mm(3) in the hypothermia group at 21 days (P<0.05). There were signif icant differences in neurological function from days 2 through 21 between t he two groups. Mean regional cerebral blood flow in the penumbra region inc reased to a level >50% of baseline. Conclusions-Prolonged mild hypothermia suppressed the development of cerebr al infarct and neurological deficit chronically after the induction of perm anent focal ischemia.