Prolonged Mild Hypothermia Therapy Protects the Brain Against Permanent Focal Ischemia

Abstract

Background and Purpose —The efficacy of hypothermic intervention for permanent focal ischemia has yet to be clarified. This study investigated the effect of a prolonged moderate or mild hypothermia on permanent focal ischemia in rats. Methods —Two permanent focal ischemia models in male Sprague-Dawley rats were used. Moderate (30°C, in experiment 1) or mild (33°C, in experiment 2) hypothermia was achieved at the time of the induction of focal ischemia and was maintained for 2 hours under general anesthesia. Thereafter, the hypothermic condition was maintained by means of a cold room for a total 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 core 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 hypothermia group: 169±33 mm 3 at 48 hours (mean±SEM, P <0.05). In experiment 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 significant differences in neurological function from days 2 through 21 between the two groups. Mean regional cerebral blood flow in the penumbra region increased to a level >50% of baseline. Conclusions —Prolonged mild hypothermia suppressed the development of cerebral infarct and neurological deficit chronically after the induction of permanent focal ischemia.