Neuroprotection by mild hypothermia for temporary or permanent focal ischemia

Abstract

The potential of hypothermic brain protection for ischemic stroke has been demonstrated under laboratory conditions. This article reviews our recent progression understanding the efficacy and specific characteristics of prolonged mild hypothermia for ischemic stroke in rats. Using temporary or permanent focal ischemia models, the rats were treated by mild (33 °C) hypothermia at different schedules. The targeted mild hypothermia was applied only intra- or postischemia, or both periods in the temporary focal ischemia model. In permanent focal ischemia, mild hypothermia was achieved at the onset of ischemia, maintained for 2 h under general anesthesia and further maintained using a cold room for a total of 24 h. The infarcted lesion sizes and neurological function were analyzed for a maximum of 30 days following ischemia and compared to that of the normothermia group. In temporary focal ischemia, the infarcted lesion sizes with intraischemic hypothermia, postischemic hypothermia, or combined prolonged intra- and postischemic hypothermia, analyzed on day 2, were 159 ± 25, 141 ± 19, 76 ± 26 mm3, respectively. The values in the latter two groups were significantly smaller compared to that obtained under normothermia, 211 ± 19 mm3 (mean ± SEM, p< 0.05). The significant difference in lesion sizes and neurological deficits lasted only in the combined hypothermia group on day 30. In permanent focal ischemia, the infarcted lesion 88 ± 15 mm3 in the hypothermia group was significantly small compared to that in normothermia, 211 ± 19 mm3 on day 21 (p< 0.05). Mild hypothermia did suppress the development of cerebral infarction and neurological deficit in temporary or permanent focal ischemia. To obtain the maximum neuroprotection from mild hypothermia, acute and prolonged application of hypothermia are key factors.