Delayed induction and long-term effects of mild hypothermia in a focal model of transient cerebral ischemia: neurological outcome and infarct size

Object. The goals of this study were to determine the effects of delaying i nduction of mild hypothermia (33 degreesC) after transient focal cerebral i schemia and to ascertain whether the neuroprotective effects of mild hypoth ermia induced during the ischemic period are sustained over time. Methods. In the first study, rats underwent 2 hours of middle cerebral arte ry (MCA) occlusion. Animals in one group were maintained under normothermic conditions (N group, 23 rats) throughout the period of ischemia and reperf usion. Rats in four additional groups were exposed to 2 hours of hypothermi a, which commenced at ischemia onset (H0 group, 11 rats) or with delays of 90 (H90 group, 10 rats), 120 (H120 group, 10 rats), or 180 (H180 group, fiv e rats) minutes, and allowed to survive for 3 days. In the second study, an imals underwent 1.5 hours of MCA occlusion and were maintained under normot hermic (48 rats) or hypothermic (44 rats) conditions during the ischemia pe riod, after which they survived for 3 days, 1 week, or 2 months. All animal s were evaluated for neurological findings at 24 hours and 48 hours postisc hemia and before they were killed. Regions of infarct were determined by ex amining hematoxylin and eosin-stained brain slices obtained at six coronal levels. Conclusions. Mild hypothermia conferred significant degrees of neuroprotect ion in terms of survival, behavioral deficits, and histopathological change s, even when its induction was delayed by 120 minutes after onset of MCA oc clusion (p < 0.05) compared with normothermic conditions. Furthermore, the neuroprotective effect of mild hypothermia (2-hour duration) that was induc ed during the ischemia period was sustained over 2 months. These studies le nd Further support to the use of mild hypothermia in the treatment of strok e.