Persistent neuroprotection with prolonged postischemic hypothermia in adult rats subjected to transient middle cerebral artery occlusion.

Postischemic hypothermia provides long-lasting neuroprotection against global cerebral ischemia in adult rats and gerbils. Studies indicate that hypothermia must be prolonged (e.g., 24 h) to indefatigably salvage hippocampal CA1 neurons. Delayed hypothermia also reduces focal ischemic injury. However, no study has examined long-term outcome following postischemic hypothermia in adult animals. Furthermore, most studies examined only brief hypothermia (e.g., 3 h). Since previous studies may have overestimated long-term benefit and have likely used suboptimal durations of hypothermia, we examined whether prolonged cooling would attenuate infarction at a 2-month survival time following middle cerebral artery occlusion (MCAo) in rats. Adult male Wistar rats were implanted with telemetry brain temperature probes and later subjected to 30 min of normothermic MCAo (contralateral to side of probe placement) or sham operation. Ischemia was produced by the insertion of an intraluminal suture combined with systemic hypotension (60 mm Hg). Sham rats and one ischemic group controlled their own postischemic temperature while another ischemic group was cooled to 34 degrees C for 48 h starting at 30 min following the onset of reperfusion. The infarct area was quantified after a 2-month survival time. Normothermic MCAo resulted in almost complete striatal destruction (91% loss +/- 12 SD) with extensive cortical damage (36% +/- 16 SD). Delayed hypothermia treatment significantly reduced cortical injury to 10% +/- 10 SD (P < 0.001) while striatal injury was marginally reduced to 79% loss +/- 17 SD (P < 0.05). Delayed hypothermia of only 34 degrees C provided long-lasting cortical and striatal protection in adult rats subjected to a severe MCAo insult. These results strongly support the clinical assessment of hypothermia in acute stroke.