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

Postischemic hypothermia provides long-lasting neuroprotection against glob al cerebral ischemia in adult rats and gerbils, Studies indicate that hypot hermia must be prolonged (e.g., 24 h) to indefatigably salvage hippocampal CA1 neurons. Delayed hypothermia also reduces focal ischemic injury. Howeve r, no study has examined long-term outcome following postischemic hypotherm ia in adult animals. Furthermore, most studies examined only brief hypother mia (e.g., 3 h). Since previous studies may have overestimated long-term be nefit 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 lat er 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 ra ts and one ischemic group controlled their own postischemic temperature whi le another ischemic group was cooled to 34 degrees C for 48 h starting at 3 0 min following the onset of reperfusion, The infarct area was quantified a fter 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 cortica l injury to 110% +/- 10 SD (P < 0.001) while striatal injury was marginally reduced to 79% loss +/- 17 SD (P < 0.05). Delayed hypothermia of only 34 d egrees C provided long-lasting cortical and striatal protection in adult ra ts subjected to a severe MCAo insult. These results strongly support the cl inical assessment of hypothermia in acute stroke. (C) 2000 Academic Press.