Use of mild intraischemic hypothermia versus mannitol to reduce infarct size after temporary middle cerebral artery occlusion in rats

Abstract

To determine which of two treatments for reducing ischemic injury after temporal focal ischemia is more effective, the effects of mild (33 degrees C) intraischemic hypothermia were compared with those of mannitol, the most commonly used neuroprotective agent. Four groups of Sprague-Dawley rats underwent 1 hour of endovascular middle cerebral artery occlusion followed by 23 hours of normothermic reperfusion. The four experimental groups were as follows: Group A, saline control; Group B, mannitol (25%, 1 g/kg); Group C, hypothermia; and Group D, hypothermia plus man-nitol. Laser-Doppler estimates of cortical blood flow showed that hypothermia did not affect blood flow during ischemia or reperfusion. Mannitol increased cortical blood flow during ischemia and reperfusion under both normothermic and hypothermic conditions (p < 0.05). Neurological deficit was significantly less severe in treated rats (Group B, p < 0.05; Group C or D, p < 0.01) than in controls (Group A). Infarct volume, measured on semiserial Nissl-stained sections, was significantly smaller in treated rats (p < 0.01) than in controls. Infarct volume was also significantly smaller in rats treated with hypothermia than in those treated with mannitol (Group C vs. Group B, p < 0.05); there was no difference between rats treated with mannitol and those treated with mannitol and hypothermia. All three treatments reduced infarct area in the ischemic penumbra; hypothermia with or without mannitol also reduced infarct area in the ischemic core. These results demonstrate that both mild intraischemic hypothermia and mannitol reduce infarct size and neurological deficit: hypothermia reduces infarct size more effectively than mannitol, and mannitol adds no significant protection to hypothermia, whereas hypothermia adds significant protection beyond that afforded by mannitol after brief focal ischemia followed by reperfusion in rats. The results suggest that mild intraischemic hypothermia alone, or in combination with mannitol, may be useful in avoiding ischemic injury from temporary vessel occlusion during cerebrovascular surgery.