Intraischemic hypothermia attenuates neutrophil infiltration in the rat neocortex after focal ischemia-reperfusion injury

OBJECTIVE: The mechanisms by which hypothermia influences postischemic outcome remain a matter of discussion. One mechanism thought to play an important role in neuronal damage after ischemia/reperfusion is the accumulation of polymorphonuclear leukocytes in compromised brain tissue. To better understand the potential impact of hypothermia on this injurious mechanism, the present study examined the effect of intraischemic hypothermia on polymorphonuclear leukocyte accumulation after transient focal ischemia. METHODS: The effect of intraischemic hypothermia (30 degrees C) on the accumulation of polymorphonuclear leukocytes was quantified by measuring myeloperoxidase (MPO) activity in the neocortex of Sprague-Dawley rats. Reversible focal ischemia was created by subjecting rats to temporary occlusion of the left middle cerebral artery and both carotid arteries for 3 hours; animals were killed 24 hours after reperfusion. RESULTS: Normothermic animals exhibited significantly greater MPO activity in the infarction core (P < 0.05) and the pericore areas (P < 0.05), compared with corresponding areas in sham-operated animals. Hypothermic animals exhibited significantly greater MPO activity in the core (P < 0.05) but not in the pericore region, compared with sham-operated animals. MPO activity in the pericore region of the hypothermic group was significantly less than that observed in the corresponding region of the normothermic group (P < 0.01). In addition, the total volume of cerebral infarction was reduced by 59% in the hypothermic group. CONCLUSION: These findings demonstrate that intraischemic hypothermia attenuates the inflammatory response to transient focal ischemia in the pericore region, i.e., the region spared from infarction under hypothermic conditions. The findings raise the possibility that a reduction in the inflammatory response after ischemia/reperfusion contributes to the neuroprotective effects of hypothermia.