Effects of delayed intraischemic and postischemic hypothermia on a focal model of transient cerebral ischemia in rats

Abstract

Background and Purpose - Intraischemic mild hypothermia has been shown to be neuroprotective in reducing cerebral infarction in transient focal ischemia. As a more clinical relevant issue, we investigated the effect of delayed intraischemic and postischemic hypothermia on cerebral infarction in a rat model of reversible focal ischemia. We also examined the effect of hypothermia on the inflammatory response after ischemia-reperfusion to assess the neuroprotective mechanism of brain hypothermia. Methods - Rats were subjected to 2 hours of middle cerebral artery occlusion followed by 22 hours of reperfusion under the following protocols: (1) rats were treated with normothermia (37.0°C, 4 hours) and then housed in room temperature (25°C; 18 hours) and (2) rats were treated with hypothermia (33.0°C, 4 hours, brain temperature modulation was started 30 minutes before the reperfusion) and then housed in cold temperature (5°C, 18 hours). Animals were killed 24 hours after the onset of ischemia. The infarct volume was examined with 2,3,5-triphenyl-tetrazolium chloride staining. The accumulation of polymorphonuclear leukocytes (PMNLs) and the expression of intercellular adhesion molecule-1 mRNA were evaluated in both groups. Results - A significant reduction (P<0.05) in infarct volume was found in the hypothermia group compared with the normothermia group. Compared with the normothermia group, hypothermic treatment also significantly reduced the accumulation of PMNLs (P<0.01) and inhibited the overexpression of intercellular adhesion molecule-1 mRNA at 22 hours of reperfusion after 2 hours of ischemia. Conclusions - Ischemic brain damage can be reduced with delayed intraischemic and prolonged postischemic hypothermia in a focal model of transient cerebral ischemia in rats. The neuroprotective mechanism of hypothermia may be mediated by suppression of PMNL-mediated inflammatory response after ischemia-reperfusion in this model.