The effect of extending mild hypothermia on focal cerebral ischemia and reperfusion in the rat

Abstract

The aim of the present study is to compare the influence of timing and duration of mild hypothermia on rats subjected to 3 h of middle cerebral artery occlusion followed by 72 h of reperfusion. Sixty-four Sprague-Dawley rats were divided into three mild hypothermic groups according to the duration of mild hypothermia (MHT 32 +/- 0.2 degrees C): intra-ischemia (MHTi); intra-reperfusion (MHTr); and intra-ischemia/ reperfusion (MHTi + r). Our control group was normothermic (NT 37 +/- 0.2 degrees C). Reversible focal cerebral ischemia was carried out in rats with a suture technique. Cerebral blood flow was measured by laser Doppler flowmetry to confirm occlusion and reperfusion. The permeability of the blood-brain barrier was determined by the extravasation of Evans's blue dye, and infarct volumes were measured by 2,3,5-triphenyltetrazolium chloride staining at 72 h after reperfusion. Acute post-ischemic hyperperfusion and delayed hypoperfusion in the ischemic perifocal area and sustained hypoperfusion in the ischemic core were inhibited in MHTi + r and MHTi rats (p < 0.05) as compared to the NT rats. The action of MHTi + r on preventing post-ischemic progressive hypoperfusion in the perifocal area was more effective than that of MHTi 2 h after reperfusion (p < 0.05). Blood-brain barrier disruption in the basal ganglia and cortex areas was significantly reduced in both MHTi + r and MHTi groups, and especially the former. Infarct volume was significantly reduced in both MHTi and MHTi + r groups (p < 0.05). MHTi and MHTi + r have protective effects for reducing ischemia/reperfusion injury. The potential mechanisms may include inhibition of post-ischemic hyperperfusion, and delayed and sustained hypoperfusion.