Effects of mild hypothermia on the expression of Dickkopf-1 in rats＇ brains after focal cerebral ischemia and reperfusion

Abstract

Objective To investigate the effects of mild hypothermia on the expression of Dickkopf-1 （ Dkk- 1 ） in rats＇ brains after focal cerebral ischemia and reperfusion and to explore the molecular mechanism of any neuroprotective effects of mild bypothermia. Methods A focal cerebral ischemia and reperfusion model was established in rats by intraluminal filament occlusion of the middle cerebral artery. The adult rats were randomly divided into four groups： a sham-operation group, a sham-operation plus mild hypothermia group, a model group, and a model plus mild hypothermia group. The expression of Dkk-1 mRNA and protein in the ischemic cortex at different phases after reperfusion were assessed using a reverse transcription polymerase chain reaction （RT-PCR） , Western blotting and immunohistochemical staining. Results There was little expression of Dkk-1 mRNA or its protein in the sham-operation group or in the sham-operation plus mild hypothermia group. Expression of Dkk-1 mRNA and its protein began to increase after 2 h of cerebral ischemia and 3 h of reperfusion, with expression peaking at the 24th h after the start of reperfusion and then decreasing markedly. But expression was still stronger than in the sham-operation group at the 72nd h. At every reperfusion time point, expression of Dkk-1 mRNA and its protein were markedly less in the model plus mild hypothermia group than in the model group. Conclusion Dkk-I probably participates in the pathologic process of injury caused by focal cerebral ischemia and reperfusion. Inhibiting the expression of Dkk-1 after focal cerebral ischemia and reperfusion is partly responsible for the neuroprotective effects of mild hypothermia. Key words: Mild hypothermia; Cerebral ischemia; Reperfusion; Dickkopf-1