Effect of mild hypothermia on expression of cortical Mfn2 during cerebral ischemia-reperfusion in rats

Abstract

Objective To evaluate the effect of mild hypothermia on the expression of mitofusin 2 (Mfn2) during cerebral ischemia-reperfusion (I/R) in rats. Methods Sixty healthy clean-grade male Sprague-Dawley rats, aged 8 weeks, weighing 200-250 g, were divided into 3 groups (n=20 each) using a random number table method: sham operation group (group S), group I/R and mild hypothermia group (group H). In I/R and H groups, cerebral I/R was induced by inserting a nylon thread with rounded tip into the right internal carotid artery which was occluded for 2 h and then released for reperfusion.In group H, the surface cooling was started immediately after removing the nylon thread, and the rectal temperature was maintained at 32-34 ℃ for 3 h. The neurological deficit were assessed and scored at 24 and 48 h of reperfusion.Animals were then sacrificed, the cerebral cortex in ischemic area was then removed for determination of the viable neuron count (by HE staining), apoptotic neurons (by TUNEL), and expression of Mfn2 (by Western blot). Apoptosis rate was calculated. Results Compared with group S, the neurological deficit score and apoptosis rate were significantly increased, and the count of viable neurons was decreased, the expression of Mfn2 was down-regulated at each time of reperfusion in I/R and H groups (P<0.05). Compared with group I/R, the neurological deficit score and apoptosis rate were significantly deereased, and the count of viable neurons was increased, and the expression of Mfn2 was up-regulated at each time of reperfusion in group H (P<0.05). Conclusion The mechanism by which mild hypothermia attenuates cerebral I/R injury may be associated with up-regulating the expression of Mfn2 in cerebral cortex of rats. Key words: Hypothermia, induced; Reperfusion injury; Brain; Mitochondrial proteins