Effect of mild hypothermia on expression of phosphorylated eukaryotic translation initiation factor 2α in hippocampus in a mouse model of cerebral ischemia-reperfusion

Abstract

Objective To evaluate the effect of mild hypothermia on the expression of phosphorylated eukaryotic translation initiation factor 2α (p-eIf2α) in the hippocampus in a mouse model of cerebral ischemia-reperfusion (I/R). Methods Sixty pathogen-free healthy male C57BL6 mice, aged 8-12 weeks, weighing 20-30 g, were divided into 3 groups (n=20 each) using a random number table: sham operation group (group S), group I/R and mild hypothermia group (group H). Cerebral I/R was induced by 15-min occlusion of bilateral common carotid arteries followed by reperfusion in chloral hydrate-anesthetized mice.Surface cooling was started immediately after reperfusion to maintain the rectal temperature at 32-34 ℃ for 3 h in group H. The neurologic deficit score was evaluated at 24 h of reperfusion.The mice were then sacrificed, brains were immediately removed, and hippocampi were isolated for examination of pathologic changes of hippocampal CA1 region and for determination of neuroapoptosis (by TUNEL) and expression of p-eIf2α (by Western blot). The apoptosis rate was calculated. Results Compared with group S, the neurologic deficit scores at 24 h of reperfusion and apoptosis rate of hippocampal neurons were significantly increased, and the expression of p-eIf2α was up-regulated in I/R and H groups (P<0.05). Compared with group I/R, the neurologic deficit scores at 24 h of reperfusion and apoptosis rate of hippocampal neurons were significantly decreased, and the expression of p-eIf2α was down-regulated in group H (P<0.05). Conclusion Mild hypothermia reduces endoplasmic reticulum stress and inhibits neuroapoptosis through inhibiting the expression of p-eIf2α in the hippocampus in a mouse model of cerebral I/R. Key words: Hypothermia, induced; Brain; Reperfusion injury; Eukaryotic initiation factors; Intracellular signaling peptides and proteins