Dexmedetomidine pretreatment inhibits cerebral ischemia/reperfusion-induced neuroinflammation via activation of AMPK

Focal ischemia/reperfusion (I/R) injury induced cerebral inflammation, aggravates brain damage. The aim of the present study was to investigate the protective mechanisms of dexmedetomidine (DEX) on I/R brain injury in rats. Sprague-Dawley rats were divided to seven experimental groups (18 rats/group): Sham surgery; middle cerebral artery occlusion (MCAO) surgery (90 min); DEX10 [10 mu g/kg intraperitoneal (i.p.) injection 30 min prior to MCAO]; DEX50 (50 mu g/kg i.p. 30 min prior to MCAO); DEX100 (100 mu g/kg i.p. 30 min prior to MCAO); DEX50+Yohimbine [YOH; 5 mg/kg 10 min prior to DEX (50 mu g/kg i.p.) administration and MCAO] and YOH (5 mg/kg 40 min prior to MCAO). At 24 h post-MCAO surgery, neurological deficit was examined by staining damaged brain tissues with 2,3,5-triphenyltetrazolium chloride. Neuronal apoptosis in the cerebral cortex was histologically assessed by terminal deoxynucleotidyl-transferase-mediated dUTP nick end labeling staining, and the expression levels of phosphorylated (p)-AMP-activated protein kinase (AMPK; Thr172) was detected by western blotting. In addition, the expression levels of tumor necrosis factor (TNF)- and interleukin (IL)-1 were assessed by ELISA. At days 1, 2 and 5 following I/R, motor functions were assessed by an observer blinded to the study. The brain infarct size, neurological deficit scores, number of apoptotic neurons, expression levels of pro-inflammatory cytokines TNF- and IL-1 were increased following MCAO, whereas the motor function scores were reduced. Pretreatment with DEX prior to MCAO can reverse the effects induced by I/R. Compared with rats in the Sham group, the expression levels of p-AMPK were mildly increased in the MCAO group and highly increased in the three DEX-treatment groups. Pretreatment with YOH reversed the above effects of DEX and produced a similar level of cerebral I/R injury. The results demonstrated that precondition with DEX exhibited anti-inflammatory effects on brain ischemic injury mediated by AMPK signal pathway.