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

Wang,Zhenhong; Zhou,Wei; Dong,Haiping; Ma,Xiaoxiao; He,Zhenzhou

doi:10.3892/mmr.2018.9349

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

Authors:
- Zhenhong Wang
- Wei Zhou
- Haiping Dong
- Xiaoxiao Ma
- Zhenzhou He
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Affiliations: Department of Anesthesiology, South Campus, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 201112, P.R. China
Published online on: August 3, 2018 https://doi.org/10.3892/mmr.2018.9349
Pages: 3957-3964

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Abstract

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 µg/kg intraperitoneal (i.p.) injection 30 min prior to MCAO]; DEX50 (50 µg/kg i.p. 30 min prior to MCAO); DEX100 (100 µg/kg i.p. 30 min prior to MCAO); DEX50+Yohimbine [YOH; 5 mg/kg 10 min prior to DEX (50 µg/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)‑α and interleukin (IL)‑1β 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‑α and IL‑1β 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.

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