Perioperative Dexmedetomidine attenuates brain ischemia reperfusion injury possibly via up-regulation of astrocyte Connexin 43

BMC Anesthesiology

Fang Ye¹  Wenqi Huang¹  Xiaoyang Zheng¹  Ying Li¹  Xiaoying Cai¹  Zhongxing Wang¹  Zhiyi Zuo²  Qin Wang³ 

[1] Department of Anesthesiology, The First Affiliated Hospital, Sun Yat-sen University;Department of Anesthesiology, University of Virginia;Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-Sen University;

关键词: Brain ischemia;    Reperfusion injury;    Dexmedetomidine;    Astrocytes;    Connexin 43;   

DOI  :  10.1186/s12871-020-01211-7

来源: DOAJ

【 摘 要 】

Abstract Background Astrocyte Connexin 43 (Cx43) is essential for the trophic and protective support of neurons during brain ischemia reperfusion (I/R) injury. It is believed that dexmedetomidine participates in Cx43-mediated effects. However, its mechanisms remained unclear. This study aims to address the relationship and regulation among them. Methods Adult male Sprague-Dawley rats were allocated to the 90-min right middle cerebral arterial occlusion with or without dexmedetomidine pretreatment (5 μg/kg). Neurological functions were evaluated and brain lesions, as well as inflammatory factors (IL-1β, IL-6, TNF-α), were assessed. Ischemic penumbral cortex was harvested to determine the expression of astrocyte Cx43. Primary astrocytes were cultured to evaluate the effect of dexmedetomidine on Cx43 after oxygen-glucose deprivation. Results Dexmedetomidine pretreatment attenuated neurological injury, brain lesions and expression of inflammatory factors (IL-1β, IL-6, TNF-α) after brain ischemia (P < 0.05). Astrocyte Cx43 was down-regulated by brain I/R injury, both in vivo and in vitro, which were reversed by dexmedetomidine (P < 0.05). This effect was mediated by the phosphorylation of Akt and GSK-3β. Further studies with LY294002 (PI3K inhibitor) or SB216763 (GSK-3β inhibitor) confirmed the effect of dexmedetomidine on astrocyte Cx43. Conclusions Perioperative dexmedetomidine administration attenuates neurological injury after brain I/R injury, possibly through up-regulation of astrocyte Cx43. Activation of PI3K-Akt-GSK-3β pathway might contribute to this protective effect.

【 授权许可】

Unknown