Dexmedetomidine Protects Mouse Brain from Ischemia-Reperfusion Injury via Inhibiting Neuronal Autophagy through Up-Regulating HIF-1α

Frontiers in Cellular Neuroscience

Jun Fan¹  Zai-Sheng Qin¹  Cong Luo¹  Quan Zhou¹  Tao Tao¹  Ming-Wen Ouyang²  Shu-Ji Li³  Ying-Ying Fang³ 

[1] Department of Anesthesiology, Nanfang Hospital, Southern Medical UniversityGuangzhou, China;Department of Anesthesiology, The Fifth Affiliated Hospital, Southern Medical UniversityGuangzhou, China;Department of Neurobiology, School of Basic Medical Sciences, Southern Medical UniversityGuangzhou, China;

关键词: dexmedetomidine;    cerebral ischemia;    neuroprotection;    autophagy;    HIF-1α;   

DOI  :  10.3389/fncel.2017.00197

来源: DOAJ

【 摘 要 】

Stroke is the leading cause of death in China and produces a heavy socio-economic burden in the past decades. Previous studies have shown that dexmedetomidine (DEX) is neuroprotective after cerebral ischemia. However, the role of autophagy during DEX-mediated neuroprotection after cerebral ischemia is still unknown. In this study, we found that post-conditioning with DEX and DEX+3-methyladenine (3-MA) (autophagy inhibitor) reduced brain infarct size and improved neurological deficits compared with DEX+RAPA (autophagy inducer) 24 h after transient middle cerebral artery artery occlusion (tMCAO) model in mice. DEX inhibited the neuronal autophagy in the peri-ischemic brain, and increased viability and decreased apoptosis of primary cultured neurons in oxygen-glucose deprivation (OGD) model. DEX induced expression of Bcl-1 and p62, while reduced the expression of microtubule-associated protein 1 light chain 3 (LC3) and Beclin 1 in primary cultured neurons through inhibition of apoptosis and autophagy. Meanwhile, DEX promoted the expression of hypoxia-inducible factor-1α (HIF-1α) both in vivo and in vitro, and 2-Methoxyestradiol (2ME2), an inhibitor of HIF-1α, could reverse DEX-induced autophagic inhibition. In conclusion, our study suggests that post-conditioning with DEX at the beginning of reperfusion protects mouse brain from ischemia-reperfusion injury via inhibition of neuronal autophagy by upregulation of HIF-1α, which provides a potential therapeutic treatment for acute ischemic injury.

【 授权许可】

Unknown