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

• Published in: Frontiers in cellular neuroscience Vol. 11; p. 197
• Main Authors: Luo, Cong, Ouyang, Ming-Wen, Fang, Ying-Ying, Li, Shu-Ji, Zhou, Quan, Fan, Jun, Qin, Zai-Sheng, Tao, Tao
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Research Foundation 06.07.2017; Frontiers Media S.A
• Subjects: Anesthesiology; Apoptosis; Autophagy; Brain injury; Carotid arteries; Cerebral blood flow; cerebral ischemia; dexmedetomidine; Glucose; HIF-1α; Hypoxia; Hypoxia-inducible factors; Ischemia; Kinases; Laboratory animals; Microtubule-associated protein 1; Neurological diseases; Neuroprotection; Neuroscience; Neurosciences; Oxygen; Phagocytosis; Proteins; Reperfusion; Rodents; Traumatic brain injury; Veins & arteries; China; dexmedetomidine; HIF-1α; autophagy; cerebral ischemia; neuroprotection
• ISSN: 1662-5102; 1662-5102
• DOI: 10.3389/fncel.2017.00197

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 and , 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.