title: Electroacupuncture Pretreatment Attenuates Cerebral Ischemic Injury via Notch Pathway-Mediated Up-Regulation of Hypoxia Inducible Factor-1α in Rats.
abstract: We have reported electroacupuncture (EA) pretreatment induced the tolerance against focal cerebral ischemia through activation of canonical Notch pathway. However, the underlying mechanisms have not been fully understood. Evidences suggest that up-regulation of hypoxia inducible factor-1α (HIF-1α) contributes to neuroprotection against ischemia which could interact with Notch signaling pathway in this process. Therefore, the current study is to test that up-regulation of HIF-1α associated with Notch pathway contributes to the neuroprotection of EA pretreatment. Sprague-Dawley rats were treated with EA at the acupoint "Baihui (GV 20)" 30 min per day for successive 5 days before MCAO. HIF-1α levels were measured before and after reperfusion. Then, HIF-1α antagonist 2ME2 and γ-secretase inhibitor MW167 were used. Neurologic deficit scores, infarction volumes, neuronal apoptosis, and Bcl2/Bax were evaluated. HIF-1α and Notch1 intracellular domain (NICD) were assessed. The results showed EA pretreatment enhanced the neuronal expression of HIF-1α, reduced infarct volume, improved neurological outcome, inhibited neuronal apoptosis, up-regulated expression of Bcl-2, and down-regulated expression of Bax after reperfusion in the penumbra, while the beneficial effects were attenuated by 2ME2. Furthermore, intraventricular injection with MW167 efficiently suppressed both up-regulation of NICD and HIF-1α after reperfusion. However, administration with 2ME2 could only decrease the expression of HIF-1α in the penumbra. In conclusion, EA pretreatment exerts neuroprotection against ischemic injury through Notch pathway-mediated up-regulation of HIF-1α.
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Anesthesiology, School of Stomatology, The Fourth Military Medical University, Xi'an, 710032, China.|Department of Anesthesiology, Binghua Hospital, Haerbin, 150080, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Anesthesiology, School of Stomatology, The Fourth Military Medical University, Xi'an, 710032, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Deng
authors.affiliation: Department of Anesthesiology, Binghua Hospital, Haerbin, 150080, China.
authors.forename: Yichong
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Anesthesiology, Binghua Hospital, Haerbin, 150080, China.
authors.forename: Lihua
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Department of Anesthesiology, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Yang
authors.affiliation: Institution of Basic Medical Science, Xi'an Medical University, Xi'an, 710032, China.
authors.forename: Xingchun
authors.initials: X
authors.lastname: Gou
authors.affiliation: Department of Anesthesiology, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology, Fuzhou General Hospital, Fuzhou, 350015, China.
authors.forename: Guozhong
authors.initials: G
authors.lastname: Chen
authors.affiliation: Institution of Basic Medical Science, Xi'an Medical University, Xi'an, 710032, China. haoxu83@hotmail.com.
authors.forename: Hao
authors.initials: H
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Anesthesiology, School of Stomatology, The Fourth Military Medical University, Xi'an, 710032, China. xlx116@fmmu.edu.cn.
authors.forename: Lixian
authors.initials: L
authors.lastname: Xu
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism* / Q000517:prevention & control*; D015671:Electroacupuncture / Q000379:methods*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000096:biosynthesis*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D051881:Receptor, Notch1 / Q000502:physiology*; D016896:Treatment Outcome; D015854:Up-Regulation / Q000502:physiology*
chemical_list: C497444:Hif1a protein, rat; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C497763:Notch1 protein, rat; D051881:Receptor, Notch1
keywords: Apoptosis; Electroacupuncture; HIF-1α; Neurobehavior function; Notch pathway; Penumbra; Stroke