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Electroacupuncture Pretreatment Attenuates Cerebral Ischemic Injury via Notch Pathway-Mediated Up-Regulation of Hypoxia Inducible Factor-1α in Rats.
Cell Mol Neurobiol. 2015 Nov; 35(8):1093-103.CM

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+Show Affiliations

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.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.Department of Anesthesiology, Binghua Hospital, Haerbin, 150080, China.Department of Anesthesiology, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China.Institution of Basic Medical Science, Xi'an Medical University, Xi'an, 710032, China.Department of Anesthesiology, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China.Department of Anesthesiology, Fuzhou General Hospital, Fuzhou, 350015, China.Institution of Basic Medical Science, Xi'an Medical University, Xi'an, 710032, China. haoxu83@hotmail.com.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.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25976178

Citation

Zhao, Yu, et al. "Electroacupuncture Pretreatment Attenuates Cerebral Ischemic Injury Via Notch Pathway-Mediated Up-Regulation of Hypoxia Inducible Factor-1α in Rats." Cellular and Molecular Neurobiology, vol. 35, no. 8, 2015, pp. 1093-103.
Zhao Y, Deng B, Li Y, et al. Electroacupuncture Pretreatment Attenuates Cerebral Ischemic Injury via Notch Pathway-Mediated Up-Regulation of Hypoxia Inducible Factor-1α in Rats. Cell Mol Neurobiol. 2015;35(8):1093-103.
Zhao, Y., Deng, B., Li, Y., Zhou, L., Yang, L., Gou, X., Wang, Q., Chen, G., Xu, H., & Xu, L. (2015). Electroacupuncture Pretreatment Attenuates Cerebral Ischemic Injury via Notch Pathway-Mediated Up-Regulation of Hypoxia Inducible Factor-1α in Rats. Cellular and Molecular Neurobiology, 35(8), 1093-103. https://doi.org/10.1007/s10571-015-0203-9
Zhao Y, et al. Electroacupuncture Pretreatment Attenuates Cerebral Ischemic Injury Via Notch Pathway-Mediated Up-Regulation of Hypoxia Inducible Factor-1α in Rats. Cell Mol Neurobiol. 2015;35(8):1093-103. PubMed PMID: 25976178.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Electroacupuncture Pretreatment Attenuates Cerebral Ischemic Injury via Notch Pathway-Mediated Up-Regulation of Hypoxia Inducible Factor-1α in Rats. AU - Zhao,Yu, AU - Deng,Bin, AU - Li,Yichong, AU - Zhou,Lihua, AU - Yang,Lei, AU - Gou,Xingchun, AU - Wang,Qiang, AU - Chen,Guozhong, AU - Xu,Hao, AU - Xu,Lixian, Y1 - 2015/05/15/ PY - 2015/02/16/received PY - 2015/04/29/accepted PY - 2015/5/16/entrez PY - 2015/5/16/pubmed PY - 2016/7/29/medline KW - Apoptosis KW - Electroacupuncture KW - HIF-1α KW - Neurobehavior function KW - Notch pathway KW - Penumbra KW - Stroke SP - 1093 EP - 103 JF - Cellular and molecular neurobiology JO - Cell Mol Neurobiol VL - 35 IS - 8 N2 - 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. SN - 1573-6830 UR - https://www.unboundmedicine.com/medline/citation/25976178/Electroacupuncture_Pretreatment_Attenuates_Cerebral_Ischemic_Injury_via_Notch_Pathway_Mediated_Up_Regulation_of_Hypoxia_Inducible_Factor_1α_in_Rats_ L2 - https://doi.org/10.1007/s10571-015-0203-9 DB - PRIME DP - Unbound Medicine ER -