Nicotinic Acetylcholine Receptor Alpha7 Subunit Mediates Vagus Nerve Stimulation-Induced Neuroprotection in Acute Permanent Cerebral Ischemia by a7nAchR/JAK2 Pathway

• Published in: Medical science monitor 2017-12, Vol.23, p.6072-6081
• Main Authors: Lu, Xin-Xin, Hong, Zhong-Qiu, Tan, Zhi, Sui, Ming-Hong, Zhuang, Zhi-Qiang, Liu, Hui-Hua, Zheng, Xiu-Yuan, Yan, Tie-Bin, Geng, Deng-Feng, Jin, Dong-Mei
• Format: Article
• Language: English
• Subjects: alpha7 Nicotinic Acetylcholine Receptor - agonists; alpha7 Nicotinic Acetylcholine Receptor - antagonists & inhibitors; alpha7 Nicotinic Acetylcholine Receptor - metabolism; Animal Study; Animals; Brain Injuries - drug therapy; Brain Ischemia - drug therapy; Brain Ischemia - metabolism; Brain Ischemia - therapy; Disease Models, Animal; Infarction, Middle Cerebral Artery - metabolism; Infarction, Middle Cerebral Artery - surgery; Inflammation - drug therapy; Janus Kinase 2 - metabolism; Male; Neuroprotective Agents - therapeutic use; Rats; Rats, Sprague-Dawley; STAT3 Transcription Factor - metabolism; Vagus Nerve - metabolism; Vagus Nerve Stimulation - methods
• ISSN: 1643-3750; 1234-1010; 1643-3750
• DOI: 10.12659/msm.907628

BACKGROUND The role of nicotinic acetylcholine receptor alpha7 subunit (a7nAchR) in the treatment of acute cerebral ischemia by VNS has not been thoroughly clarified to date. Therefore, this study aimed to investigate the specific role of a7nAchR and explore whether this process is involved in the mechanisms of VNS-induced neuroprotection in rats undergoing permanent middle cerebral artery occlusion (PMCAO) surgery. MATERIAL AND METHODS Rats received a7nAChR antagonist (A) or antagonist placebo injection for control (AC), followed by PMCAO and VNS treatment, whereas the a7nAChR agonist (P) was utilized singly without VNS treatment but only with PMCAO pretreatment. The rats were randomly divided into 6 groups: sham PMCAO, PMCAO, PMCAO+VNS, PMCAO+VNS+A, PMCAO+VNS+AC, and PMCAO+P. Neurological function and cerebral infarct volume were measured to evaluate the level of brain injury at 24 h after PMCAO or PMCAO-sham. Moreover, the related proteins levels of a7nAChR, p-JAK2, and p-STAT3 in the ischemic penumbra were assessed by Western blot analysis. RESULTS Rats pretreated with VNS had significantly improved neurological function and reduced cerebral infarct volume after PMCAO injury (p