title: Neuregulin1β Effects on Brain Tissue via ERK5-Dependent MAPK Pathway in a Rat Model of Cerebral Ischemia-Reperfusion Injury.
abstract: Neuregulin1β (NRG1β), a member of the excitomotor of tyrosine kinase receptor (erbB) family, was recently shown to play a neuroprotective role in cerebral ischemia-reperfusion injury. The present study analyzed the effects and its possible signaling pathway of NRG1β on brain tissues after cerebral ischemia-reperfusion injury. A focal cerebral ischemic model was established by inserting a monofilament thread to achieve middle cerebral artery occlusion, followed by an NRG1β injection via the internal carotid artery. NRG1β injection resulted in significantly improved neurobehavioral activity according to the modified neurological severity score test. Tetrazolium chloridestaining revealed a smaller cerebral infarction volume; hematoxylin-eosin staining and transmission electron microscopy showed significantly alleviated neurodegeneration in the middle cerebral artery occlusion rats. Moreover, expression of phosphorylated MEK5, phosphorylated ERK5, and phosphorylated MEK2C increased after NRG1β treatment, and the neuroprotective effect of NRG1β was attenuated by an injection of the MEK5 inhibitor, BIX02189. Results from the present study demonstrate that NRG1β provides neuroprotection following cerebral ischemia-reperfusion injury via the ERK5-dependent MAPK pathway.
authors.affiliation: Department of Neurology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China.|Institute of Integrated Medicine, Qingdao University Medical College, Qingdao, Shandong, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Gu
authors.affiliation: Institute of Integrated Medicine, Qingdao University Medical College, Qingdao, Shandong, China.
authors.forename: Keli
authors.initials: K
authors.lastname: Ge
authors.affiliation: Institute of Cerebrovascular Diseases, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China.
authors.forename: Cui
authors.initials: C
authors.lastname: Hao
authors.affiliation: Institute of Integrated Medicine, Qingdao University Medical College, Qingdao, Shandong, China.
authors.forename: Yaqing
authors.initials: Y
authors.lastname: Ji
authors.affiliation: Department of Neurology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China. 18661808653@163.com.
authors.forename: Hongyun
authors.initials: H
authors.lastname: Li
authors.affiliation: Institute of Cerebrovascular Diseases, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China. guoqdsd@163.com.
authors.forename: Yunliang
authors.initials: Y
authors.lastname: Guo
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy* / Q000378:metabolism; D048671:MAP Kinase Kinase 5 / Q000037:antagonists & inhibitors / Q000378:metabolism; D020935:MAP Kinase Signaling System; D008297:Male; D048054:Mitogen-Activated Protein Kinase 7 / Q000378:metabolism; D020890:Neuregulin-1 / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
chemical_list: D020890:Neuregulin-1; D018696:Neuroprotective Agents; D047428:Protein Kinase Inhibitors; D048054:Mitogen-Activated Protein Kinase 7; D048671:MAP Kinase Kinase 5; C482565:Map2k5 protein, rat
keywords: Cerebral ischemia; ERK5; Neureglin1β; Rats; Reperfusion