NRG-1β exerts neuroprotective effects against ischemia reperfusion-induced injury in rats through the JNK signaling pathway

• Published in: Neuroscience Vol. 362; pp. 13 - 24
• Main Authors: Ji, Yaqing, Teng, Lei, Zhang, Rui, Sun, Jinping, Guo, Yunliang
• Format: Journal Article
• Language: English
• Published: United States Elsevier Ltd 24.10.2017
• Subjects: Animals; Apoptosis - drug effects; Apoptosis - physiology; Brain - drug effects; Brain - enzymology; Brain - pathology; cerebral ischemia reperfusion; Disease Models, Animal; Infarction, Middle Cerebral Artery - drug therapy; Infarction, Middle Cerebral Artery - enzymology; Infarction, Middle Cerebral Artery - pathology; JNK; Male; MAP Kinase Signaling System - drug effects; Myelin Sheath - drug effects; Myelin Sheath - metabolism; Myelin Sheath - pathology; Neuregulin-1 - metabolism; Neuregulin-1 - pharmacology; Neurons - drug effects; Neurons - metabolism; Neurons - pathology; Neuroprotection - drug effects; Neuroprotection - physiology; Neuroprotective Agents - pharmacology; NRG-1β; Random Allocation; Rats, Wistar; Reperfusion Injury - drug therapy; Reperfusion Injury - enzymology; Reperfusion Injury - pathology; rCBF; TTC; BBB; cerebral ischemia reperfusion; H&E; JNK; ACI; DAPI; DCI; LDF; SD; MCAO/R; mNSS; NRG-1β; EB; TEM
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/j.neuroscience.2017.08.032

•NRG-1β improved neurological severity score and brain infarct volume in MCAO/R rats.•NRG-1β protected the morphology and structure of nerve cells in MCAO/R rats.•NRG-1β exhibited a neuroprotective effect via the JNK signaling pathway.•NRG-1β has great potential asa therapeutic strategy for neuroprotection of stroke. Neuregulin-1β (NRG-1β) has great potential to be developed into therapeutics for neuroprotection. The aim of the current study was to analyze the effects and possible signaling pathway of NRG-1β on brain tissues in a rat model of middle cerebral artery occlusion/reperfusion (MCAO/R). In order to observe the protective effect of NRG-1β on MCAO/R, the neurological deficit and infarct volume were measured using a modified neurological severity score (mNSS) test and by triphenyl tetrazolium chloride (TTC) staining. In order to detect the antagonistic effect of NRG-1β on nerve cells and the blood–brain barrier (BBB), the morphology and structure of cortical brain tissues were observed by Evans Blue (EB) staining, hematoxylin–eosin (H&E) and Nissl staining, in situ cell death detection kit, and transmission electron microscopy (TEM). In order to investigate whether NRG-1β exhibited a significant neuroprotective effect via the JNK signaling pathway, the activity of JNK and the levels of phospho-MKK4, phospho-JNK, pan-JNK and phospho-c-Jun were tested using a JNK activity screening kit, immunofluorescent labeling, and western blot analysis, respectively. In the NRG-1β treatment group, accompanied with a decrease in JNK activity, the protein levels of phospho-JNK, phospho-MKK4 and phospho-c-Jun decreased, the ischemia-induced apoptosis decreased, the abnormal morphological structures of nerve cells were ameliorated, the integrity of the BBB was restored, and infarct volume was reduced. At the same time, neurological function was significantly recovered. NRG-1β exerts a neuroprotective effect through the JNK signaling pathway in MCAO/R rats.