MST4 modulates the neuro-inflammatory response by regulating IκBα signaling pathway and affects the early outcome of experimental ischemic stroke in mice

• Published in: Brain research bulletin 2020-01, Vol.154, p.43-50
• Main Authors: Luan, Di, Zhang, Yuanxiang, Yuan, Lili, Chu, Zhaohu, Ma, Lingsong, Xu, Yang, Zhao, Shoucai
• Format: Article
• Language: English
• Subjects: ERK; Ischemic stroke; IκBα; JNK; MST4
• ISSN: 0361-9230; 1873-2747
• DOI: 10.1016/j.brainresbull.2019.10.011

•MST4 has involved in the pathophysiological process of MCAO in mice.•MST4-AAV improves neurological deficit symptoms in mice after MCAO.•MST4-AAV reduces cerebral infarction volume in mice after MCAO.•MST4-AAV decreased expression of p-IκBα, p-ERK and p-JNK in mice. MST4 limits peripheral, macrophage-dependent inflammatory responses through direct phosphorylation of the adaptor TRAF6; though its role in neuro-inflammation is unclear. We investigated microglia expression of MST4 and whether is attenuates neuro-inflammatory response after cerebral ischemia-reperfusion injury in mice. Adult male C57BL6 mice were subjected to a 90-minute middle cerebral artery occlusion (MCAO) followed by a 72 -h reperfusing. The results showed that MST4 was involved in the pathological process after cerebral ischemia-reperfusion and was expressed in microglia. MST4-Adeno Associated Virus attenuated brain damage after MCAO and reduced expression of p-IκBα, p-ERK and p-JNK, while MST4 shRNA aggravated brain damage after MCAO and increased expression of p-IκBα, p-ERK and p-JNK. Our results show that MST4 inhibits neuro-inflammatory response in cerebral ischemia-reperfusion injury, improves neurological deficits, and reduces cerebral infarction volume in mice. Strategies to enhance MST4 in response to ischemic stroke may be a potential therapeutic strategy.