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

Abstract 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.