MitoQ attenuates brain damage by polarizing microglia towards the M2 phenotype through inhibition of the NLRP3 inflammasome after ICH

• Published in: Pharmacological research 2020-11, Vol.161, p.105122-105122, Article 105122
• Main Authors: Chen, Weixiang, Guo, Chao, Huang, Suna, Jia, Zhengcai, Wang, Jie, Zhong, Jun, Ge, Hongfei, Yuan, Jichao, Chen, Tunan, Liu, Xin, Hu, Rong, Yin, Yi, Feng, Hua
• Format: Article
• Language: English
• Subjects: Intracerebral haemorrhage; Microglia polarization; Mitochondrial reactive oxygen species; Mitoquinone (MitoQ); NLRP3; Secondary brain injury
• ISSN: 1043-6618; 1096-1186
• DOI: 10.1016/j.phrs.2020.105122

[Display omitted] •MitoQ can prevent brain injury and neurological deficits after ICH in mice.•MitoQ promotes the absorption of haematoma and the integrity of blood-brain barrier after ICH.•MitoQ shifts microglia toward M2 polarization both in vivo and in vitro models of ICH.•MitoQ skrews microglia M2 polarization via inhibiting mitochondrial ROS/NLRP3 pathway. Microglial phenotype plays an important role in secondary injury after intracerebral haemorrhage (ICH), with M1 microglia promoting inflammatory injury and M2 microglia inhibiting neuroinflammation and promoting haematoma absorption. However, there is no effective intervention for regulating the phenotypic transformation of microglia after ICH. This study aimed to elucidate the protective effect of MitoQ, a selective mitochondrial ROS antioxidant, against microglial M1 state polarization and secondary brain injury. The in vivo data showed that MitoQ attenuated neurological deficits and decreased inflammation, oedema and haematoma volume after ICH. In addition, MitoQ decreased the expression of M1 markers and increased the expression of M2 markers both in vivo and in vitro after ICH. Mechanistically, MitoQ blocked overproduction of mitochondrial ROS and activation of the NLRP3 inflammasome in FeCl2-treated microglia. Moreover, NLRP3 siRNA shifted FeCl2-treated microglia from the M1 to the M2 cells, revealing that MitoQ-induce polarization states may be mediated by the mitochondrial ROS/NLRP-3 pathway. In summary, MitoQ alleviates secondary brain injury and accelerates haematoma resolution by shifting microglia towards the M2 phenotype after ICH.