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Previous studies have revealed that redox components participate in the regulation of microglial polarization. Recently, the novel Nrf2 activator omaveloxolone (Omav) has been validated to improve neurological function in patients with neurodegenerative disorders by regulating antioxidant responses. In this study, we examined the efficacy of Omav in ICH. Omav significantly promoted Nrf2 nuclear accumulation and the expression of HO\u20101 and NQO1 in BV2 cells. In addition, both <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic> experiments showed that Omav treatment inhibited M1\u2010like activation and promoted the activation of the M2\u2010like microglial phenotype. Omav inhibited OxyHb\u2010induced ROS generation and preserved the function of mitochondria in BV2 cells. Intraperitoneal administration of Omav improved sensorimotor function in the ICH mouse model. Importantly, these effects were blocked by pretreatment with ML385, a selective inhibitor of Nrf2. Collectively, Omav modulated microglial polarization by activating Nrf2 and inhibiting ROS generation in ICH models, suggesting that it might be a promising drug candidate for the treatment of ICH.<\/jats:p>","DOI":"10.1155\/2022\/4564471","type":"journal-article","created":{"date-parts":[[2022,3,11]],"date-time":"2022-03-11T20:05:06Z","timestamp":1647029106000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["The Novel Nrf2 Activator Omaveloxolone Regulates Microglia Phenotype and Ameliorates Secondary Brain Injury after Intracerebral Hemorrhage in 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