Dexmedetomidine Attenuates Neonatal Hypoxic–Ischemic Encephalopathy by Inhibiting Microglia Activation Through Upregulating Rbm47

Neonatal hypoxic–ischemic encephalopathy (NHIE) is a leading cause of morbidity and mortality in term infants. The anesthetic dexmedetomidine (Dex) has been shown to reduce brain damage. In this study, hypoxia–ischemia (HI) in neonatal rats caused significant cerebral infarction, neurological deficits, learning and cognitive impairments, inflammatory responses, and microglia polarization. Dex treatment mitigated HI-induced brain injury in rats. Lipopolysaccharide (LPS) increased inflammation in BV2 cells, elevated M1 polarization markers, and raised the proportion of M1 cells. Dex reduced inflammation and M1 polarization in BV2 cells. Rbm47 was identified as a target of Dex, being downregulated in NHIE rat brain tissues and upregulated by Dex. Rbm47 co-localized with microglia and was decreased as the microglia marker Iba-1 increased. Adenovirus-mediated overexpression of Rbm47 alleviated brain injury in NHIE rats and reduced microglial inflammation and M1 activation, both in vitro and in vivo. Conversely, knockdown of Rbm47 hindered the protective effects of Dex against BV2 cell inflammation and M1 polarization. This study indicates that Rbm47 mediates the protective effects of Dex against NHIE brain injury. Graphical Dexmedetomidine upregulates Rbm47, suppressing M1 polarization and inflammation of microglia, thereby alleviating cerebral infarction, neurological deficits, and cognitive impairments in neonatal rats with hypoxic–ischemic encephalopathy.