Neuroinflammation is a major contributor to secondary neuronal injury that accounts for a significant proportion of final brain cell loss in neonatal hypoxic-ischemic encephalopathy (HIE). However， the immunological mechanisms that underlie HIE remain unclear. MicroRNA-210 (miR-210) is the master "hypoxamir" and plays a key role in hypoxic-ischemic tissue damage. Herein， we report in an animal model of neonatal rats that HIE significantly upregulated miR-210 expression in microglia in the neonatal brain and strongly induced activated microglia. Intracerebroventricular administration of miR-210 antagomir effectively suppressed microglia-mediated neuroinflammation and significantly reduced brain injury caused... More
Neuroinflammation is a major contributor to secondary neuronal injury that accounts for a significant proportion of final brain cell loss in neonatal hypoxic-ischemic encephalopathy (HIE). However， the immunological mechanisms that underlie HIE remain unclear. MicroRNA-210 (miR-210) is the master "hypoxamir" and plays a key role in hypoxic-ischemic tissue damage. Herein， we report in an animal model of neonatal rats that HIE significantly upregulated miR-210 expression in microglia in the neonatal brain and strongly induced activated microglia. Intracerebroventricular administration of miR-210 antagomir effectively suppressed microglia-mediated neuroinflammation and significantly reduced brain injury caused by HIE. We demonstrated that miR-210 induced microglial M1 activation partly by targeting SIRT1， thereby reducing the deacetylation of the NF-κB subunit p65 and increasing NF-κB signaling activity. Thus， our study identified miR-210 as a novel regulator of microglial activation in neonatal HIE， highlighting a potential therapeutic target in the treatment of infants with hypoxic-ischemic brain injury.
