Gene

microRNA

Neuroscience

Biology

Hypoxic Ischemic Encephalopathy

Neuroinflammation

Biochemistry

Hypoxia (environmental)

Downregulation and upregulation

Immunology

Genetics

Organic chemistry

Encephalopathy

Microglia

Oxygen

Inflammation

Internal medicine

Brain damage

Medicine

Chemistry

Cellular and Molecular Immunology

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.

MiRNA-210 induces microglial activation and regulates microglia-mediated neuroinflammation in neonatal hypoxic-ischemic encephalopathy