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

Abstract

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.

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Acknowledgements

We thank the animal facility of Loma Linda University (LLU) for providing animal support; the LLU Flow Cytometry Education and Training Core Facility for providing flow cytometry support; and the LLU animal imaging facility for providing MRI support. This work was supported by the National Institutes of Health grants HL118861 (LZ) and NS103017 (LZ).

Author information

B.L. designed and conducted the experiments, analyzed the data, and wrote the manuscript. C.D. and L.H. conducted experiments and analyzed data. X.M. conducted experiments. L.Z. conceived and designed the studies, interpreted the data, and wrote the manuscript.

Correspondence to Bo Li or Lubo Zhang.

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The authors declare no competing interests.

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Li, B., Dasgupta, C., Huang, L. et al. MiRNA-210 induces microglial activation and regulates microglia-mediated neuroinflammation in neonatal hypoxic-ischemic encephalopathy. Cell Mol Immunol (2019) doi:10.1038/s41423-019-0257-6

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Keywords

  • neuroinflammation
  • neonatal hypoxic-ischemic encephalopathy
  • microRNA-210
  • microglial activation
  • SIRT1