Protective Role of MCPIP1 in Brain Injury Following Hypoxic‐Ischemia in Neonatal Mice

Abstract

Neuroinflammation has been implicated with neurodegenerative diseases and acute brain injuries such as stroke. Monocyte chemotactic protein‐1‐induced protein‐1 (MCPIP1) is a multifunction inflammatory modulator known to have pro‐inflammatory or anti‐inflammatory effects depending on the nature of brain injury. However, its role in brain injury after asphyxia in the developing brain has not been studied. Therefore, we explored the role of MCPIP1 in acute neurodegeneration after hypoxic‐ischemia (HI) in the neonatal mouse model. Neonatal C57BL/6 wild type mice at postnatal day 7 (P7) underwent a carotid artery ligation and exposure to hypoxia (8% oxygen) for 42 minutes. After the HI insult, we determined the time‐course and the spatial distribution of MCPIP1 expression in the brain. To determine the impact of MCPIP1 in acute brain damage, we assessed brain tissue loss 1 week post‐HI brain injury in MCPIP1‐deficient versus wild type mice. Western blot analysis was used to determine MCPIP1 protein expression in the brain. Caspase‐3 activity assays were used to determine apoptotic cell death, and immunoflorescent double‐labeling was utilized to determine the scope of neuroinflammation in different types of cells including astrocytes, microglia, and neuronal cells. Our data revealed that MCPIP1 protein is expressed in the neonatal brain and its expression appears to increase 24 hours after HI insult. Immunostaining showed that MCPIP1 expressing cells are present in both neuronal and non‐neuronal cells of the brain, and that there are increased numbers of MCPIP1‐positive cells in the ipsi‐lateral hemisphere compared to the contra‐lateral hemisphere. Furthermore, there was significant change in brain tissue loss after HI in MCPIP‐1‐deficient mice compared with wild‐type mice. Our data suggest that HI brain injury appears to induce expression of MCPIP1, supporting a possible role of MCPIP1 in neuroinflammation after HI.Support or Funding InformationThis study is funded by KCOM‐ Biomedical Graduate Program, Warner/Ferumaturo Grant, and ATSU Start‐up Fund (BHH).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.