Transcriptomic Profile of Microglia Following Inflammation-Sensitized Hypoxic-Ischemic Brain Injury in Neonatal Rats Reveals Strong Contribution to Neutrophil Chemotaxis and Activation
Inflammation-sensitized hypoxic brain injury significantly contributes to neonatal mortality as affected neonates will not benefit from standard cooling treatments. To clarify why treatments fail in this special scenario, we aimed to experimentally investigate the immune response of microglia in an inflammation-sensitized neonatal hypoxia-ischemia (HI) model. Transcriptomic analysis of microglia isolated from brains following inflammation-sensitized HI brain injury revealed a strong upregulation of leukocyte recruitment and pro-inflammatory markers. Specifically, markers associated with neutrophil-mediated immune responses and chemotaxis were upregulated in the inflammation-sensitized HI group compared to the non-inflammation-sensitized HI and control groups. Serpine 1 and Selp could be identified as specifically upregulated markers indicating an acute inflammatory condition before HI injury. Our study revealed a microglia population which is primed to recruit peripheral neutrophils to infiltrate the brain and mediate neutrophil immune response. We showed a strong contribution to neutrophil activation in case of inflammation following hypoxia-ischemia in the brain. Targeting microglia-mediated neutrophil recruitment can indicate a possible treatment approach in case of inflammation-sensitized HI brain injury. Overall design: RNA-seq profiling of mciroglia cells from seven-day-old Wistar rat pubs that underwent hypoxia treatment or sham surgery after LPS- or NaCl-sensitization.