Abstract TP335: Divergent Responses of Macrophages and Microglia in the Hemorrhagic Brain

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Abstract

Blood-derived macrophages (MF) and tissue-resident microglia (MG) and are innate immune cells that are responsible for inflammatory responses and tissue repair after intracerebral hemorrhage (ICH). In the past, since activated MF and MG share common cell surface markers in the injured brain, no study has characterized the functional diversity between these two cell types during the pathophysiology of ICH. In this study, we compared the temporal transcriptional changes and the erythrophagocytosis ability of MF and MG in the ICH brain. We used autologous blood injection to induce ICH in male C57/B6 mice. At days 1, 3, 7, and 10 after ICH induction, MF and MG were isolated from the perihematomal region by fluorescence-activated cell sorting, and transcriptional analyses of 780 genes in these two cell types were determined using NanoString nCounter system. In vivo, quantification of erythrophagocytosis by MF and MG was performed by injection of fluorescent-labeled RBC followed by flow cytometry analysis at day 3 post-ICH. We found that 469 genes were detected on at least one time point in either cell population. Principal components analysis revealed complete separation of the MF and MG populations at all time points on PC1 (Figure (A)). Differential gene expression is displayed in the heat map (B). In vivo, MF had greater ability to clear RBCs than MG in the ICH brain (C). In conclusion, MF and MG have distinct transcriptome profiles and effector responses after ICH which provides functional diversity to aid in ICH brain repair.

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