Unveiling microglia heterogeneity in intracerebral hemorrhage.

Abstract

Microglia are important innate immune cells in the brain, and a rich diversity of subtypes has recently been discovered that expand beyond the traditional classification of traditional M1 (pro-inflammatory) and M2 (anti-inflammatory) classifications. Intracerebral hemorrhage (ICH) is a devastating form of stroke, and the understanding of its later-stage pathological mechanisms remains incomplete. In this study, through the analysis of single-cell transcripts from mice brains 14 days post-ICH, three disease-associated expression patterns of microglia were identified. These include a lipid metabolism and phagocytosis phenotype reminiscent of Disease-Associated Microglia (DAM) initially discovered in Alzheimer's disease models, a phenotype associated with angiogenesis, and a relatively independent phenotype similar to the pro-inflammatory M1 state. These findings were further validated through immunofluorescence in both mouse and human specimens. In addition, analysis of single-cell transcripts from mice brains 3 days post-ICH suggested that microglia involved in lipid metabolism and phagocytosis likely emerge from early proliferating populations. Given the distinct origins and phenotypic characteristics of pro-inflammatory and reparative microglia, interventions targeting these cells hold the potential to modulate the delicate balance between injury and repair during the pathophysiological process of ICH, highlighting a pivotal direction for future therapeutic strategies.