C1qc Mediates Blood–Brain Barrier Disruption in a Mouse Model of Intracerebral Haemorrhage Through Microglia‐Derived Migrasomes

Abstract

ABSTRACT Extracellular vesicles (EVs) are essential for intercellular communication and significantly influence neuroimmune responses after intracerebral haemorrhage (ICH). This study elucidates the immune mechanisms underlying secondary brain injury following ICH by identifying microglia‐derived migrasomes. By integrating immune cell clustering analysis from single‐cell RNA sequencing (scRNA‐seq) with Mendelian randomization, we identified five key genes associated with ICH. Further experiments revealed that C1qc accumulates around hematomas, worsening blood‒brain barrier (BBB) disruption through migrasome‐mediated pathways. Our results showed that microglial migrasomes transport C1qc to induce pyroptosis in vascular endothelial cells, thereby compromising BBB integrity. Genetic ablation of C1qc substantially attenuated this BBB damaging effect, C1qc‐deficient migrasomes exhibited protective properties. Our findings, for the first time, reveal the mechanistic role of C1qc and migrasomes in ICH pathogenesis and establish microglia‐derived migrasomes as promising therapeutic targets, providing novel avenues to improve neurologic outcomes after ICH.