C1qc Mediates Blood–Brain Barrier Disruption in a Mouse Model of Intracerebral Haemorrhage Through Microglia‐Derived Migrasomes
8 affiliations
- 1Department of Neurosurgery The First Affiliated Hospital of Zhengzhou University Zhengzhou Henan China
- 2Department of Human Anatomy, School of Basic Medical Sciences Zhengzhou University Zhengzhou Henan China
- 3Department of Medical Research & Education Shuang Ho Hospital, Taipei Medical University New Taipei City Taiwan
- 4School of Basic Medical Sciences Zhengzhou University Zhengzhou Henan China
- 5The First Clinical Medical School, Department of Geriatrics Hubei University of Chinese Medicine, Hubei Provincial Hospital of Traditional Chinese Medicine Wuhan Hubei China
- 6Department of Medical Laboratory, Jiujiang Clinical Precision Medicine Research Center Affiliated Hospital of Jiujiang University Jiujiang Jiangxi China
- 7Department of Neurology, Jiujiang Clinical Precision Medicine Research Center Affiliated Hospital of Jiujiang University Jiujiang Jiangxi China
- 8Aging Decoding and Regeneration InstituteSchool of Basic Medical SciencesZhengzhou UniversityZhengzhou Henan China
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.
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BibTeX
@article{li2026c1qc,
title = {{C1qc Mediates Blood–Brain Barrier Disruption in a Mouse Model of Intracerebral Haemorrhage Through Microglia‐Derived Migrasomes}},
author = {Mengyuan Li and Zhihua Li and Dengpan Song and Fang Wang and Mengzhao Feng and Chi‐Tai Yeh and Tingting Zhai and Menghan Deng and Yanyan Sun and Junyang Wang and Xuemei Chen and Yating Wang and Qiong Yang and Moxin Wu and Xiaoping Yin and Junmin Wang and Jian Wang and Fuyou Guo},
journal = {Journal of Extracellular Vesicles},
year = {2026},
month = oct,
doi = {10.1002/jev2.70377},
url = {https://doi.org/10.1002/jev2.70377},
note = {CC BY},
}
RIS
TY - JOUR
TI - C1qc Mediates Blood–Brain Barrier Disruption in a Mouse Model of Intracerebral Haemorrhage Through Microglia‐Derived Migrasomes
AU - Mengyuan Li
AU - Zhihua Li
AU - Dengpan Song
AU - Fang Wang
AU - Mengzhao Feng
AU - Chi‐Tai Yeh
AU - Tingting Zhai
AU - Menghan Deng
AU - Yanyan Sun
AU - Junyang Wang
AU - Xuemei Chen
AU - Yating Wang
AU - Qiong Yang
AU - Moxin Wu
AU - Xiaoping Yin
AU - Junmin Wang
AU - Jian Wang
AU - Fuyou Guo
PY - 2026
DA - 2026/10/26
JO - Journal of Extracellular Vesicles
DO - 10.1002/jev2.70377
UR - https://doi.org/10.1002/jev2.70377
AB - 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.
SN - 2001-3078
ER -