Repair-associated macrophages increase after early-phase microglia attenuation to promote ischemic stroke recovery
Ischemic stroke recovery involves dynamic interactions between the central nervous system and infiltrating immune cells. Peripheral immune cells compete with resident microglia for spatial niches in the brain, but how modulating this balance affects recovery remains unclear. Here, we use PLX5622 to create spatial niches for peripheral immune cells, altering the competition between infiltrating immune cells and resident microglia in male mice following transient middle cerebral artery occlusion (tMCAO). We find that early-phase microglia attenuation promotes long-term functional recovery. This intervention amplifies a subset of monocyte-derived macrophages (RAMf) with reparative properties, characterized by high expression of GPNMB and CD63, enhanced lipid metabolism, and pro-angiogenic activity. Transplantation of RAMf into stroke-affected mice improves white matter integrity and vascular repair. We identify Mafb as the transcription factor regulating the reparative phenotype of RAMf. These findings highlight strategies to optimize immune cell dynamics for post-stroke rehabilitation.
Authors
- Ziyang Jin
- Zhang Qia (ORCID: https://orcid.org/0009-0006-9711-7070)
- Cheng‐Hao Jin (ORCID: https://orcid.org/0000-0003-4431-2623)
- Yichen Gu (ORCID: https://orcid.org/0000-0003-0439-859X)
- Ligen Shi (ORCID: https://orcid.org/0000-0001-7441-6074)
- Shenjie Tang
- Rui Wang (ORCID: https://orcid.org/0000-0003-3825-3620)
- Jianmin Zhang (ORCID: https://orcid.org/0000-0002-3184-1502)
- Huaming Li (ORCID: https://orcid.org/0000-0002-9538-5358)
- Xiaotao Zhang (ORCID: https://orcid.org/0000-0002-5751-5633)
- Jiarui Chen (ORCID: https://orcid.org/0000-0001-6978-9968)
- Liqin Lu (ORCID: https://orcid.org/0009-0006-4473-5561)
- Jijun Wang (ORCID: https://orcid.org/0000-0003-4536-9664)
- Zhouhan Xu
- Jianan Lü (ORCID: https://orcid.org/0000-0002-6383-506X)
- An Ping
Institutions
- Zhejiang Cancer Hospital (CN)
- Zhejiang Medical and Health Group Hangzhou Hospital (CN)
- Neurological Surgery (US)
- Second Affiliated Hospital of Zhejiang University (CN)
- Zhejiang University-University of Edinburgh Institute (CN)
- Zhejiang University (CN)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-03-31
- DOI
- https://doi.org/10.1038/s41467-025-58254-y
- Citations
- 25
- Primary Topic
- Neuroinflammation and Neurodegeneration Mechanisms
- Type
- article
- Field-Weighted Citation Impact
- 20.21
Funders
- National Natural Science Foundation of China
- Natural Science Foundation of Zhejiang Province