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Repair-associated macrophages increase after early-phase microglia attenuation to promote ischemic stroke recovery

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  • Xiaotao Zhang

    (Zhejiang University
    Clinical Research Center for Neurological Diseases of Zhejiang Province
    Chinese Academy of Sciences
    State Key Laboratory of Transvascular Implantation Devices)

  • Huaming Li

    (Zhejiang University
    Clinical Research Center for Neurological Diseases of Zhejiang Province
    State Key Laboratory of Transvascular Implantation Devices)

  • Yichen Gu

    (Zhejiang University
    Clinical Research Center for Neurological Diseases of Zhejiang Province)

  • An Ping

    (Zhejiang University
    Clinical Research Center for Neurological Diseases of Zhejiang Province)

  • Jiarui Chen

    (Zhejiang University
    Clinical Research Center for Neurological Diseases of Zhejiang Province)

  • Qia Zhang

    (Zhejiang University
    Clinical Research Center for Neurological Diseases of Zhejiang Province)

  • Zhouhan Xu

    (Zhejiang University
    Clinical Research Center for Neurological Diseases of Zhejiang Province)

  • Junjie Wang

    (Zhejiang University
    Clinical Research Center for Neurological Diseases of Zhejiang Province)

  • Shenjie Tang

    (Zhejiang University
    Clinical Research Center for Neurological Diseases of Zhejiang Province)

  • Rui Wang

    (Zhejiang University
    Clinical Research Center for Neurological Diseases of Zhejiang Province)

  • Jianan Lu

    (Zhejiang University
    Clinical Research Center for Neurological Diseases of Zhejiang Province
    State Key Laboratory of Transvascular Implantation Devices)

  • Lingxiao Lu

    (Zhejiang University
    Clinical Research Center for Neurological Diseases of Zhejiang Province)

  • Chenghao Jin

    (Zhejiang University
    Clinical Research Center for Neurological Diseases of Zhejiang Province)

  • Ziyang Jin

    (Zhejiang University
    Clinical Research Center for Neurological Diseases of Zhejiang Province)

  • Jianmin Zhang

    (Zhejiang University
    Clinical Research Center for Neurological Diseases of Zhejiang Province
    Zhejiang University
    Binjiang Institute of Zhejiang University)

  • Ligen Shi

    (Zhejiang University
    Clinical Research Center for Neurological Diseases of Zhejiang Province
    Binjiang Institute of Zhejiang University)

Abstract

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.

Suggested Citation

  • Xiaotao Zhang & Huaming Li & Yichen Gu & An Ping & Jiarui Chen & Qia Zhang & Zhouhan Xu & Junjie Wang & Shenjie Tang & Rui Wang & Jianan Lu & Lingxiao Lu & Chenghao Jin & Ziyang Jin & Jianmin Zhang & , 2025. "Repair-associated macrophages increase after early-phase microglia attenuation to promote ischemic stroke recovery," Nature Communications, Nature, vol. 16(1), pages 1-20, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-58254-y
    DOI: 10.1038/s41467-025-58254-y
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