Microglia promote infiltration and polarization of macrophages in cerebral ischemia‑reperfusion via the reactive oxygen species‑SPI1‑CCL9 axis&nbsp;

Kuang,Xianfeng; Peng,Zhangxiang; Yang,Yao; Pu,Shaoquan; Zhang,Mou; Wang,Jiayue; Tao,Jun; Li,Shixiang; Zhan,Dong

doi:10.3892/mmr.2026.14064

January-2027 Volume 35 Issue 1

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January-2027 Volume 35 Issue 1

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Microglia promote infiltration and polarization of macrophages in cerebral ischemia‑reperfusion via the reactive oxygen species‑SPI1‑CCL9 axis

Authors:
- Xianfeng Kuang
- Zhangxiang Peng
- Yao Yang
- Shaoquan Pu
- Mou Zhang
- Jiayue Wang
- Jun Tao
- Shixiang Li
- Dong Zhan
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Affiliations: Department of Orthopaedics, 920th Hospital of Joint Logistics Support Force, Kunming Medical University, Kunming, Yunnan 650032, P.R. China, Department of Geriatrics III, Jiujiang Fifth People's Hospital, Jiujiang, Jiangxi 332000, P.R. China, Department of Intensive Care Medicine, Jiangxi Fengcheng Hospital of Traditional Chinese Medicine, Yichun, Jiangxi 331100, P.R. China, Department of Orthopaedics, 920th Hospital of Joint Logistics Support Force, Kunming Medical University, Kunming, Yunnan 650032, P.R. China, School of Basic Medical Sciences, Kunming Medical University, Kunming, Yunnan 650500, P.R. China, The First Clinical Medical College, Yunnan University of Chinese Medicine, Kunming, Yunnan 650500, P.R. China, Yunnan Key Laboratory of Stem Cell and Regenerative Medicine, School of Rehabilitation, Kunming Medical University, Kunming, Yunan 650500, P.R.China, School of Pharmaceutical Sciences, Kunming Medical University, Kunming, Yunan 650500, P.R. China

Copyright: © Kuang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
Article Number: 6
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Published online on: November 6, 2026

https://doi.org/10.3892/mmr.2026.14064
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Abstract

The aim of the present study was to investigate the role of microglia in promoting macrophage infiltration and polarization during cerebral ischemia‑reperfusion (I/R) injury through the reactive oxygen species (ROS)‑Spi‑1 proto‑oncogene (SPI1)‑chemokine (C‑C motif) ligand 9 (CCL9) signalling axis. Using a cerebral I/R in vitro and in vivo model, microglial activation and macrophage dynamics were assessed. ROS levels were quantified, and SPI1 expression in microglia was analysed. CCL9 secretion was measured, and its impact on macrophage migration and polarization was evaluated in vitro. CCL9 antibody and RNA interference approaches were used to interrogate the signalling pathway. Following cerebral I/R, microglial activation led to increased ROS production, and increased SPI1 and CCL9 expression. This, in turn, increased CCL9 secretion, which attracted macrophages to the site of ischemia and promoted their polarization towards a pro‑inflammatory phenotype. Inhibition of the ROS‑SPI1‑CCL9 axis significantly reduced macrophage infiltration and altered their polarization state. The results of the present study demonstrated that microglia facilitated macrophage infiltration and polarization in cerebral I/R via the ROS‑SPI1‑CCL9 axis, highlighting a potential therapeutic target for mitigating neuroinflammatory damage after a cerebral ischemic stroke.

Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Microglia promote infiltration and polarization of macrophages in cerebral ischemia‑reperfusion via the reactive oxygen species‑SPI1‑CCL9 axis

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