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

Year: 2026

Type: article

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.

Source: Molecular Medicine Reports

DOI: 10.3892/mmr.2026.14064