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Background <p>Recent studies have confirmed the critical role of neonatal microglia in wound healing and axonal regeneration following spinal cord injury (SCI). However, the limited migration of microglia to the center of adult lesion may significantly impede their potential benefits.</p> Methods <p>We established a model of microglial centripetal migration and prolonged retention in C57BL/6J and transgenic mice by injecting exogenous C-X3-C motif chemokine ligand 1 (CX3CL1) and macrophage colony-stimulating factor (M-CSF) directly into the lesion site post-SCI. Wound healing and axonal preservation/regrowth was assessed anatomically, and kinematics analysis was conducted to determine the recovery of locomotor function.</p> Results <p>We identified decreased expression and perilesional distribution of CX3CL1 as the primary reason for the limited centripetal migration of microglia. In situ injection of CX3CL1 into the lesion core promoted microglial centripetal migration, but alone did not improve functional recovery. Nevertheless, a combinational administration of CX3CL1 and M-CSF fostered both centripetal migration and prolonged retention of microglia, thereby effectively displacing blood-derived macrophage infiltration and optimizing wound healing and axonal preservation/regrowth after SCI. Notably, the beneficial effects of CX3CL1 and M-CSF co-administration were specifically blocked in C-X3-C motif chemokine receptor 1 (CX3CR1)-deficient mice. These phenomena may be related to the increase in spleen tyrosine kinase (SYK) levels, which boosts centripetal microglial phagocytosis.</p> Conclusion <p>Our study uncovers the criticality of microglial location and abundance in orchestrating SCI repair, highlighting centripetal microglial dynamics as valuable targets for therapeutic intervention.</p>

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Centripetal migration and prolonged retention of microglia promotes spinal cord injury repair

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年3月12日

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  • Jianan Ye,
  • Fangli Shan,
  • Xinzhong Xu,
  • Chao Liang,
  • Ningyuan Zhang,
  • Hao Hu,
  • Jianjian Li,
  • Fangru Ouyang,
  • Jingwen Wang,
  • Yuanzhe Zhao,
  • Zhida Ma,
  • Congpeng Meng,
  • Ziyu Li,
  • Shuisheng Yu,
  • Juehua Jing,
  • Meige Zheng

摘要

Background

Recent studies have confirmed the critical role of neonatal microglia in wound healing and axonal regeneration following spinal cord injury (SCI). However, the limited migration of microglia to the center of adult lesion may significantly impede their potential benefits.

Methods

We established a model of microglial centripetal migration and prolonged retention in C57BL/6J and transgenic mice by injecting exogenous C-X3-C motif chemokine ligand 1 (CX3CL1) and macrophage colony-stimulating factor (M-CSF) directly into the lesion site post-SCI. Wound healing and axonal preservation/regrowth was assessed anatomically, and kinematics analysis was conducted to determine the recovery of locomotor function.

Results

We identified decreased expression and perilesional distribution of CX3CL1 as the primary reason for the limited centripetal migration of microglia. In situ injection of CX3CL1 into the lesion core promoted microglial centripetal migration, but alone did not improve functional recovery. Nevertheless, a combinational administration of CX3CL1 and M-CSF fostered both centripetal migration and prolonged retention of microglia, thereby effectively displacing blood-derived macrophage infiltration and optimizing wound healing and axonal preservation/regrowth after SCI. Notably, the beneficial effects of CX3CL1 and M-CSF co-administration were specifically blocked in C-X3-C motif chemokine receptor 1 (CX3CR1)-deficient mice. These phenomena may be related to the increase in spleen tyrosine kinase (SYK) levels, which boosts centripetal microglial phagocytosis.

Conclusion

Our study uncovers the criticality of microglial location and abundance in orchestrating SCI repair, highlighting centripetal microglial dynamics as valuable targets for therapeutic intervention.