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Updated: May 22, 2025
Intravital Imaging of Axonal Interactions with Microglia and Macrophages in a Mouse Dorsal Column Crush Injury
Published on: November 23, 2014
Centripetal migration and prolonged retention of microglia promotes spinal cord injury repair
Jianan Ye1, Fangli Shan1, Xinzhong Xu1,2
1Department of Orthopaedics, The Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, China.
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.
Insights
Enhancing microglial migration and retention via CX3CL1 and M-CSF boosts spinal cord injury repair. This strategy optimizes wound healing and axonal regrowth, crucial for locomotor recovery after SCI.
Area of Science:
- Neuroscience
- Immunology
- Regenerative Medicine
Background:
- Neonatal microglia are vital for spinal cord injury (SCI) repair, including wound healing and axonal regeneration.
- Limited microglia migration to adult lesion centers hinders their therapeutic potential in SCI recovery.
Purpose of the Study:
- To investigate methods for enhancing microglial migration and retention at SCI lesion sites.
- To evaluate the impact of targeted chemokine and growth factor delivery on SCI outcomes.
Main Methods:
- Developed a mouse model of SCI involving in situ injection of C-X3-C motif chemokine ligand 1 (CX3CL1) and macrophage colony-stimulating factor (M-CSF).
- Assessed wound healing, axonal preservation/regrowth anatomically, and locomotor function recovery using kinematics analysis.
- Utilized C-X3-C motif chemokine receptor 1 (CX3CR1)-deficient mice to confirm the mechanism of action.
Main Results:
- Decreased CX3CL1 expression and perilesional distribution limit microglial centripetal migration in SCI.
- CX3CL1 alone promoted migration but did not improve functional recovery.
- Combined CX3CL1 and M-CSF enhanced microglial migration and retention, improved wound healing, axonal preservation/regrowth, and locomotor function, an effect dependent on CX3CR1 signaling and potentially involving spleen tyrosine kinase (SYK).
Conclusions:
- Microglial location and abundance are critical for orchestrating spinal cord injury repair.
- Centripetal microglial dynamics represent a promising therapeutic target for SCI interventions.
