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Updated: Oct 9, 2025
Identifying Microglia and Peripheral Infiltrating Macrophages in the Injured Spinal Cords Using Flow Cytometry
Published on: June 24, 2025
Unlike Brief Inhibition of Microglia Proliferation after Spinal Cord Injury, Long-Term Treatment Does Not Improve
Gaëtan Poulen1,2, Sylvain Bartolami1, Harun N Noristani1
1MMDN, Univ. Montpellier, EPHE, INSERM, Montpellier, France.
Abstract:
Microglia are major players in scar formation after an injury to the spinal cord. Microglia proliferation, differentiation, and survival are regulated by the colony-stimulating factor 1 (CSF1). Complete microglia elimination using CSF1 receptor (CSF1R) inhibitors worsens motor function recovery after spinal injury (SCI). Conversely, a 1-week oral treatment with GW2580, a CSF1R inhibitor that only inhibits microglia proliferation, promotes motor recovery. Here, we investigate whether prolonged GW2580 treatment further increases beneficial effects on locomotion after SCI. We thus assessed the effect of a 6-week GW2580 oral treatment after lateral hemisection of the spinal cord on functional recovery and its outcome on tissue and cellular responses in adult mice. Long-term depletion of microglia proliferation after SCI failed to improve motor recovery and had no effect on tissue reorganization, as revealed by ex vivo diffusion-weighted magnetic resonance imaging. Six weeks after SCI, GW2580 treatment decreased microglial reactivity and increased astrocytic reactivity. We thus demonstrate that increasing the duration of GW2580 treatment is not beneficial for motor recovery after SCI.
Insights
Prolonging colony-stimulating factor 1 receptor (CSF1R) inhibitor GW2580 treatment for spinal cord injury (SCI) did not improve motor function recovery. Extended treatment failed to enhance tissue repair or locomotion, indicating limited long-term benefits.
Area of Science:
- Neuroscience
- Regenerative Medicine
- Immunology
Background:
- Microglia play a key role in spinal cord injury (SCI) scar formation.
- Colony-stimulating factor 1 (CSF1) signaling regulates microglia.
- CSF1 receptor (CSF1R) inhibitors impact SCI recovery.
Purpose of the Study:
- To investigate the effects of prolonged GW2580 treatment on motor recovery after SCI.
- To determine if extended inhibition of microglia proliferation improves functional outcomes.
- To assess the impact of long-term GW2580 on tissue and cellular responses post-SCI.
Main Methods:
- Adult mice underwent lateral hemisection to induce SCI.
- Mice received oral GW2580 treatment for 6 weeks.
- Functional recovery was assessed, along with tissue reorganization using ex vivo diffusion-weighted MRI.
- Microglial and astrocytic reactivity were analyzed six weeks post-SCI.
Main Results:
- Long-term GW2580 treatment (6 weeks) did not improve motor recovery after SCI.
- Extended inhibition of microglia proliferation did not enhance tissue reorganization.
- GW2580 treatment decreased microglial reactivity but increased astrocytic reactivity at 6 weeks post-SCI.
Conclusions:
- Prolonging GW2580 treatment beyond one week does not offer additional benefits for motor recovery after spinal cord injury.
- The duration of CSF1R inhibition targeting microglia proliferation is critical for therapeutic outcomes.
- Further research is needed to optimize therapeutic strategies for SCI recovery.
