Inhibiting microglia proliferation after spinal cord injury improves recovery in mice and nonhuman primates - Laboratoire Charles Coulomb (L2C) Accéder directement au contenu
Article Dans Une Revue Theranostics Année : 2021

Inhibiting microglia proliferation after spinal cord injury improves recovery in mice and nonhuman primates

Christophe Goze-Bac

Résumé

No curative treatment is available for any deficits induced by spinal cord injury (SCI). Following injury, microglia undergo highly diverse activation processes, including proliferation, and play a critical role on functional recovery. In a translational objective, we investigated whether a transient pharmacological reduction of microglia proliferation after injury is beneficial for functional recovery after SCI in mice and nonhuman primates. Methods: The colony stimulating factor-1 receptor (CSF1R) regulates proliferation, differentiation, and survival of microglia. We orally administrated GW2580, a CSF1R inhibitor that inhibits microglia proliferation. In mice and nonhuman primates, we then analyzed treatment outcomes on locomotor function and spinal cord pathology. Finally, we used cell-specific transcriptomic analysis to uncover GW2580-induced molecular changes in microglia. Results: First, transient post-injury GW2580 administration in mice improves motor function recovery, promotes tissue preservation and/or reorganization (identified by coherent anti-stokes Raman scattering microscopy), and modulates glial reactivity. Second, post-injury GW2580-treatment in nonhuman primates reduces microglia proliferation, improves motor function recovery, and promotes tissue protection. Finally, GW2580-treatment in mice induced down-regulation of proliferation-associated transcripts and inflammatory associated genes in microglia that may account for reduced neuroinflammation and improved functional recovery following SCI. Conclusion: Thus, a transient oral GW2580 treatment post-injury may provide a promising therapeutic strategy for SCI patients and may also be extended to other central nervous system disorders displaying microglia activation.
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Dates et versions

hal-03475940 , version 1 (11-12-2021)

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Gaëtan Poulen, Emilie Aloy, Claire M Bringuier, Nadine Mestre-Francés, Maïda Cardoso, et al.. Inhibiting microglia proliferation after spinal cord injury improves recovery in mice and nonhuman primates. Theranostics, 2021, 11 (18), pp.8640-8659. ⟨10.7150/thno.61833⟩. ⟨hal-03475940⟩
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