%0 Journal Article
%T Inhibiting microglia proliferation after spinal cord injury improves recovery in mice and nonhuman primates
%+ Mécanismes moléculaires dans les démences neurodégénératives (MMDN)
%+ Laboratoire Charles Coulomb (L2C)
%+ Institut des Neurosciences de Montpellier (INM)
%A Poulen, Gaëtan
%A Aloy, Emilie
%A Bringuier, Claire, M
%A Mestre-Francés, Nadine
%A Cardoso, Maïda
%A Perez, Jean-Christophe
%A Goze-Bac, Christophe
%A Boukhaddaoui, Hassan
%A Lonjon, Nicolas
%A Gerber, Yannick, N
%A Perrin, Florence, E
%A Artus, Emaëlle V.F.
%< avec comité de lecture
%@ 1838-7640
%J Theranostics
%I Ivyspring International Publisher
%V 11
%N 18
%P 8640-8659
%8 2021-07-31
%D 2021
%R 10.7150/thno.61833
%K spinal cord injury
%K microglia
%K proliferation
%K rodent
%K primates
%Z Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]Journal articles
%X 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.
%G English
%2 https://hal.science/hal-03475940/document
%2 https://hal.science/hal-03475940/file/Poulen_Theranostics_2021.pdf
%L hal-03475940
%U https://hal.science/hal-03475940
%~ INSERM
%~ EPHE
%~ CNRS
%~ MMDN
%~ INM
%~ L2C
%~ PSL
%~ MIPS
%~ BS
%~ UNIV-MONTPELLIER
%~ TEST-DEV
%~ TEST-HALCNRS
%~ EPHE-PSL
%~ UM-2015-2021