Microglia are an essential component of the neuroprotective scar that forms after spinal cord injury

Victor Bellver-Landete, Floriane Bretheau, Benoit Mailhot, Nicolas Vallières, Martine Lessard, Marie-Eve Janelle, Nathalie Vernoux, Marie-Ève Tremblay, Tobias Fuehrmann, Molly S. Shoichet and Steve Lacroix ()
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Victor Bellver-Landete: Axe neurosciences du Centre de recherche du Centre hospitalier universitaire (CHU) de Québec–Université Laval et Département de médecine moléculaire de l’Université Laval
Floriane Bretheau: Axe neurosciences du Centre de recherche du Centre hospitalier universitaire (CHU) de Québec–Université Laval et Département de médecine moléculaire de l’Université Laval
Benoit Mailhot: Axe neurosciences du Centre de recherche du Centre hospitalier universitaire (CHU) de Québec–Université Laval et Département de médecine moléculaire de l’Université Laval
Nicolas Vallières: Axe neurosciences du Centre de recherche du Centre hospitalier universitaire (CHU) de Québec–Université Laval et Département de médecine moléculaire de l’Université Laval
Martine Lessard: Axe neurosciences du Centre de recherche du Centre hospitalier universitaire (CHU) de Québec–Université Laval et Département de médecine moléculaire de l’Université Laval
Marie-Eve Janelle: Département de biologie-biotechnologie du Cégep de Lévis-Lauzon
Nathalie Vernoux: Axe neurosciences du Centre de recherche du Centre hospitalier universitaire (CHU) de Québec–Université Laval et Département de médecine moléculaire de l’Université Laval
Marie-Ève Tremblay: Axe neurosciences du Centre de recherche du Centre hospitalier universitaire (CHU) de Québec–Université Laval et Département de médecine moléculaire de l’Université Laval
Tobias Fuehrmann: University of Toronto
Molly S. Shoichet: University of Toronto
Steve Lacroix: Axe neurosciences du Centre de recherche du Centre hospitalier universitaire (CHU) de Québec–Université Laval et Département de médecine moléculaire de l’Université Laval

Nature Communications, 2019, vol. 10, issue 1, 1-18

Abstract: Abstract The role of microglia in spinal cord injury (SCI) remains poorly understood and is often confused with the response of macrophages. Here, we use specific transgenic mouse lines and depleting agents to understand the response of microglia after SCI. We find that microglia are highly dynamic and proliferate extensively during the first two weeks, accumulating around the lesion. There, activated microglia position themselves at the interface between infiltrating leukocytes and astrocytes, which proliferate and form a scar in response to microglia-derived factors, such as IGF-1. Depletion of microglia after SCI causes disruption of glial scar formation, enhances parenchymal immune infiltrates, reduces neuronal and oligodendrocyte survival, and impairs locomotor recovery. Conversely, increased microglial proliferation, induced by local M-CSF delivery, reduces lesion size and enhances functional recovery. Altogether, our results identify microglia as a key cellular component of the scar that develops after SCI to protect neural tissue.

Date: 2019
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DOI: 10.1038/s41467-019-08446-0

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