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

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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)

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.

Suggested Citation

  • Victor Bellver-Landete & Floriane Bretheau & Benoit Mailhot & Nicolas Vallières & Martine Lessard & Marie-Eve Janelle & Nathalie Vernoux & Marie-Ève Tremblay & Tobias Fuehrmann & Molly S. Shoichet & S, 2019. "Microglia are an essential component of the neuroprotective scar that forms after spinal cord injury," Nature Communications, Nature, vol. 10(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-08446-0
    DOI: 10.1038/s41467-019-08446-0
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    Cited by:

    1. Yongheng Fan & Xianming Wu & Sufang Han & Qi Zhang & Zheng Sun & Bing Chen & Xiaoyu Xue & Haipeng Zhang & Zhenni Chen & Man Yin & Zhifeng Xiao & Yannan Zhao & Jianwu Dai, 2023. "Single-cell analysis reveals region-heterogeneous responses in rhesus monkey spinal cord with complete injury," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    2. Faith H. Brennan & Yang Li & Cankun Wang & Anjun Ma & Qi Guo & Yi Li & Nicole Pukos & Warren A. Campbell & Kristina G. Witcher & Zhen Guan & Kristina A. Kigerl & Jodie C. E. Hall & Jonathan P. Godbout, 2022. "Microglia coordinate cellular interactions during spinal cord repair in mice," Nature Communications, Nature, vol. 13(1), pages 1-20, December.
    3. Wanjie Wu & Yingzhu He & Yujun Chen & Yiming Fu & Sicong He & Kai Liu & Jianan Y. Qu, 2024. "In vivo imaging in mouse spinal cord reveals that microglia prevent degeneration of injured axons," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    4. Floriane Bretheau & Adrian Castellanos-Molina & Dominic Bélanger & Maxime Kusik & Benoit Mailhot & Ana Boisvert & Nicolas Vallières & Martine Lessard & Matthias Gunzer & Xiaoyu Liu & Éric Boilard & Ni, 2022. "The alarmin interleukin-1α triggers secondary degeneration through reactive astrocytes and endothelium after spinal cord injury," Nature Communications, Nature, vol. 13(1), pages 1-22, December.
    5. Noah R. Johnson & Peng Yuan & Erika Castillo & T. Peter Lopez & Weizhou Yue & Annalise Bond & Brianna M. Rivera & Miranda C. Sullivan & Masakazu Hirouchi & Kurt Giles & Atsushi Aoyagi & Carlo Condello, 2023. "CSF1R inhibitors induce a sex-specific resilient microglial phenotype and functional rescue in a tauopathy mouse model," Nature Communications, Nature, vol. 14(1), pages 1-23, December.
    6. Isaac Francos-Quijorna & Marina Sánchez-Petidier & Emily R. Burnside & Smaranda R. Badea & Abel Torres-Espin & Lucy Marshall & Fred Winter & Joost Verhaagen & Victoria Moreno-Manzano & Elizabeth J. Br, 2022. "Chondroitin sulfate proteoglycans prevent immune cell phenotypic conversion and inflammation resolution via TLR4 in rodent models of spinal cord injury," Nature Communications, Nature, vol. 13(1), pages 1-23, December.

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