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  • Title: The alarmin interleukin-1α triggers secondary degeneration through reactive astrocytes and endothelium after spinal cord injury.
    Author: Bretheau F, Castellanos-Molina A, Bélanger D, Kusik M, Mailhot B, Boisvert A, Vallières N, Lessard M, Gunzer M, Liu X, Boilard É, Quan N, Lacroix S.
    Journal: Nat Commun; 2022 Oct 02; 13(1):5786. PubMed ID: 36184639.
    Abstract:
    Spinal cord injury (SCI) triggers neuroinflammation, and subsequently secondary degeneration and oligodendrocyte (OL) death. We report that the alarmin interleukin (IL)-1α is produced by damaged microglia after SCI. Intra-cisterna magna injection of IL-1α in mice rapidly induces neutrophil infiltration and OL death throughout the spinal cord, mimicking the injury cascade seen in SCI sites. These effects are abolished through co-treatment with the IL-1R1 antagonist anakinra, as well as in IL-1R1-knockout mice which demonstrate enhanced locomotor recovery after SCI. Conditional restoration of IL-1R1 expression in astrocytes or endothelial cells (ECs), but not in OLs or microglia, restores IL-1α-induced effects, while astrocyte- or EC-specific Il1r1 deletion reduces OL loss. Conditioned medium derived from IL-1α-stimulated astrocytes results in toxicity for OLs; further, IL-1α-stimulated astrocytes generate reactive oxygen species (ROS), and blocking ROS production in IL-1α-treated or SCI mice prevented OL loss. Thus, after SCI, microglia release IL-1α, inducing astrocyte- and EC-mediated OL degeneration.
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