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- ItemThe alarmin interleukin-1α triggers secondary degeneration through reactive astrocytes and endothelium after spinal cord injury([London] : Nature Publishing Group UK, 2022) Bretheau, Floriane; Castellanos-Molina, Adrian; Bélanger, Dominic; Kusik, Maxime; Mailhot, Benoit; Boisvert, Ana; Vallières, Nicolas; Lessard, Martine; Gunzer, Matthias; Liu, Xiaoyu; Boilard, Éric; Quan, Ning; Lacroix, SteveSpinal 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.