Steve Lacroix<\/a>\u2019s research team found that endogenous inflammatory mediators called interleukin (IL)-1\u03b1 is released by microglia after a spinal cord injury (SCI) and induces inflammation as well as oligodendrocytes\u2019 death. The team was thus interested in understanding how (IL)-1\u03b1 causes its toxic effects on myelin after SCI and what are the consequences.<\/p>\n\n\n\nMethodology<\/h2>\n\n\n\n
Researchers first injected a recombinant form of IL-1\u03b1 in the cerebrospinal fluid of mice to study its effects on intact spinal cord. Then, genetically modified mice were created to invalidate the IL-1\u03b1 receptor, the IL-1R1, in cell populations specific to the spinal cord. IL-1\u03b1 was then injected in mice and the spinal cords were observed using different microscopy methods to see how cells responds in the absence of IL-1R1 in oligodendrocytes, microglia, astrocytes or endothelial cells. Along with observing the effects of IL-1\u03b1 on inflammation, cell activity and cell death in intact and injured spinal cord, studies of locomotor recovery post-SCI were performed.<\/p>\n\n\n\n
Main findings<\/h2>\n\n\n\n
IL-1\u03b1 administration to intact mice results in immune cell infiltration and spinal cord oligodendrocytes death, replicating some of the acute effects of SCI. Interestingly, dead oligodendrocytes were replaced within 3 to 5 days by new oligodendrocytes, which may be more capable of remyelination. IL-1\u03b1 or IL-1R1 invalidated mice recover more rapidly and more efficiently their locomotor function after SCI. Having demonstrated detrimental effects of IL-1\u03b1\/IL-1R1 signaling in the injured spinal cord, researchers therefore aimed to investigate the mechanism underlying inflammation and oligodendrocyte death. Using genetically modified mice, it was shown that IL-1\u03b1 effects on oligodendrocyte death are indirect. This death is partially caused by astrocytes, which are transformed into cells with toxic effects under IL-1\u03b1\u2019s influence. Indeed, these so-called toxic astrocytes release reactive chemicals called \u2018reactive oxygen species\u2019, which cause oligodendrocytes\u2019 death. It is also mediated by endothelial cells forming the spinal neurovasculature. Indeed, once stimulated by IL-1\u03b1, endothelial cells allow neutrophil infiltration and neuroinflammation. In both cases, IL-1\u03b1 receptor inactivation on the surface of astrocytes or endothelial cells greatly reduces oligodendrocytes\u2019 death.<\/p>\n\n\n\n
Take home message<\/h2>\n\n\n\n
SCI affect millions of otherwise healthy men and women\u2019s lives, often without warning. It\u2019s obviously impossible to completely prevent such accidents and the primary damage they cause. However, a better understanding of the mechanisms underlying nerve tissue loss in the hours and days following the so-called primary injury, could allow a better control of secondary damage and thus limit the loss of function. This work shows that the release of IL-1\u03b1 after SCI stimulates astrocytes and endothelial cells to adopt toxic behaviors causing inflammation and oligodendrocyte death.<\/p>\n\n\n\n
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