Demonstrates microglia pyroptosis-driven IL-18 causes white matter injury in the developing brain, suggesting new therapeutic targets.
Hypothermia is widely acknowledged to exert protective effects against cerebral hypoxic-ischemic injury. Despite the neuroprotective effects of hypothermia, the developing brain remains vulnerable to white matter injury (WMI) during hypothermic hypoxia-ischemia, potentially disrupting neurodevelopment and leading to long-term neurological deficits. However, the mechanisms underlying WMI and effective therapeutic strategies following hypothermic hypoxia-ischemia in the developing brain are not well understood. Our study demonstrates that microglia experience pyroptosis following hypothermic hypoxia-ischemia. The release of interleukin 18 (IL-18) derived from pyroptotic microglia induces mature oligodendrocyte death and axonal demyelination, resulting in WMI. Pharmacological inhibition of pyroptosis with disulfiram (DSF) significantly alleviates WMI in vitro and in vivo . These findings highlight microglia pyroptosis as a potential therapeutic target to prevent neurodevelopmental impairment in the developing brain following hypothermic hypoxia-ischemia.
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Chen et al. (2026) studied this question.
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