小胶质细胞热解衍生的IL-18驱动低温缺氧缺血后发育中脑白质损伤，这一成果由上海交通大学医学院祝忠群小组经过不懈努力而取得。该研究于2026年3月9日发表于国际一流学术期刊《神经科学通报》杂志上。

低温对脑缺氧缺血性损伤具有保护作用。尽管低温具有神经保护作用，但在低温缺氧缺血过程中，发育中的大脑仍然容易受到白质损伤（WMI）的伤害，这可能会破坏神经发育并导致长期的神经功能缺损。

然而，WMI的机制和发育中的大脑低温缺氧缺血后的有效治疗策略尚不清楚。他们的研究表明，小胶质细胞在低温缺氧缺血后经历焦亡。来自焦性小胶质细胞的白介素18（IL-18）的释放诱导成熟少突胶质细胞死亡和轴突脱髓鞘，导致WMI。双硫仑（DSF）对焦亡的药理抑制可显著减轻体内外WMI。这些发现强调了小胶质细胞焦亡作为一个潜在的治疗靶点，以防止低低温缺氧缺血后发育中的大脑神经发育障碍。

附：英文原文

Title: Microglia Pyroptosis-Derived IL-18 Drives White Matter Injury in Developing Brain following Hypothermic Hypoxia-Ischemia

Author: Chen, Hongtong, Jin, Shengyu, Liu, Mingdong, Zhu, Yifan, Zhang, Liren, Li, Cong, Liu, Peng, Tong, Xiaoping, Zhu, Zhongqun

Issue&Volume: 2026-03-09

Abstract: 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.

DOI: 10.1007/s12264-026-01602-9

Source: https://link.springer.com/article/10.1007/s12264-026-01602-9