The role of microglia mediated pyroptosis in neonatal hypoxic-ischemic brain damage
The role of microglia mediated pyroptosis in neonatal hypoxic-ischemic brain damage
复制标题
小胶质细胞介导的细胞焦亡在新生儿缺氧缺血性脑损伤中的作用。
DOI：
10.1016/j.bbrc.2019.11.003
复制
发表时间：
2020-01-22
影响因子：
3.1
通讯作者：
Feng, Xing
中科院分区：
文献类型：
--
作者：
Lv, Yuan;Sun, Bin;Feng, Xing
新生儿缺氧缺血性脑病(HIE)常导致新生儿死亡或严重的、不可逆转的神经功能障碍。病理上，大量细胞死亡和随后的炎症的发生表明，炎症相关的程序性细胞死亡的炎性下垂可能在HIE中起作用。在这里，通过检测HIE患者下垂途径中关键分子的变化，我们发现它们的升高水平与HIE的严重程度密切相关。接下来，我们证明了应用MCC950，一种抑制NLRP3炎症小体从而抑制下垂的小分子，显著减轻了新生大鼠缺氧缺血性脑损伤(HIBD)的下垂和损伤严重程度。从机制上，我们证明了NLRP-3/caspase-1/GSDMD轴是小胶质细胞松弛和激活所必需的。我们的数据表明小胶质细胞介导的下垂在新生儿HIE中起着关键作用，这为针对下垂的干预途径的发展提供了线索，以治疗HIE和创伤性脑损伤。(C)2019 Elsevier Inc.保留所有权利。
Neonatal hypoxic-ischemic encephalopathy (HIE) often leads to neonatal death or severe, irreversible neurological deficits. Pathologically, the occurrence of massive cell death and subsequent inflammation suggested that pyroptosis, an inflammation associated programed cell death, might play a role in HIE. Here, by measuring changes of key molecules in pyroptosis pathway in HIE patients, we discovered that their elevation levels tightly correlate with the severity of HIE. Next, we demonstrated that application of MCC950, a small molecule to inhibit NLRP3 inflammasome and thus pyroptosis, substantially alleviated pyroptosis and the injury severity in rats with neonatal hypoxic-ischemic brain damage (HIBD). Mechanistically, we showed that NLRP-3/caspase-1/GSDMD axis is required for microglia pyroptosis and activation. Our data demonstrated that microglia mediated pyroptosis played a crucial role in neonatal HIE, which shed lights into the development of intervention avenues targeting pyroptosis to treat HIE and traumatic brain injuries. (C) 2019 Elsevier Inc. All rights reserved.