DDX3X aggravates neuronal pyroptosis and inhibits autophagy via NLRP3 inflammasome after experimental subarachnoid hemorrhage

Neuronal cell death was considered as the symbol of early brain injury after subarachnoid hemorrhage (SAH), but the mechanism was still unclear. DDX3X, a member of DEAD-box helicase family, has a major effect on many biological processes, such as immune inflammation, growth and development, by mediating RNA metabolism. Recent study reported that DDX3X regulated the balance of NLRP3 inflammasome and stress granules in stress condition, but the role of DDX3X in SAH was still unknown. Therefore, we conduced the in-vivo and in-vitro experiments for the role and mechanism of DDX3X in SAH. Western blot and immunofluorescence showed that SAH promoted DDX3X expression, especially in the cortical neurons. After up-regulation of DDX3X, NLRP3 inflammasome was activated and autophagy was inhibited, resulting in the neurological dysfunction and damage of blood brain barrier. Further rescue experiments confirmed that DDX3X aggravated neuronal pyroptosis and inhibited autophagy via NLRP3 inflammasome after SAH. Hence, DDX3X might be a potential therapeutic target for early brain injury of SAH.