LAUSR

Neuronal cell death is considered the symbol of early brain injury after subarachnoid hemorrhage (SAH), but the mechanism was still unclear. DDX3X, a member of the DEAD-box helicase family, has a major effect on immune inflammation by mediating RNA metabolism. Recent studies report that DDX3X regulates the balance of NLRP3 inflammasome and stress granules in stress conditions, but the role of DDX3X in SAH is still unknown. Therefore, we conducted in vivo and in vitro experiments to investigate the role and mechanism of DDX3X in SAH. Western blot and immunofluorescence showed that SAH promoted DDX3X expression, especially in the cortical neurons. After upregulation of DDX3X, the NLRP3 inflammasome was activated and autophagy was inhibited, resulting in neurological dysfunction and damage to the blood–brain barrier. Further rescue experiments confirmed that DDX3X aggravated neuronal pyroptosis and inhibited autophagy via the NLRP3 inflammasome after SAH. Hence, DDX3X might be a potential therapeutic target for early brain injury of SAH. After SAH, DDX3X was activated in both in vivo and in vivo neurons. DDX3X aggravated neuronal pyroptosis and inhibited autophagy via NLRP3 inflammasome.