蛛网膜下腔出血的发病率和死亡率较高，且缺乏有效的治疗方法。细胞焦亡是蛛网膜下腔出血后早期脑损伤的重要机制。此前的研究已证实肿瘤坏死因子刺激基因6（TSG-6）可以通过抑制氧化应激和细胞凋亡发挥神经保护作用。然而，迄今为止还没有研究探讨TSG-6是否可以减轻蛛网膜下腔出血后早期脑损伤的焦亡。本研究采用血管内穿孔法建立C57BL/6J小鼠蛛网膜下腔出血模型。我们的结果表明，TSG-6 表达主要在星形胶质细胞中检测到，此外还有 NLRC4 和gasdermin-D (GSDMD)。蛛网膜下腔出血后NLRC4、GSDMD及其N末端结构域（GSDMD-N）和cleaved caspase-1的表达显着增强，并伴有脑水肿和神经功能损害。为了探索TSG-6如何影响蛛网膜下腔出血后早期脑损伤期间的细胞焦亡，将重组人TSG-6或靶向TSG-6的siRNA注射到脑室中。外源性 TSG-6 给药下调 NLRC4 和细胞焦亡相关蛋白的表达，并减轻脑水肿和神经功能缺损。此外，TSG-6敲低进一步增加了NLRC4的表达，并伴有更严重的星形胶质细胞焦亡。总之，我们的研究表明，TSG-6 通过抑制 NLRC4 炎性体激活诱导的星形胶质细胞焦亡，为蛛网膜下腔出血后的早期脑损伤提供神经保护。

Subarachnoid hemorrhage is associated with high morbidity and mortality and lacks effective treatment. Pyroptosis is a crucial mechanism underlying early brain injury after subarachnoid hemorrhage. Previous studies have confirmed that tumor necrosis factor-stimulated gene-6 (TSG-6) can exert a neuroprotective effect by suppressing oxidative stress and apoptosis. However, no study to date has explored whether TSG-6 can alleviate pyroptosis in early brain injury after subarachnoid hemorrhage. In this study, a C57BL/6J mouse model of subarachnoid hemorrhage was established using the endovascular perforation method. Our results indicated that TSG-6 expression was predominantly detected in astrocytes, along with NLRC4 and gasdermin-D (GSDMD). The expression of NLRC4, GSDMD and its N-terminal domain (GSDMD-N), and cleaved caspase-1 was significantly enhanced after subarachnoid hemorrhage and accompanied by brain edema and neurological impairment. To explore how TSG-6 affects pyroptosis during early brain injury after subarachnoid hemorrhage, recombinant human TSG-6 or a siRNA targeting TSG-6 was injected into the cerebral ventricles. Exogenous TSG-6 administration downregulated the expression of NLRC4 and pyroptosis-associated proteins and alleviated brain edema and neurological deficits. Moreover, TSG-6 knockdown further increased the expression of NLRC4, which was accompanied by more severe astrocyte pyroptosis. In summary, our study revealed that TSG-6 provides neuroprotection against early brain injury after subarachnoid hemorrhage by suppressing NLRC4 inflammasome activation-induced astrocyte pyroptosis.