Neuroinflammation is intimately associated with poor prognosis in patients with subarachnoid hemorrhage (SAH). Alpha-lipoic acid (ALA), a disulfide antioxidant, has been shown to be neuroprotective in an in vivo model of neurological injury; however, the role of ALA in SAH has never been evaluated. In this study, the Sprague-Dawley rats SAH model was induced by endovascular perforation method. ALA was transplanted intravenously into rats, and SR-717, a stimulator of interferon genes (STING) agonist, was injected intraperitoneally. The effects of ALA on early brain injury were assayed by neurological score, hematoxylin and eosin staining and Nissl staining. Immunohistochemistry staining and Western blotting were used to analyze various proteins. ALA significantly reduced STING- NLRP3 protein expression and decreased cell death, which in turn mitigated the neurobehavioral dysfunction following SAH. Furthermore, coadministration of ALA and SR-717 promoted STING-NLRP3 signaling pathway activation following SAH, which reversed the inhibitory effect of ALA on STING-NLRP3 protein activation and increased the neurological deficits. In conclusion, ALA may be a promising therapeutic strategy for alleviating early brain injury after SAH.

中文翻译：

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α-硫辛酸 (ALA) 通过抑制 STING-NLRP3 炎症信号传导，改善 Sprague-Dawley (SD) 大鼠蛛网膜下腔出血后的早期脑损伤。

神经炎症与蛛网膜下腔出血（SAH）患者的不良预后密切相关。 α-硫辛酸 (ALA) 是一种二硫化物抗氧化剂，在神经损伤的体内模型中已被证明具有神经保护作用；然而，ALA 在 SAH 中的作用从未得到评估。本研究采用血管内穿孔法制备Sprague-Dawley大鼠蛛网膜下腔出血模型。将ALA静脉移植到大鼠体内，并腹腔注射干扰素基因刺激剂（STING）激动剂SR-717。通过神经评分、苏木精-伊红染色和尼氏染色测定ALA对早期脑损伤的影响。使用免疫组织化学染色和蛋白质印迹分析各种蛋白质。 ALA 显着降低 STING-NLRP3 蛋白表达并减少细胞死亡，从而减轻 SAH 后的神经行为功能障碍。此外，ALA和SR-717的共同给药促进了SAH后STING-NLRP3信号通路的激活，从而逆转了ALA对STING-NLRP3蛋白激活的抑制作用并增加了神经功能缺损。总之，ALA 可能是减轻 SAH 后早期脑损伤的一种有前景的治疗策略。