Background and Aims: Cognitive impairment is one of the major complications of subarachnoid hemorrhage (SAH) and is closely associated with neuroinflammation. Hydrogen sulfide (H₂S) has been shown to have an anti-inflammatory effect and reduce cognitive impairment in neurodegenerative diseases, but its effects in SAH have been little studied. This study aimed to investigate the effects of H₂S on cognitive impairment after SAH and the possible underlying mechanisms.

Methods: Forty-eight male Sprague–Dawley (SD) rats were randomly divided into three groups: a sham group, a SAH group, and a SAH + NaHS (an H₂S donor) group. The endovascular perforation technique was used to establish the experimental SAH model. NaHS was administered intraperitoneally. An active avoidance test (AAT) was performed to investigate cognitive function. The expression of TNF-α, toll-like receptor 4 (TLR4), and NF-κB p65 in the hippocampus was measured by Western blot and immunohistochemistry. The types of cells expressing TNF-α were detected by double immunofluorescence staining.

Results: Compared to that in the sham group, the learning and memory ability of rats in the SAH group was damaged. Furthermore, the expression of TNF-α, TLR4, and NF-κB p65 in the hippocampus was elevated in the SAH group (p < 0.05). TNF-α was mainly expressed in activated microglia, which was consistent with the expression of TLR4. Treatment with NaHS significantly decreased the cognitive impairment of rats after SAH and simultaneously reduced the expression of TNF-α, TLR4, and NF-κB p65 and alleviated the nuclear translocation of NF-κB p65 (p < 0.05).

Conclusions: The neuroinflammation reaction in microglia contributes to cognitive impairment after SAH. H₂S reduced the cognitive impairment of rats after SAH by ameliorating neuroinflammation in microglia, potentially via the TLR4/NF-κB pathway.

背景和目标：认知障碍是蛛网膜下腔出血（SAH）的主要并发症之一，与神经炎症密切相关。硫化氢（H ₂ S）已被证明具有抗炎作用并减少神经退行性疾病中的认知障碍，但对其在SAH中的作用尚未进行研究。本研究旨在探讨H ₂ S对SAH后认知障碍的影响及其可能的潜在机制。

方法：将48只雄性Sprague-Dawley（SD）大鼠随机分为三组：假手术组，SAH组和SAH + NaHS（H ₂ S供体）组。采用血管内穿孔技术建立实验性SAH模型。NaHS腹膜内给药。进行主动回避测试（AAT）以研究认知功能。用Western blot和免疫组织化学方法检测海马中TNF-α，toll​​样受体4（TLR4）和NF-κBp65的表达。通过双重免疫荧光染色检测表达TNF-α的细胞类型。

结果：与假手术组相比，SAH组大鼠的学习记忆能力受到损害。此外，SAH组海马中TNF-α，TLR4和NF-κBp65的表达升高（p<0.05）。TNF-α主要在活化的小胶质细胞中表达，与TLR4的表达一致。NaHS处理可显着降低SAH后大鼠的认知障碍，同时降低TNF-α，TLR4和NF-κBp65的表达并减轻NF-κBp65的核易位（p <0.05）。

结论：小胶质细胞的神经炎症反应有助于SAH后的认知障碍。H ₂ S可通过改善小胶质细胞的神经炎症减轻SAH大鼠的认知障碍通过 TLR4 /NF-κB途径。