增强的神经炎症是围手术期神经认知障碍的重要机制。调节性T细胞（Tregs）在调节全身免疫反应方面起着关键作用。本研究旨在调查Tregs在术后认知功能障碍（POCD）的发展中的参与作用。将18个月大的老鼠进行胫骨内固定术，诱导手术相关的神经认知障碍。使用Morris水迷宫检查小鼠的认知功能。收集脾脏Tregs进行RNA测序和流式细胞术。通过酶联免疫吸附法测量循环和海马区的炎症因子水平。通过免疫荧光法检测紧密连接蛋白的存在。 胫骨内固定手术诱导老年小鼠的认知障碍，伴随着循环炎症因子水平的升高和循环Tregs的增加。从年轻小鼠中输注Tregs部分恢复了老年小鼠的血脑屏障结构并缓解了POCD。与年轻Tregs相比，老年Tregs中的差异表达基因在肿瘤坏死因子（TNF）信号途径和细胞因子-细胞因子受体互作中富集。流式细胞术表明，老年Tregs在基础和刺激条件下的功能受到抑制。CD25表位阻断保护了血脑屏障结构，降低了海马区的TNF-α水平，并改善了老年小鼠的手术相关认知功能。 阻断外周调节性T细胞可以改善老年小鼠的手术诱发认知功能，因此老年Tregs在POCD的发生中起着重要作用。©2023年。作者（们）发表。

Enhanced neuroinflammation is an important mechanism underlying perioperative neurocognitive disorders. Regulatory T cells (Tregs) play a crucial role in regulating systemic immune responses. The present study was aimed to investigate the participation of Tregs in the development of postoperative cognitive dysfunction (POCD).Surgery-associated neurocognitive disorder was induced in 18-month-old mice subjected to internal fixation of tibial fracture. Morris water maze was used to examine mice cognitive function. Splenic Tregs were collected for RNA sequencing and flow cytometry. Levels of inflammatory factors in the circulation and hippocampus were measured by enzyme-linked immunosorbent assay. Protein presences of tight junction proteins were detected by immunofluorescence.Surgery of internal fixation of tibial fracture induced cognitive impairment in aged mice, accompanied by elevated plasma levels of inflammatory factors and increased circulating Tregs. Transfusion of Tregs from young mice partially restored the structure of the blood-brain barrier and alleviated POCD in aged mice. Compared with young Tregs, differentially expressed genes in aged Tregs were enriched in tumor necrosis factor (TNF) signaling pathway and cytokine-cytokine receptor interaction. Flow cytometry revealed that aged Tregs had blunted functions under basal and stimulated conditions. Blockade of the CD25 epitope protected the blood-brain barrier structure, reduced TNF-α levels in the hippocampus, and improved surgery-associated cognition in aged mice.Blocking peripheral regulatory T cells improves surgery-induced cognitive function in aged mice. Therefore, aged Tregs play an essential role in the occurrence of POCD.© 2023. The Author(s).