Li Hui, Hu Wen, Wu Zhen, Tian Bin, Ren Yimin, Zou Xiaohua
College of Anesthesia, Guizhou Medical University, Guizhou Province, Guiyang 550004, China; Department of Anesthesiology, The Affiliated Hospital of Guizhou Medical University, Guizhou Province, Guiyang 550004, China; Guizhou Medical University Key Laboratory of Anesthesia and Pain Mechanism Research, Guizhou Province, Guiyang, 550004, China.
College of Anesthesia, Guizhou Medical University, Guizhou Province, Guiyang 550004, China; Guizhou Medical University Key Laboratory of Anesthesia and Pain Mechanism Research, Guizhou Province, Guiyang, 550004, China.
Eur J Pharmacol. 2024 Nov 15;983:177014. doi: 10.1016/j.ejphar.2024.177014. Epub 2024 Sep 21.
Microglia-mediated neuroinflammation is critical in the pathogenesis of sepsis-associated encephalopathy(SAE). Identifying the key factors that inhibit microglia-mediated neuroinflammation holds promise as a potential target for preventing and treating SAE. Esketamine, a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist, has been proposed to possess protective and therapeutic properties against neuroinflammatory disorders. This study provides evidence that the administration of Esketamine in SAE mice improves cognitive impairments and alleviates neuronal damage by inhibiting the microglia-mediated neuroinflammation. The BDNF receptor antagonist K252a was employed in both vivo and in vitro experiments. The findings indicate that K252a successfully counteracted the beneficial effects of Esketamine on microglia and cognitive behavior in mice with SAE. Consequently, these results suggest that Esketamine inhibits microglia-mediated neuroinflammation by activating the BDNF pathway, and mitigating neuronal damage and cognitive dysfunction associated with SAE.
小胶质细胞介导的神经炎症在脓毒症相关性脑病（SAE）的发病机制中起关键作用。识别抑制小胶质细胞介导的神经炎症的关键因素有望成为预防和治疗SAE的潜在靶点。艾司氯胺酮是一种非竞争性N-甲基-D-天冬氨酸（NMDA）受体拮抗剂，已被提出具有抗神经炎症性疾病的保护和治疗特性。本研究提供的证据表明，在SAE小鼠中给予艾司氯胺酮可通过抑制小胶质细胞介导的神经炎症改善认知障碍并减轻神经元损伤。BDNF受体拮抗剂K252a用于体内和体外实验。研究结果表明，K252a成功抵消了艾司氯胺酮对SAE小鼠小胶质细胞和认知行为的有益作用。因此，这些结果表明，艾司氯胺酮通过激活BDNF通路抑制小胶质细胞介导的神经炎症，并减轻与SAE相关的神经元损伤和认知功能障碍。
