Abstract

Septic encephalopathy (SE) is a devastating consequence of sepsis, a hyper-triggered host response against infectious challenge, which ultimately leads to brain damage. The present study examined whether sevoflurane (SVF), a volatile anaesthetic, can counteract the perturbation of homeostasis in a caecal ligation and puncture (CLP)-induced mouse model of SE. SVF enhances neurocognition in terms of spatial memory improvement via counter-regulation of activated oxidative-inflammatory stress and pyroptotic processes in SE. Further, the beneficial effects of SVF against SE are mediated by activation of silent information regulator 1 (SIRT1)-mediated reduction of reactive oxygen species (ROS) level, regulation of thioredoxin (TXN) and thioredoxin interacting protein (TIP) levels, reduction of inflammatory-pyroptotic signalling (NLRP3, caspase 1/11, GSDMD, TLR4 and TRIF) proteins, as well as a reduction of inflammatory cytokine (IL-1β and IL-18) levels. These findings suggest that SVF may have therapeutic potential for the treatment of SE and associated cognitive malfunction.

摘要

脓毒性脑病 (SE) 是败血症的毁灭性后果，这是一种对感染性挑战的超触发宿主反应，最终导致脑损伤。本研究检查了七氟醚 (SVF)，一种挥发性麻醉剂，是否可以抵消盲肠结扎和穿刺 (CLP) 诱导的 SE 小鼠模型中稳态的扰动。SVF 在空间记忆改善方面通过以下方式增强神经认知SE中激活的氧化炎症应激和细胞焦亡过程的反调节。此外，SVF 对 SE 的有益作用是通过激活沉默信息调节因子 1 (SIRT1) 介导的活性氧 (ROS) 水平的降低、硫氧还蛋白 (TXN) 和硫氧还蛋白相互作用蛋白 (TIP) 水平的调节、炎性焦亡信号（NLRP3、caspase 1/11、GSDMD、TLR4 和 TRIF）蛋白，以及炎性细胞因子（IL-1β 和 IL-18）水平的降低。这些发现表明，SVF 可能具有治疗 SE 和相关认知功能障碍的治疗潜力。