Department of Anesthesiology, Zhongshan Hospital, Fudan University, 180 Fenglin Rd, Shanghai 200032, China.
State Key Laboratory of Medical Neurobiology, School of Basic Medical Sciences and Institutes of Brain Science, Fudan University, China.
Life Sci. 2019 Mar 15;221:143-151. doi: 10.1016/j.lfs.2019.02.024. Epub 2019 Feb 11.
The neurotoxicity of anesthetics on developing brain has been a focused issue for years. However, controversy exists between human and animal studies and surgery may be a potential reason for this. The discovery of glymphatic system, a pathway eliminating soluble substance from central nervous system (CNS), together with recent evidence that surgery-induced Aβ increase contributes to cognition dysfunction made us rethink about the influence of anesthetics on cognitive function. The function of glymphatic system was proved to be enhanced by sleep and sedation, so we assumed that under clinical situation Aβ1-40 whose accumulation played important role in cognitive dysfunction was increased by surgery and eliminated from CNS by glymphatic system. The function of glymphatic system is facilitated by aquaporin-4 (AQP-4), a water channel expressed in highly polarized manor in astrocytic endfeet, whose transcription is regulated by nuclear factor of activated T cells 5 (NFAT5). Our results suggest that under brief operation and sevoflurane exposure, surgery may be the main cause of Aβ increase and sevoflurane increase the elimination of Aβ by up-regulating AQP-4 which is the key component in glymphatic system.
麻醉药对发育中大脑的神经毒性一直是多年来的研究焦点。然而，人类和动物研究之间存在争议，手术可能是造成这种争议的一个潜在原因。最近发现了一种称为“脑淋巴系统”的途径，它可以清除中枢神经系统（CNS）中的可溶性物质，并且有证据表明手术引起的 Aβ增加会导致认知功能障碍，这使我们重新思考麻醉药对认知功能的影响。脑淋巴系统的功能已被证明可以通过睡眠和镇静来增强，因此我们假设在临床情况下，在认知功能障碍中起重要作用的 Aβ1-40 会因手术而增加，并通过脑淋巴系统从 CNS 中清除。脑淋巴系统的功能由水通道蛋白-4（AQP-4）促进，AQP-4 在星形胶质细胞终足中以高度极化的方式表达，其转录受活化 T 细胞核因子 5（NFAT5）调节。我们的研究结果表明，在短暂的手术和七氟醚暴露下，手术可能是 Aβ增加的主要原因，而七氟醚通过上调 AQP-4 增加 Aβ的清除，AQP-4 是脑淋巴系统的关键组成部分。
