Sevoflurane enhanced the clearance of Aβ1-40 in hippocampus under surgery via up-regulating AQP-4 expression in astrocyte.

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.