Abstract
Sevoflurane, the most widely used anesthetic in clinical practice, has been shown to induce apoptosis, inhibit neurogenesis, and cause learning and memory impairment in young mice. However, the underlying mechanism is still unknown. In this study, wild-type and the FAS- or FAS ligand (FASL)-knockout mice (age 7 days) were exposed to sevoflurane or pure oxygen. Western blotting was used to examine the expression of FAS protein. Terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) and bromodeoxyuridine (BrdU) staining were employed to quantify the apoptotic cells and newborn cells in the hippocampus and Morris water maze (MWM) in order to evaluate learning and memory status. Sevoflurane significantly increased the expression of FAS protein in wild-type mice. Compared to FAS- and FASL-knockout mice treated with sevoflurane, sevoflurane-treated wild-type mice exhibited more TUNEL-positive hippocampal cells and less BrdU-positive hippocampal cells. The MWM showed that compared with FAS- and FASL-knockout mice treated with sevoflurane, sevoflurane treatment of wild-type mice significantly prolonged the escape latency and reduced platform crossing times. These data suggest that sevoflurane induces neurotoxicity in young mice through FAS-FASL signaling.