title: Sevoflurane induces neurotoxicity in young mice through FAS/FASL signaling.
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.
authors.affiliation: Department of Anesthesiology, Zhengzhou Central Hospital, Zhengzhou, Henan Province, China.
authors.forename: Q
authors.initials: Q
authors.lastname: Song
authors.affiliation: Department of Anesthesiology, Zhengzhou Central Hospital, Zhengzhou, Henan Province, China.
authors.forename: Y L
authors.initials: YL
authors.lastname: Ma
authors.affiliation: Department of Anesthesiology, Zhengzhou Central Hospital, Zhengzhou, Henan Province, China.
authors.forename: J Q
authors.initials: JQ
authors.lastname: Song
authors.affiliation: Department of Anesthesiology, Zhengzhou Central Hospital, Zhengzhou, Henan Province, China.
authors.forename: Q
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Department of Anesthesiology, Zhengzhou Central Hospital, Zhengzhou, Henan Province, China.
authors.forename: G S
authors.initials: GS
authors.lastname: Xia
authors.affiliation: Department of Anesthesiology, Zhengzhou Central Hospital, Zhengzhou, Henan Province, China.
authors.forename: J Y
authors.initials: JY
authors.lastname: Ma
authors.affiliation: Department of Anesthesiology, Zhengzhou Central Hospital, Zhengzhou, Henan Province, China.
authors.forename: F
authors.initials: F
authors.lastname: Feng
authors.affiliation: Department of Anesthesia and Critical Care, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA.|Department of Hospital Infections, Shuguang Hospital Affiliated with Shanghai University of Traditional Chinese Medicine, Shanghai, China.
authors.forename: X J
authors.initials: XJ
authors.lastname: Fei
authors.affiliation: Department of Anesthesiology, Zhengzhou Central Hospital, Zhengzhou, Henan Province, China.
authors.forename: Q M
authors.initials: QM
authors.lastname: Wang
mesh_terms: D000777:Anesthetics / Q000009:adverse effects; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D053222:Fas Ligand Protein / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D018782:Maze Learning / Q000187:drug effects; D008738:Methyl Ethers / Q000009:adverse effects*; D051379:Mice; D018345:Mice, Knockout; D055495:Neurogenesis / Q000187:drug effects; D020258:Neurotoxicity Syndromes / Q000209:etiology / Q000235:genetics*; D000077149:Sevoflurane; D019014:fas Receptor / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D000777:Anesthetics; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008738:Methyl Ethers; D019014:fas Receptor; D000077149:Sevoflurane