title: Sevoflurane decreases self-renewal capacity and causes c-Jun N-terminal kinase-mediated damage of rat fetal neural stem cells.
abstract: Increasing studies have demonstrated that sevoflurane can induce neurotoxicity in the developing brains. JNK normally promotes apoptosis. It was hypothesized that sevoflurane affected the proliferation and differentiation of FNSCs and induced cell apoptosis, which caused the learning and memory deficits via JNK pathway. Sevoflurane at a concentration of 1.2% did not induce damage on the FNSCS. However, concentrations of 2.4% and 4.8% decreased the cell viability, as shown by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and increased apoptosis, as shown by flow cytometry. The 5-ethynyl-2'-deoxyuridine (EdU) incorporation assay demonstrated that 4.8% sevoflurane reduced the proliferation of FNSCs. Compared with the control group, the 4.8% sevoflurane group showed a decrease in the proportion of undifferentiated FNSCs at 6-h exposure; 4.8% sevoflurane could increase the p-JNK/JNK ratio. JNK inhibition by the specific inhibitor SP600125 enhanced partially the cell viability. Cumulatively, 4.8% sevoflurane induced significant damage on FNSCs; it decreased cell proliferation and proportion of undifferentiated cells as well. JNK pathway might play a key role in the decrease in survival of FNSCs induced by an inhaled anesthetic. The present findings might raise the possibility that JNK inhibition has therapeutic potential in protecting FNSCs from the adverse effects of the inhaled anesthetic.
authors.affiliation: Department of Anesthesiology, International Peace Maternity and Child Health Hospital, Shanghai Jiao Tong University School of Medicine, 200030, Shanghai, China.
authors.forename: Zeyong
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Wannan Medical College, Wuhu, 241000, Anhui, China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Lv
authors.affiliation: Department of Anesthesiology, First Affiliated Hospital of AnHui Medical University, Hefei, 230022, Anhui, China.
authors.forename: Xingxing
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Anesthesiology, International Peace Maternity and Child Health Hospital, Shanghai Jiao Tong University School of Medicine, 200030, Shanghai, China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Meng
authors.affiliation: Department of Anesthesiology, International Peace Maternity and Child Health Hospital, Shanghai Jiao Tong University School of Medicine, 200030, Shanghai, China.
authors.forename: Qiling
authors.initials: Q
authors.lastname: Yang
authors.affiliation: Department of Anesthesiology, International Peace Maternity and Child Health Hospital, Shanghai Jiao Tong University School of Medicine, 200030, Shanghai, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Ma
authors.affiliation: Department of Anesthesiology, First Affiliated Hospital of AnHui Medical University, Hefei, 230022, Anhui, China.
authors.forename: Yuanhai
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Biochemistry, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
authors.forename: Zun Ji
authors.initials: ZJ
authors.lastname: Ke
mesh_terms: D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D000066673:Cell Self Renewal / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008738:Methyl Ethers / Q000494:pharmacology*; D057054:Molecular Imaging; D058953:Neural Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D000077149:Sevoflurane
chemical_list: D018685:Anesthetics, Inhalation; D008738:Methyl Ethers; D000077149:Sevoflurane; D048031:JNK Mitogen-Activated Protein Kinases