title: Single sevoflurane exposure increases methyl-CpG island binding protein 2 phosphorylation in the hippocampus of developing mice.
abstract: Sevoflurane is an inhaled anesthetic that is widely used in clinical practice, particularly for pediatric anesthesia. Previous studies have suggested that sevoflurane may induce neurotoxicity in the brains of neonatal mice. In the present study, the possible mechanism of neurodegeneration induced by sevoflurane in the developing brain, and the possibility that memantine treatment is able to reverse this phenomenon, were investigated. On postnatal day 7 (P7) C57BL/6 mice were continuously exposed to 1.5% sevoflurane for 2 h following pre-injection of saline or memantine. Methyl-CpG island binding protein 2 (MeCP2), cAMP response element-binding protein (CREB) and brain-derived neurotrophic factor (BDNF) expression in the hippocampus was measured by western blotting. Exposure to 1.5% sevoflurane resulted in increased MeCP2 phosphorylation in the hippocampus, which was reversed by memantine injection. However, neither CREB phosphorylation nor BDNF expression were significantly altered by sevoflurane treatment. The current study indicated that sevoflurane causes neurotoxicity in the developing brain, and that this may be attributed to increased MeCP2 phosphorylation in the hippocampus. It was also demonstrated that this neurotoxicity can be prevented by the N-methyl-D-aspartate glutamate receptor inhibitor memantine.
authors.affiliation: Department of Anesthesia, Zhongshan Hospital, Fudan University, Shanghai 200032, P.R. China.
authors.forename: Xiao-Dan
authors.initials: XD
authors.lastname: Han
authors.affiliation: Department of Anesthesia, Zhongshan Hospital, Fudan University, Shanghai 200032, P.R. China.
authors.forename: Min
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Anesthesia, Zhongshan Hospital, Fudan University, Shanghai 200032, P.R. China.
authors.forename: Xiao-Guang
authors.initials: XG
authors.lastname: Zhang
authors.affiliation: Department of Anesthesia, Zhongshan Hospital, Fudan University, Shanghai 200032, P.R. China.
authors.forename: Zhang-Gang
authors.initials: ZG
authors.lastname: Xue
authors.affiliation: Department of Anesthesia, Zhongshan Hospital, Fudan University, Shanghai 200032, P.R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Cang
mesh_terms: D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D001784:Blood Gas Analysis; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D008559:Memantine / Q000494:pharmacology; D008738:Methyl Ethers / Q000494:pharmacology*; D051783:Methyl-CpG-Binding Protein 2 / Q000378:metabolism*; D051379:Mice; D010766:Phosphorylation / Q000187:drug effects; D000077149:Sevoflurane
chemical_list: D018685:Anesthetics, Inhalation; D019208:Brain-Derived Neurotrophic Factor; D017362:Cyclic AMP Response Element-Binding Protein; D008738:Methyl Ethers; D051783:Methyl-CpG-Binding Protein 2; D000077149:Sevoflurane; D008559:Memantine