title: Neonatal Repeated Exposure to Isoflurane not Sevoflurane in Mice Reversibly Impaired Spatial Cognition at Juvenile-Age.
abstract: Inhalation anesthetics facilitate surgical procedures in millions of children each year. However, animal studies demonstrate that exposure to the inhalation anesthetic isoflurane may cause neuronal cell death in developing brains. The long-term cytotoxic effects of sevoflurane, the most popular pediatric anesthetic, have not been compared with isoflurane. Thus, this study was designed to compare the effects of equipotent doses of these two anesthetics on neonatal long-term neurotoxicity. Postnatal 7-day-old (P7) C57/BL male mice were exposed to 1.5% isoflurane or 2.2% sevoflurane 2 h a day for 3 days. Non-anesthetized mice served as controls. The effects of anesthesia on learning and memory were assessed using the Morris Water Maze (MWM) at Postnatal days 30 (P30) and P60 respectively. The hippocampal content of N-methyl-D-aspartate receptor subunits (NMDA), brain-derived neurotrophic factor (BDNF), and synaptophysin (Syn) were determined by Western Blot. Neuron structure and apoptosis were assessed via Nissl and TUNEL staining, respectively. The isoflurane group exhibited cognitive impairment at P30. Repeated inhalation of isoflurane or sevoflurane caused different degrees of apoptosis and damaged hippocampal neurons in neonatal mice, particularly isoflurane. In neonatal mice, repeated exposure to isoflurane, but not sevoflurane, caused spatial cognitive impairments in juvenile mice. Our findings suggest that isoflurane induces significantly greater neurodegeneration than an equipotent minimum alveolar concentration of sevoflurane.
authors.affiliation: Department of Anesthesiology, Tongji Hospital, Tongji University, Shanghai, 200065, China. jianhuiliu_1246@163.com.
authors.forename: Jianhui
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Anesthesiology, Tongji Hospital, Tongji University, Shanghai, 200065, China.
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Anesthesiology, Tongji Hospital, Tongji University, Shanghai, 200065, China.
authors.forename: Junjun
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Anesthesiology, Tongji Hospital, Tongji University, Shanghai, 200065, China.
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Image and Radiology, Renji Hospital, Jiaotong University, Shanghai, 200127, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Image and Radiology, Tongji Hospital, Tongji University, Shanghai, 200065, China.
authors.forename: Peijun
authors.initials: P
authors.lastname: Wang
mesh_terms: D018685:Anesthetics, Inhalation / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D000831:Animals, Newborn; D003072:Cognition Disorders / Q000139:chemically induced* / Q000378:metabolism*; D007530:Isoflurane / Q000008:administration & dosage / Q000633:toxicity*; D008297:Male; D018782:Maze Learning / Q000187:drug effects* / Q000502:physiology; D008738:Methyl Ethers / Q000008:administration & dosage / Q000633:toxicity*; D051379:Mice; D008810:Mice, Inbred C57BL; D000077149:Sevoflurane
chemical_list: D018685:Anesthetics, Inhalation; D008738:Methyl Ethers; D000077149:Sevoflurane; D007530:Isoflurane
keywords: Cognitive impairment; Hippocampus; Isoflurane; Sevoflurane