title: Early life exposure to sevoflurane impairs adulthood spatial memory in the rat.
abstract: Sevoflurane is a general anesthetic commonly used in the pediatric setting because it is sweet-smelling, nonflammable, fast acting and has a very short recovery time. Although recent clinical data suggest that early anesthesia exposure is associated with subsequent learning and memory problems, it is difficult to determine the exact scope of developmental neurotoxicity associated with exposure to specific anesthetics such as sevoflurane. This is largely due to inconsistencies in the literature. Thus, in the present studies we evaluated the effect of early life exposure to sevoflurane (1%, 2%, 3% or 4%) on adulthood memory impairment in Sprague-Dawley rats. Animals were exposed to different regimens of sevoflurane anesthesia on postnatal days (PNDs) 3, 7, or 14 or at 7 weeks (P7W) of age and spatial memory performance was assessed in adulthood using the Morris Water Maze (MWM). Rats exposed to sevoflurane exhibited significant memory impairment which was concentration and exposure duration dependent. Disruption of MWM performance was more severe in animals exposed on both PNDs 3 and 7 than in animals exposed on both PNDs 3 and 14. The younger the animal's age at the time of exposure, the more significant the effect on later MWM performance. Compared to the neonates, animals exposed at P7W were relatively insensitive to sevoflurane: memory was impaired in this group only after repeated exposures to low doses or single exposures to high doses. Early life exposure to sevoflurane can result in spatial memory impairments in adulthood and the shorter the interval between exposures, the greater the deficit.
authors.affiliation: State Key Laboratory of Reproductive Medicine, Department of Anesthesiology and Critical Care Medicine, Nanjing Maternity and Child Health Care Hospital, Nanjing Medical University, Nanjing, Jiangsu 210004, China.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Shen
authors.forename: Yusheng
authors.initials: Y
authors.lastname: Liu
authors.forename: Shiqin
authors.initials: S
authors.lastname: Xu
authors.forename: Qingsong
authors.initials: Q
authors.lastname: Zhao
authors.forename: Xirong
authors.initials: X
authors.lastname: Guo
authors.forename: Rong
authors.initials: R
authors.lastname: Shen
authors.forename: Fuzhou
authors.initials: F
authors.lastname: Wang
mesh_terms: D000367:Age Factors; D000704:Analysis of Variance; D018685:Anesthetics, Inhalation / Q000633:toxicity*; D000818:Animals; D000831:Animals, Newborn; D002658:Developmental Disabilities / Q000139:chemically induced* / Q000150:complications; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000139:chemically induced*; D008738:Methyl Ethers / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects; D000077149:Sevoflurane; D013028:Space Perception / Q000187:drug effects*; D016019:Survival Analysis
chemical_list: D018685:Anesthetics, Inhalation; D008738:Methyl Ethers; D000077149:Sevoflurane
keywords: AUC; BID; Inhalation anesthesia; MAC; MWM; Memory; Morris Water Maze; Neonate; Neuronal toxicity; P14D; P3D; P7D; P7W; Pediatrics; SEM; SID; Sevoflurane; TID; area under curve; minimum alveolar concentration; once a day; postnatal 14 days; postnatal 3 days; postnatal 7 days; postnatal 7 weeks; standard deviation; three times a day; twice a day