Early life exposure to sevoflurane impairs adulthood spatial memory in the rat

• Published in: Neurotoxicology (Park Forest South) 2013-12, Vol.39, p.45-56
• Main Authors: Shen, Xiaofeng, Liu, Yusheng, Xu, Shiqin, Zhao, Qingsong, Guo, Xirong, Shen, Rong, Wang, Fuzhou
• Format: Article
• Language: English
• Subjects: Age Factors; Analysis of Variance; Anesthetics, Inhalation - toxicity; Animals; Animals, Newborn; Biological and medical sciences; Developmental Disabilities - chemically induced; Developmental Disabilities - complications; Disease Progression; Dose-Response Relationship, Drug; Drug Administration Schedule; General aspects; Inhalation anesthesia; Maze Learning - drug effects; Medical sciences; Memory; Memory Disorders - chemically induced; Methyl Ethers - toxicity; Neonate; Neuronal toxicity; Pediatrics; Rats; Rats, Sprague-Dawley; Reaction Time - drug effects; Sevoflurane; Space Perception - drug effects; Survival Analysis; Toxicology
• ISSN: 0161-813X; 1872-9711
• DOI: 10.1016/j.neuro.2013.08.007

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.