Neonatal exposure to sevoflurane may not cause learning and memory deficits and behavioral abnormality in the childhood of Cynomolgus monkeys

Results of animal studies have raised a significant concern that commonly used general anesthetics may induce neurotoxicity in children. It may be difficult to resolve this concern with human studies because randomizing children only for testing anesthetic toxicity may not be feasible. We randomized 6-day old male Cynomolgus monkeys to receive or not to receive sevoflurane anesthesia at surgical plane for 5 h. Sevoflurane is the most commonly used general anesthetic in children in the U.S.A. Here, we showed that sevoflurane anesthesia did not affect the behavior evaluated by holding cage method when the monkeys were 3 and 7 months old. However, there was an age-dependent decrease in the frequency of stress events and environmental exploration behavior during the test. Sevoflurane also did not affect the learning and memory of the monkeys when they were assessed from the age of 7 months. Finally, sevoflurane did not affect the expression of multiple neuron-specific proteins in the hippocampus and cerebral cortex of 10-month old monkeys after all behavioral and cognitive tests were completed. These results suggest that exposure of neonatal monkey to sevoflurane may not affect cognition, behavior and neuronal structures in childhood, indicating the safety of sevoflurane anesthesia in children.