Effects of multiple exposures to sevoflurane at sub-MAC doses on neuroapoptosis and cognitive function during the neonatal period

Abstract

IntroductionRecent studies have suggested that children who are exposed multiple times to anesthesia have an increased risk of neurocognitive impairment. ObjectiveTo analyze at a histological level the neurodegenerative, cognitive and behavioral effects following repeated exposures to sevoflurane at doses below the minimum alveolar concentration in neonatal rats. MethodsWistar rats were exposed to 2.3% sevoflurane, one, two or three times for 1h, in the course of 5–7 days, with 24-h intervals between each exposure. The neuroapoptotic effect of the anesthetic agent was subsequently determined using immunohistochemical labeling with caspase-3, Fox-3 and CD95. Learning was assessed with the Morris Water Maze, and the anxiety-related behavior was assessed with the Elevated Plus-Maze. ResultsEvery experimental group showed evidence of neuronal apoptosis measured with caspase-3; however, the apoptosis was more evident in the sevoflurane group and in the first exposure groups. The total time spent in the open arms of the Elevated Plus-Maze (t test p=0.113) was not statistically significant as compared to the control group. When comparing the test time vs. the control group, the Morris Water Maze showed a statistically significant difference (t test p<0.001). ConclusionsSevoflurane exposure of neonatal rats for short and repeated time intervals induces neuronal death probably due to apoptosis, through caspase-3 activation. This results in learning deficit, particularly in terms of spatial memory acquisition.