Effects of multiple exposures to sevoflurane at sub-MAC doses on neuroapoptosis and cognitive function during the neonatal period
Abstract
Introduction: Recent studies have suggested that children who are exposed multiple times to anesthesia have an increased risk of neurocognitive impairment.
Objective: To 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.
Methods: Wistar rats were exposed to 2.3% sevoflurane, one, two or three times for 1 h, 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.
Results: Every experimental group showed evidence of neuronal apoptosis measured withcaspase-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).
Conclusions: Sevoflurane exposure of neonate 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.
References
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