• Xianshu Ju, Yunseon Jang, Jun Young Heo, Jiho Park, Sangwon Yun, Sangil Park, Yang Hoon Huh, Hyo-Jeong Kim, Yulim Lee, Yoon Hee Kim, Chae Seong Lim, Sun Yeul Lee, Youngkwon Ko, Gi Ryang Kweon, and Woosuk Chung.
• Department of Medical Science, Chungnam National University School of Medicine, Daejeon, South Korea.
• Neurotoxicology. 2019 Jan 1; 70: 146-153.

BackgroundSex plays an important yet often underexplored role in neurodevelopment and neurotoxicity. While several studies report the importance of sex regarding anesthesia-induced neurotoxicity in neonatal mice, only few have focused on the late postnatal period. Here, to further understand the importance of sex regarding the neurobiological changes after early anesthesia during the critical synaptogenic period, we exposed postnatal day 16, 17 (PND 16, 17) mice to sevoflurane in pediatric patients and performed detailed evaluations in the hippocampus.MethodsPND 16, 17 mice received a single exposure of oxygen with or without sevoflurane (2.5%) for 2 h. Changes of the hippocampus were analyzed in male and female mice 6 h after exposure: excitatory/inhibitory synaptic transmission, protein/mRNA expression levels of excitatory/inhibitory synaptic molecules (GluR1, GluR2, PSD95, gephyrin, GAD65), and number of excitatory synapses.ResultsSevoflurane exposure increased the frequency of miniature excitatory postsynaptic currents specifically in male mice (control: 0.07 ± 0.04 [Hz]; sevoflurane: 14.72 ± 0.08 [Hz]), while miniature inhibitory postsynaptic currents were affected specifically in female mice. The protein/mRNA expression levels of excitatory synaptic molecules were also increased specifically in male mice. Unexpectedly, protein/mRNA expression levels of inhibitory synaptic molecules were increased in both sexes, and there was no male-specific increase of excitatory synapse number.ConclusionsExposure of mice to sevoflurane during the critical, late postnatal period induces sex-dependent changes in the hippocampus. Although often disregarded, our results confirm the importance of sex as a biological variable when studying the changes triggered by early anesthesia.Copyright © 2018 Elsevier B.V. All rights reserved.

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