• Yunan Lin, Lei Lei, Ling-Sha Ju, Ning Xu, Timothy E Morey, Nikolaus Gravenstein, Jianjun Yang, and Anatoly E Martynyuk.
• Department of Anesthesiology, University of Florida College of Medicine, Gainesville, FL, United States; Department of Anesthesiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.
• Neurosci. Lett. 2020 Sep 14; 735: 135240.

BackgroundDeficiencies in neurocognitive function have been found in late childhood or adolescence in patients who had prolonged and/or repeated early-life general anesthesia. Animal studies suggest that anesthetic-induced impairment in the neuron-specific K+-2Cl- (Kcc2) Cl- exporter expression, which regulates developmental maturation of GABA type A receptor (GABAAR) signaling from excitatory to inhibitory, may play a mediating role. We tested whether the DNA methyltransferase (DNMT) inhibitor decitabine ameliorates the anesthetic's adverse effects.MethodsSprague-Dawley male rats were injected with vehicle or decitabine 30 min before 2.1 % sevoflurane exposure for 5 h on postnatal day 5 (P5). On P19, P20, or P21, electroencephalography-detectable seizures were measured during 1 h of sevoflurane exposure, followed by collection of the trunk blood and brain tissue samples. Other rats were evaluated for changes in hippocampal CA1 dendrite morphology and gene expressions on ≥ P120.ResultsRats in the vehicle plus sevoflurane group responded to sevoflurane exposure on P19, P20 or P21 with electroencephalography-detectable seizures and stress-like corticosterone secretion and had altered hippocampal dendrite morphology in adulthood. These rats had expressions of Kcc2 and Dnmt genes downregulated and upregulated, respectively, in the P19 - P21 cortex and hypothalamus and the ≥ P120 hippocampus. All measured parameters in the sevoflurane-exposed rats that were pretreated with decitabine were not different from those in the control group.ConclusionsNeonatal exposure to sevoflurane sensitizes rats to adverse effects of repeated exposure to the anesthetic. The anesthetic-caused changes in the decitabine-sensitive mechanisms may play a mediating role in the developmental effects of early-life anesthesia.Copyright © 2020. Published by Elsevier B.V.

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