Effects of Sevoflurane Exposure During Late Pregnancy on Brain Development and Beneficial Effects of Enriched Environmen
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ORIGINAL RESEARCH
Effects of Sevoflurane Exposure During Late Pregnancy on Brain Development and Beneficial Effects of Enriched Environment on Offspring Cognition Zhiqiang Yu1,2 · Jianbo Wang2 · Haiyun Wang1 · Jinxin Wang1 · Jian Cui2 · Pei Junzhang2 Received: 15 September 2019 / Accepted: 21 February 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Sevoflurane is a widely used obstetric general anesthetic, but the neurotoxic effects of late-pregnancy exposure to one minimum alveolar concentration ([MAC], 2.5%) of sevoflurane on offspring remain unclear. We investigated whether exposure to 2.5% sevoflurane during late pregnancy would affect offspring hippocampal neuronal development and neurocognitive function. On gestational day 18 (G18), rats were randomly treated with 2.5% sevoflurane in 50% oxygen for 1 (Sev × 1), 3 (Sev × 3), or 6 h (Sev × 6). The neuronal apoptosis rate and mature brain-derived neurotrophic factor (mBDNF) and postsynaptic density protein 95 (PSD-95) expression levels were measured in offspring hippocampi on postnatal day 1 (P1) and P35. Dendritic spine formation and cognitive function were examined on P35. The neuronal apoptosis rate was enhanced, and mBDNF and PSD-95 levels were reduced in the Sev × 3 and Sev × 6 groups on P1. mBDNF and PSD-95 levels were also decreased in the Sev × 6 group on P35. The error rate was elevated in the maze test, whereas dendritic spine density and long-term potentiation (LTP) were reduced in the Sev × 6 group on P35. To determine whether exposure to an enriched environment (EE) would ameliorate sevoflurane’s neurotoxic effects, offspring from another Sev × 6 group were exposed to either a standard environment (SE) or an EE. Lower error rates and greater dendritic spine densities and LTP were found in the Sev × 6 + EE vs. Sev × 6 + SE group. Collectively, we showed that exposing rats to 1 MAC sevoflurane for 3 h during late pregnancy increased neuronal apoptosis in neonates but did not impair neuronal development or cognitive function in juvenile rats, whereas a 6-h exposure impaired neuronal development and cognitive function in juvenile rats, effects that were attenuated by an EE. Keywords Cognitive function · Enriched environment · Late-pregnancy · Neuronal development · Offspring · Sevoflurane
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s10571-020-00821-6) contains supplementary material, which is available to authorized users. * Haiyun Wang [email protected]
1
Department of Anesthesiology, The Third Central Clinical College of Tianjin Medical University, Tianjin Third Central Hospital, Nankai University Affinity the Third Central Hospital, Tianjin Institute of Hepatobiliary Disease, Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Tianjin 300170, China
2
Department of Anesthesiology, Tianjin Central Hospital of Gynecology and Obstetrics, Tianjin Key Laboratory of Human Development and Reproductive Regulation, Tianjin 300100, Chin
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