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.
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We thank Yuhua Cui for her assistance in designing of the figures.
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This work was supported by grants from the National Natural Science Foundation of China [Grant No. 81571054] and Tianjin Major Support Program of Science and Technology [Grant No. 18YFZCSY00530].
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All authors have made substantive intellectual contributions to the manuscript. ZY and HW designed the study. JW and JW were responsible for conducting the study and analyzing the data. ZY and PZ wrote the manuscript. JC revised the manuscript. All authors have seen the original study data, reviewed the data analysis, and approved the final manuscript.
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Yu, Z., Wang, J., Wang, H. et al. Effects of Sevoflurane Exposure During Late Pregnancy on Brain Development and Beneficial Effects of Enriched Environment on Offspring Cognition. Cell Mol Neurobiol 40, 1339–1352 (2020). https://doi.org/10.1007/s10571-020-00821-6
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DOI: https://doi.org/10.1007/s10571-020-00821-6