Abstract
Background
The aim of the study was to determine the effects of repeated anesthesia exposure across postnatal development.
Methods
Seventy-two newborn Sprague–Dawley rats were randomly divided into Sev group and Con-aged group. Sev groups were exposed to 2.6% sevoflurane for 2 h on postnatal day (P) 7, P14, and P21; the Con groups only received carrier gas for 2 h. Learning and memory were evaluated using the MWM test at P31 (juvenile), P91 (adult), and 18 months postnatally (aged). The relative expression of APP and Mapt mRNA was detected by RT-PCR, while Aβ, tau, and P-tau protein levels were analyzed by immunohistochemistry.
Results
After repeated inhalation of sevoflurane, MWM test performance was significantly decreased in the Sev-aged group compared to the Con-aged group (P > 0.05). The relative expression of APP and Mapt mRNA was not significantly different between groups in each growth period (P > 0.05). The tau expression in the juvenile hippocampal CA1, CA3, and dentate gyrus regions increased markedly in the Sev group, while P-tau only increased in the hippocampal CA3 region in the Sev-adult group. The expression of tau, P-tau, and Aβ in the hippocampal regions was upregulated in the Sev-aged group.
Conclusions
Multiple exposures to sevoflurane across postnatal development can induce or aggravate cognitive impairment in old age.
Impact
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Whether multiple sevoflurane exposures across postnatal development cause cognitive impairment in childhood, adulthood, or old age, as well as the relationship between sevoflurane and the hippocampal Aβ, tau, and P-tau proteins, remains unknown.
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This study’s results demonstrate that multiple exposures to sevoflurane across postnatal development do not appear to affect cognitive function in childhood and adulthood; however, multiple exposures may lead to a cognitive function deficit in old age.
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The underlying mechanism may involve overexpression of the tau, P-tau, and Aβ proteins in the hippocampus.
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Funding
This work was supported by the National Natural Science Foundation of China [No. 81360180], [No. 81960214], [No. 82160223].
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Participated in experimental manipulation and manuscript writing: Y.Z.; data analysis and interpretation: C.Z.; Participated in experimental manipulation, collection and assembly of data: Y.W. C.T. J.R. and M.W.; Drawing Images and final approval of undefined manuscript: D.L. Conception, design and administrative support: Z.Z.
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This study was conducted in accordance with the Declaration of Helsinki and with approval from the Animal Ethics Committee of Zunyi Medical College, Zunyi, China on January 20, 2014 (Project No. 81360180), Animal Ethics Committee of Zunyi Medical University, Zunyi, China on March 11, 2019 (No. (2019)2-044), Animal Ethics Committee of Zunyi Medical University, Zunyi, China on February 18, 2021 (No. (2021)2-172).
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Zhong, Y., Zhang, C., Wang, Y. et al. Multiple exposures to sevoflurane across postnatal development may cause cognitive deficits in older age. Pediatr Res 93, 838–844 (2023). https://doi.org/10.1038/s41390-022-01943-x
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DOI: https://doi.org/10.1038/s41390-022-01943-x
