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Lithium Treatment Prevents Apoptosis in Neonatal Rat Hippocampus Resulting from Sevoflurane Exposure

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Abstract

We aimed to observe the therapeutic effects of lithium on inhalational anesthetic sevoflurane-induced apoptosis in immature brain hippocampus. From postnatal day 5 (P5) to P28, male Sprague–Dawley pups were intraperitoneally injected with lithium chloride or 0.9 % sodium chloride. On P7 after the injection, pups were exposed to 2.3 % sevoflurane or air for 6 h. Brain tissues were harvested 12 h and 3 weeks after exposure. Cleaved caspase-3, nNOS protein, GSK-3β,p-GSK-3β were assessed by Western blot, and histopathological changes were assessed using Nissl stain and TUNEL stain. From P28, we used the eight-arm radial maze test and step-through test to evaluate the influence of sevoflurane exposure on the learning and memory of juvenile rats. The results showed that neonatal sevoflurane exposure induced caspase-3 activation and histopathological changes in hippocampus can be attenuated by lithium chloride. Sevoflurane increased GSK-3β activity while pretreatment of lithium decreased GSK-3β activity. Moreover, sevoflurane showed possibly slight but temporal influence on the spatial learning and the memory of juvenile rats, and chronic use of lithium chloride might have the therapeutic effect. Our current study suggests that lithium attenuates sevoflurane induced neonatal hippocampual damage by GSK-3β pathway and might improve learning and memory deficits in rats after neonatal exposure.

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Acknowledgments

This work was funded by National Natural Science Foundation of China, Grant No. 81571032 and Guangdong Science Technology Planning Project, Grant No. 2013B051000045.

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    Authors and Affiliations

    1. Department of Anaesthesiology, The First Affiliated Hospital of Sun Yat-Sen University, No. 2nd Zhongshan Road, Guangzhou, 510080, Guangdong, People’s Republic of China

      Xue Zhou, Bao-Long Yuan, Li-Jun Niu, **ao-Yu Yang, Zhi-Bin Zhou & **a Feng

    2. Department of Hepatobiliary Surgery, The Sun Yat-sen Memorial Hospital of Sun Yat-sen University, No. 107 Yanjiang West Road, Guangzhou, 510120, Guangdong, People’s Republic of China

      Wen- da Li

    3. Department of Anesthesiology, Fujian Provincial Hospital, Fujian Provincial Clinical Medical College, Fujian Medical University, Fuzhou, 350001, Fujian, People’s Republic of China

      **ao-Hui Chen

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    All applicable international, national, and Institutional Animal Care and Use Committee at Sun Yat-sen University (Guangzhou, Guangdong, China; No. [2014]A-073) guidelines for the care and use of animals were followed.

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    Xue Zhou and Wen-da Li contributed equally to this work.

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    Zhou, X., da Li, W., Yuan, BL. et al. Lithium Treatment Prevents Apoptosis in Neonatal Rat Hippocampus Resulting from Sevoflurane Exposure. Neurochem Res 41, 1993–2005 (2016). https://doi.org/10.1007/s11064-016-1909-x

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