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Tetramethylpyrazine protects neural stem cells against sevoflurane-induced toxicity through Akt/GSK-3β pathway

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Abstract

Sevoflurane, a commonly used anesthetic, has been found to cause neural stem cell (NSC) injury, thereby contributing to neurocognitive impairment following general anesthesia. Tetramethylpyrazine (TMP), one of the most widely used medicinal compounds isolated from a traditional Chinese herb, possess neuroprotective activity. However, its effect on sevoflurane-induced NSC injury remains unclear. NSCs were pretreated with indicated concentrations of TMP for 2 h and then exposed to sevoflurane for 6 h. Cell injury was measured using lactate dehydrogenase (LDH) release assay. Cell viability and proliferation were detected by cell counting kit-8 (CCK-8) assay and 5-bromo-2’-deoxyuridine (BrdU) labeling, respectively. Apoptotic cells were detected using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. The levels of cleaved caspase-3, phosphorylated protein kinase B (Akt) and phosphorylated glycogen synthase kinase-3β (GSK-3β) were detected by western blotting. Our results showed exposure to sevoflurane decreased the viability and proliferation of NSCs, while TMP preserved NSC viability and proliferation after sevoflurane exposure. In addition, the expression of cleaved caspase-3 and TUNEL positive cells were markedly decreased in TMP-treated NSCs compared with the control. Furthermore, pretreatment with TMP significantly increased the levels of phosphorylated Akt and GSK-3β in sevoflurane-injured NSCs. However, an upstream inhibitor of Akt, LY294002 abolished the protective of TMP on the cell viability of NSCs. In conclusion, these findings indicate that TMP protects NSCs from sevoflurane-induced toxicity through Akt/GSK-3β pathway.

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Data availability statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Acknowledgements

The authors thank Dr Haidong Wei for his help in revising the manuscript.

Funding

This study was supported by the National Key Research and Development Program of China (2019YFE0115300), National Natural Science Foundation of China (82071482), the Science and Technology Program Fund of Xi’an (2017115SF/YX009), and the Xi’an People’s Hospital (Xi’an Fourth Hospital) Research Incubation Fund (ZD-2) in China.

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Authors and Affiliations

  1. Department of Anesthesiology, The Second Affiliated Hospital of Xi’an Jiaotong University, 157# West 5 Road, 710004, Xi’an, Shaanxi, China

    Yan Feng, Kui Wang, Ning Wang, Pengyu Jia, Lei Zhang, Haozheng Yuan, Pan Lu, Yang Lu, Hong Zhang, Rong Li, Yan Zhang, Qianqian Li & Pengbo Zhang

  2. Department of Anesthesiology, Xi’an People’s Hospital (Xi’an Fourth Hospital), 710004, Xi’an, Shaanxi, China

    Yan Feng & Lei Zhang

Authors
  1. Yan Feng
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  2. Kui Wang
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  3. Ning Wang
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  4. Pengyu Jia
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  5. Lei Zhang
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  6. Haozheng Yuan
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  7. Pan Lu
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  8. Yang Lu
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  9. Hong Zhang
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  11. Yan Zhang
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  12. Qianqian Li
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  13. Pengbo Zhang
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Contributions

Pengbo Zhang and Kui Wang designed this study. Yan Feng and Ning Wang performed experiments. Pengyu Jia and Lei Zhang collected the data. Haozheng Yuan and Pan Lu analyzed the data. Yang Lu and Hong Zhang wrote this paper. Rong Li and Yan Zhang contributed the methodology. Qianqian Li operated the software.

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Correspondence to Pengbo Zhang.

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Feng, Y., Wang, K., Wang, N. et al. Tetramethylpyrazine protects neural stem cells against sevoflurane-induced toxicity through Akt/GSK-3β pathway. Metab Brain Dis 37, 2457–2466 (2022). https://doi.org/10.1007/s11011-022-01008-2

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