Abstract
Ketamine, a noncompetitive N-methyl D-aspartate (NMDA) receptor antagonist, is widely used in pediatric clinical practice. The neuroprotective and neurotoxic effects of ketamine on brain neurons during development remain controversial. The reason may be related to the different concentrations of ketamine used in practice and the small range of concentrations used in previous studies. In this study, cultured hippocampal neurons were treated with ketamine in a wide range of concentrations to comprehensively observe the effects of different concentrations of ketamine on neurons. We demonstrated that low concentrations of ketamine (10 μM, 100 μM and 1000 μM) promoted neuronal survival (p < 0.05) and reduced neuronal apoptosis (p < 0.05) compared with those of the control group. High concentrations of ketamine (2000 μM, 2500 μM and 3000 μM) reduced neuronal survival (p < 0.05) and promoted neuronal apoptosis (p < 0.05). The p38 MAPK inhibitor SB203580 reduced neuronal apoptosis induced by high concentrations of ketamine (2500 μM) (p < 0.05). Our findings indicate that ketamine exerts a dual effect on the apoptosis of primary cultured fetal rat hippocampal neurons in vitro and that the neurotoxic effects of ketamine are related to activation of the p38 MAPK signaling pathway.
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This work was supported by the Joint Fund for the innovation of science and Technology, Fujian province [Grant number: 2018Y9024].
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Conceptualization: Guo-Hua Wu, Que-Hui Guo, Liang-Cheng Zhang, and Cai-Hou Lin. Data curation: Guo-Hua Wu, Que-Hui Guo, Xiao-Dong Xu, Jian-Chang Lin, and Gui-Ting You ; formal analysis: Guo-Hua Wu, Que-Hui Guo, Xiao-Dong Xu, Jian-Chang Lin, Liang-Cheng Zhang, and Cai-Hou Lin. Funding acquisition: Cai-Hou Lin. Investigation: Guo-Hua Wu, Xiao-Dong Xu, Jian-Chang Lin, Gui-Ting You , and Cai-Hou Lin. Methodology: Guo-Hua Wu, Que-Hui Guo, Xiao-Dong Xu, Liang-Cheng Zhang, and Cai-Hou Lin. Project administration: Guo-Hua Wu, and Liang-Cheng Zhang. Supervision: Que-Hui Guo, and Cai-Hou Lin. Visualization: Guo-Hua Wu, Que-Hui Guo, Liang-Cheng Zhang, and Cai-Hou Lin. Writing - original draft; writing - review & editing: Guo-Hua Wu, Que-Hui Guo, Xiao-Dong Xu, Jian-Chang Lin, Gui-Ting You , Liang-Cheng Zhang, and Cai-Hou Lin.
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Wu, GH., Guo, QH., Xu, XD. et al. Ketamine exerts dual effects on the apoptosis of primary cultured hippocampal neurons from fetal rats in vitro. Metab Brain Dis 38, 2417–2426 (2023). https://doi.org/10.1007/s11011-023-01236-0
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DOI: https://doi.org/10.1007/s11011-023-01236-0