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Dexmedetomidine attenuates the neurotoxicity of propofol toward primary hippocampal neurons in vitro via Erk1/2/CREB/BDNF signaling pathways

Authors Tu Y, Liang Y, Xiao Y, Lv J, Guan R, Xiao F, Xie Y, Xiao Q

Received 22 September 2018

Accepted for publication 13 December 2018

Published 19 February 2019 Volume 2019:13 Pages 695—706

DOI https://doi.org/10.2147/DDDT.S188436

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Colin Mak

Peer reviewer comments 2

Editor who approved publication: Dr Anastasios Lymperopoulos


Youbing Tu,1 Yubing Liang,2 Yong Xiao,1 Jing Lv,1 Ruicong Guan,1 Fei Xiao,1 Yubo Xie,1,* Qiang Xiao3,*

1Department of Anesthesiology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China; 2Department of Anesthesiology, The Affiliated Tumor Hospital of Guangxi Medical University, Nanning 530021, China; 3Department of Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China

*These authors contributed equally to this work

Background: Propofol is a commonly used general anesthetic for the induction and maintenance of anesthesia and critical care sedation in children, which may add risk to poor neurodevelopmental outcome. We aimed to evaluate the effect of propofol toward primary hippocampal neurons in vitro and the possibly neuroprotective effect of dexmedetomidine pretreatment, as well as the underlying mechanism.
Materials and procedures: Primary hippocampal neurons were cultured for 8 days in vitro and pretreated with or without dexmedetomidine or phosphorylation inhibitors prior to propofol exposure. Cell viability was measured using cell counting kit-8 assays. Cell apoptosis was evaluated using a transmission electron microscope and flow cytometry analyses. Levels of mRNAs encoding signaling pathway intermediates were assessed using qRT-PCR. The expression of signaling pathway intermediates and apoptosis-related proteins was determined by Western blotting.
Results: Propofol significantly reduced cell viability, induced neuronal apoptosis, and downregulated the expression of the BDNF mRNA and the levels of the phospho-Erk1/2 (p-Erk1/2), phospho-CREB (p-CREB), and BDNF proteins. The dexmedetomidine pretreatment increased neuronal viability and alleviated propofol-induced neuronal apoptosis and rescued the propofol-induced downregulation of both the BDNF mRNA and the levels of the p-Erk1/2, p-CREB, and BDNF proteins. However, this neuroprotective effect was abolished by PD98059, H89, and KG501, further preventing the dexmedetomidine pretreatment from rescuing the propofol-induced downregulation of the BDNF mRNA and p-Erk1/2, p-CREB, and BDNF proteins.
Conclusion: Dexmedetomidine alleviates propofol-induced cytotoxicity toward primary hippocampal neurons in vitro, which correlated with the activation of Erk1/2/CREB/BDNF signaling pathways.

Keywords: hippocampus, propofol, dexmedetomidine, extracellular signal-regulated MAP kinases, cyclic AMP response element-binding protein, brain-derived neurotrophic factor
 

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