Dexmedetomidine Protects Cortical Neurons from Propofol-Induced Apoptosis via Activation of Akt-IKK-NF-κB Signaling Pathway by α 2A -adrenoceptor.

Context: Propofol can induce neuroapoptosis. It has been reported that dexmedetomidine (DEX) has a protective effect on propofol-induced neuroapoptosis, but the specific mechanism needs to be further explored to provide a theoretical basis for their combined use.
Objective: We aimed to explore the neuroprotective effect of DEX on primary cortical neurons treated by propofol and to elucidate the underlying mechanistic pathways.
Methods: Cortical neurons were isolated from fetal rats and treated with propofol. MTT assays were performed to detect cell viability, α-tubulin immunofluorescent assays were conducted to observe cell abnormalities, and c-caspase3 immunofluorescent assays and flow cytometry were performed to examine cell apoptosis. Further, neurons were cotreated with propofol and DEX to study DEX's neuroprotective effects on propofol-caused neuronal injuries. Finally, the α _2A -adrenoceptor was knocked out and/or the Akt activator (SC-79) was added to cells co-treated with propofol and DEX. The expression levels of Akt-IKK-NF-κB pathway-related proteins were detected by western blot.
Results: Propofol decreased cell viability in a dose-dependent manner, triggered apoptosis, caused morphological abnormalities and down-regulated the phosphorylation levels of Akt, IKK, NF-κB and IκB in cortical neurons. DEX ameliorated the decrease of cell viability, alleviated neuronal apoptosis and promoted the downregulated expression levels of p-Akt, IKK, NF-κB, and IκB proteins which had been induced by propofol treatment. Western blot findings following the transfection of α _2A -siRNA and the addition of SC-79 suggested that DEX's neuroprotective functions arose from the stimulation of α _2A -adrenoceptors to activate the Akt-IKK-NF-κB signal pathway.
Conclusion: DEX protected neurons against propofol-induced apoptosis via activation of the Akt-IKK-NF-κB signal pathway through α _2A -adrenoceptors.
(© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)