Attenuate Effect of LiCl on Neuronal Apoptosis Induced by Sevoflurane

OBJECTIVE To examine the effects of LiCl on developmental sevoflurane-induced neuronal apoptosis and the role of β-arrestin2/AKT signaling pathway. METHODS The developmental sevoflurane neurotoxicity model was established by exposure of primary hippocampal neurons (7 days in vitro) and Sprague-Dawley rat pups (7 postnatal days) with sevoflurane (3%, 6 h). The cells were treated with LiCl or combined with β-arrestin2 siRNA transfection. The neuronal apoptosis was analyzed by flow cytometry (FCM), MTT and Hoechst-staining. The relative expressions of total AKT, Phospho-AKT, total GSK3β, Phospho-GSK3β, Bax and Bcl-2 were determined by western blot. The emotional and spatial cognitive functions were examined by fear conditioning and Morris water maze. RESULTS Sevoflurane exposure (3%, 6 h) significantly enhanced the neuronal apoptosis, which could be ameliorated by LiCl. Sevoflurane decreased the expressions of Phospho-AKT and Bcl-2, but increased Phospho-GSK3β and Bax. LiCl significantly elevated the expressions of Phospho-AKT and Bcl-2, but decreased Phospho-GSK3β and Bax. The neuronal protective role of LiCl was abolished by β-arrestin2 siRNA transfection, SH-5 or LY294002. In addition, LiCl significantly improved the emotional and spatial cognitive disorders induced by postnatal sevoflurane exposure. CONCLUSION Application of LiCl can prevent developmental sevoflurane neurotoxicity, and the β-arrestin2-dependent AKT/GSK3β signaling pathway may be involved in this process.