BACKGROUND: Brain-derived neurotrophic factor (BDNF) is one of the neurotrophic factors that modulate critical metabolic activities, including apoptosis, proliferation, and differentiation modulation. Although numerous studies have focused on the damaging effects of BDNF on neurons, the underlying relationship between these effects remains unclear. In the present study, we investigated the protective effect of BDNF on neuronal injury induced by ropivacaine and assessed whether it is related to the Akt signaling pathway.

MATERIAL AND METHODS: Human neuroblastoma cell line SH-SY5Y cells were stimulated with ropivacaine at different concentrations to induce neuronal injury. MTT analysis, flow cytometry, immunohistochemistry, qRT-PCR, and Western blot were used to investigate the proliferation activity, apoptotic level, and expression of Akt, PCNA, Bax, Bcl-2, and cleaved caspase-3, collectively demonstrating the underlying regulatory mechanisms.

RESULTS: Compared with the control group, the morphological damage and proliferation inhibition of SH-SY5Y cells induced by ropivacaine were dose-dependent and time-dependent, accompanied by a significant decrease in Akt expression. We treated cells with BDNF or SC79, which is a selective cell-permeable small molecule Akt activator. The results showed that, compared to the ropivacaine group, the morphological damage of neurons was alleviated; cell proliferation activity was enhanced; apoptotic rate was reduced; PCNA, Bcl-2, and phosphorylated Akt expression levels were increased; and Bax and caspase-3 gene and protein expression were decreased. We were able to reverse these effects by administering API-2, an Akt inhibitor.

CONCLUSIONS: BDNF can alleviate ropivacaine-induced neuronal injury by activating Akt signaling pathway, consequently modulating the proliferation and apoptosis of neurons.

Keywords: neuronal migration disorders, Oncogene Protein v-akt, Receptor, trkB, Brain-Derived Neurotrophic Factor, Cell Shape, Neurons, Proliferating Cell Nuclear Antigen, Proto-Oncogene Proteins c-akt, RNA, Messenger, ropivacaine, bcl-2-Associated X Protein