There is a growing body of evidence that suggests common complications in regional anesthesia, including transient neurological syndrome, are caused by the neurotoxicity of local anesthetics (LAs). Ropivacaine is thought to be one of the safest LAs, however, there have been several studies detailing possible neurotoxic effects. At present, the exact molecular mechanism of ropivacaine-mediated neurotoxicity is unknown. The present study was designed to explore the possible mechanisms underlying the neurotoxicity of ropivacaine. The neurotoxic effects of ropivacaine were assessed in spinal cord by TUNEL staining for apoptosis and in cultured PC12 cells by cell viability assays. Protein kinase B (Akt) activation was evaluated by immunoblotting. Ropivacaine promoted apoptosis and caused cell death in a treatment group compared with a sham-operated group. Furthermore, ropivacaine significantly diminished Akt activation. There were significantly lower Akt levels in cells exposed to ropivacaine compared with controls. The present study demonstrated ropivacaine neurotoxicity in vivo and in vitro, mediated by the Akt signaling pathway. The neurotoxicity of apoptosis with concomitant cell death, mediated by ropivacaine, may offer an explanation for its adverse effects (e.g., transient neurological syndrome).
Keywords: local anesthetic; neurotoxicity; apoptosis; Akt; PC12 cells.