Aim:To investigate whether sodium ferulate (SF) can protect cortical neuronsfrom glutamate-induced neurotoxicity and the mechanisms responsible for thisprotection.Methods:Cultured cortical neurons were incubated with 50 μmol/Lglutamate for either 30 min or 24 h,with or without pre-incubation with SF (100,200,and 500 μmol/L,respectively).LY294002,wortmannin,PD98059,and U0126were added respectively to the cells 1 h prior to SF treatment.After incubationwith glutamate for 24 h,neuronal apoptosis was quantified by scoring the per-centage of cells with apoptotic nuclear morphology after Hoechst 33258 staining.After incubation with glutamate for either 30 min or 24 h,cellular extracts wereprepared for Western blotting of active caspase-3,poly (ADP-ribose) polymerase(PARP),μ-calpain,Bcl-2,phospho-Akt,phosphorylated ribosomal protein S6 pro-tein kinase (p70S6K),phospho-mitogen-activated protein kinase kinase (MEK1/2)and phosphorylated extracellular signal-regulated kinase (ERK) 1/2.Results:SFreduced glutamate-evoked apoptotic morphology,active caspase-3 proteinexpression,and PARP cleavage and inhibited the glutamate-induced upregulationof the μ-calpain protein level.The inhibition of the phosphatidylinositol 3-kinase(PI3K) and the MEK/ERK1/2 pathways partly abrogated the protective effect ofSF against glutamate-induced neuronal apoptosis.SF prevented the glutamate-induced decrease in the activity of the PI3K/Akt/p70S6K and the MEK/ERK1/2pathways.Moreover,incubation of cortical neurons with SF for 30 min inhibitedthe reduction of the Bcl-2 expression induced by glutamate.Conclusion:Theresults indicate that PI3K/Akt/p70S6K and the MEK/ERK signaling pathwaysplay important roles in the protective effect of SF against glutamate toxicity incortical neurons. Aim: To investigate whether sodium ferulate (SF) can protect cortical neurons from glutamate-induced neurotoxicity and the mechanisms responsible for this protection. Methods: Cultured cortical neurons were incubated with 50 μmol / L glutamate for either 30 min or 24 h, with or without pre- incubation with SF (100, 200, and 500 μmol / L, respectively). LY294002, Wortmannin, PD98059, and U0126 added to the cells 1 h prior to SF treatment. After incubation with glutamate for 24 h, neuronal apoptosis was quantified by scoring the per -centage of cells with apoptotic nuclear morphology after Hoechst 33258 staining. After incubation with glutamate for either 30 min or 24 h, cellular extracts were prepared for Western blotting of active caspase-3, poly (ADP-ribose) polymerase (PARP) (p70S6K), phospho-mitogen-activated protein kinase kinase (MEK1 / 2) and phosphorylated extracellular signal-regulated kinase (ERK) 1 / 2.Results : SFreduced glutamate-evoked apoptotic morphology, active caspase-3 proteinexpression, and PARP cleavage and inhibited the glutamate-induced upregulation of the mu-calpain protein level. The inhibition of the phosphatidylinositol 3-kinase (PI3K) and the MEK / ERK1 / 2 path partly abrogated the protective effect of SF against glutamate-induced neuronal apoptosis. SF prevented the glutamate-induced decrease in the activity of the PI3K / Akt / p70S6K and the MEK / ERK1 / 2 pathways. More over, incubation of cortical neurons with SF for 30 min inhibited the reduction of the Bcl-2 expression induced by glutamate. Conclusion: The results indicate that PI3K / Akt / p70S6K and the MEK / ERK signaling pathways important roles in the protective effect of SF against glutamate toxicity incortical neurons.