Protective effect of Ifenprodil on motor neurons in in vitro amyotrophic lateral sclerosis models / 中华神经医学杂志

ABSTRACT

Objective To investigate the protective effect of Ifenprodil on motor neurons in in vitro threo-hydroxyaspartate (THA)-induced amyotrophic lateral sclerosis (ALS) models.Methods THA was added into the isolated culture of brain slices to induce chronic glutamate damage and mimic the typical changes of ALS pathology.Cultured brain slices were separated randomly to 6 different groups,including control group (without THA),THA inducement group (adding 100 μmol/L THA for one week) and THA and Ifenprodil treatment groups (adding 0.1,1,10 and 100 μmol/L of Ifenprodil 2 h before 100 μmol/L THA inducement); 6 culture dishes were employed in each group.According to PI fluorescence intensity,the most effective concentration of Ifenprodil was selected.The concentration of malonaldehyde (MDA) in supematant of cultured tissues was evaluated by MDA testing kit and the protein expression of cysteine-aspartic proteases-3 (caspase-3) in motor cortex was tested by Western blotting at different injury times.Results PI staining showed that 10 μmol/L Ifenprodil could produce prominent protective effect on motor neurons in the ALS models.Levels of MDA in supernatant and activated 17KD caspase-3 in the THA treatment group obviously increased as compared with those in the other groups (P＜0.05); 10 μmol/L Ifenprodil could block the increment of MDA and activated caspase-3 levels effectively.Conclusion Ifenprodil can effectively protect motor neurons in in vitro THA-induced ALS models by reducing oxidative stress and inhibiting caspase-3 activation.