Synaptic reorganization plays a very important role in brain adaptations to environmental stimuli, diseases, and aging processes. The NMDA model of excitotoxic injury was used to investigate the long-term molecular changes in the surviving neural cells in the mouse hippocampus. We demonstrated that a single intraperitoneal injection of NMDA produces persistent expression of c-fos, c-jun, Fas, and Fas ligand(FasL) mRNA in the hippocampus for 5 months. To determine the cellular origin of those gene transcripts in our in vivo model, a glial cell line and primary fetal neuronal culture were used to investigate the inducibility of the c-fos, c-jun, Fas, and FasL mRNA by NMDA. Both c-fos and Fas mRNA expression was observed in the NMDA-treated glial or neuronal cultures; however, c-jun and FasL mRNA was undetectable in this study. In our in vivo model, mossy fiber sprouting and apoptosis were also observed up to 40 days after the NMDA injection. Therefore, we hypothesize that the observed long-term expression of c-fos, c-jun, Fas, and FasL mRNAs may reflect the ongoing synaptic reorganization.