Injury conditioned media (ICM) has a detrimental effect on neuronal progenitor cell survival and differentiation, via a RAGE-dependent mechanism. (A) Exposure to ICM does not result in a significant change in total cell count; (B) ICM exposure results in a significant decrease in both neuronal cell survival (Tuj1+ cells/mm2; * p < 0.05) and differentiation (%Tuj1/DAPI cells; * p < 0.05); (C) Representative immunofluorescence microscopy images of rat cortical neural stem cell/progenitor cell cultures demonstrate RAGE expression in Sox2+ cells (yellow arrows); (D,E) Addition of glycyrrhizin, a RAGE antagonist, rescued the anti-neurogenic effects seen with addition of ICM (** p < 0.01, **** p < 0.0001); (F) Representative immunofluorescence microscopy images of rat cortical neural stem cell/progenitor cell cultures exposed to CCM and ICM in the absence or presence of glycyrrhizin (Tuj1- green, DAPI- blue). Scale bars 100 µm, 20× magnification in microscopy images. Two-way ANOVA used for statistical analysis with p < 0.05 considered significant. n: 3–4 animals, four wells per condition and 2 repeats per experiment. Abbreviations: CCM- control condition media; ICM—injury condition media.