Dose-dependent effects of insulin-like growth factor (IGF-1) delivered by central infusion on hippocampal neurogenesis and memory retention after controlled cortical impact (CCI). (A) Representative images of doublecortin (DCX; green) immunoreactivity in the ipsilateral hippocampus of vehicle (Veh) and IGF-1–infused CCI-injured mice at 7 days post-injury. CCI + Veh mice exhibited a robust loss of DCX immunoreactivity in the dentate gyrus granular layer. DCX immunoreactivity appeared to increase in a dose-dependent manner in CCI + IGF-1 mice. Granular layer (GL) and hilus (H). Scale bar represents 50 μm. (B) In the hippocampus ipsilateral to impact, immature neuron density increased as a function of IGF-1 infusate concentration, peaking at 3 μg/day of IGF-1, which produced a significantly higher density of DCX+ cells compared to vehicle infusion (*p < 0.05). Immature neuron density in the hippocampus contralateral to impact was not significantly changed. (C) Recognition indices (% time exploring novel object) at 3 and 7 days post-CCI. Brain-injured mice receiving vehicle or 0.3 μg/day of IGF-1 performed at chance levels, whereas CCI mice receiving 1, 3, or 10 μg/day of IGF-1 performed above chance at either 3 days, 7 days, or both time points (+p < 0.05 compared to 50%). Data are presented as mean + SEM (n = 4 vehicle-treated CCI-injured and n = 5/dose IGF-1–treated CCI-injured mice). SEM, standard error of the mean. Color image is available online at www.liebertpub.com/neu