Fig. 5. Efficacy on enhancing proliferation of hippocampal neural precursor cells and survival of young hippocampal neurons was compared between NSI-189 and P7C3-A20 at a dose of 10 mg kg⁻¹day⁻¹ administered intraperitoneally.

Representative micrographs of BrdU+ cells in the dentate gyrus are shown above, with quantified data displayed below as mean +/- standard error of the mean (SEM). Proliferation was assayed in animals that had received 3 days of daily P7C3-A20 or NSI-189, followed by a 1 h pulse of of BrdU (150 mg/kg ip) P7C3-A20 elicited no increase in cellular proliferation compared to the level seen in vehicle-treated animals. NSI-189 elevated proliferation of neural precursor cells by approximately 70% relative to vehicle (p < .001) and P7C3-A20-treated mice (p < 0.01). Neuroprotective efficacy for young hippocampal neurons was assayed in animals that received the same pulse of BrdU at the same time as initiation of 15 days of daily treatment with P7C3-A20 or NSI-189. P7C3-A20-treated animals showed a survival rate approximately three times greater than vehicle-treated (p < .0001) and NSI-189-treated (p < .001) animals, with migration of some cells out of the subgranular zone and into the dentate gyrus. Animals treated with NSI-189 showed a minor and non-significant trend towards increased survival, indicating that the proneurogenic efficacy of NSI-189 is likely confined to its pro-proliferative effect on cells. P7C3 compounds increase the net magnitude of hippocampal neurogenesis to a greater extent than NSI-189 by virtue of the unique ability of P7C3 compounds to protect neurons from cell death