In Vivo and In Vitro Treatment With Edaravone Promotes Proliferation of Neural Progenitor Cells Generated Following Neuronal Loss in the Mouse Dentate Gyms

Edaravone is clinically used in Japan for treatment of patients with acute cerebral infarction. To clarify the effect of edaravone on neurogenesis in the hippocampus following neuronal injury in the hippocampal dentate gyms, we investigated the effect of in vitro and in vivo treatment with edaravone on the proliferation of neural stem/progenitor cells prepared from the mouse dentate gyms damaged by trimethyltin (TMT). Histological assessment revealed the presence of large number of nestin(+) cells in the dentate gyms on days 3 - 5 post-TMT treatment. We prepared cells from the dentate gyms of naive, TMT-treated mice or TMT/edaravone-treated mice. The cells obtained from the dentate gyms of TMT-treated animals were capable of BrdU incorporation and neurosphere formation when cultured in the presence of growth factors. The TMT-treated group had a larger number of nestin(+) cells and nestin(+)GFAP(+) cells than the naive one. Under the culture condition used, sustained exposure of the cells from the damaged dentate gyms to edaravone at 10(-11) and 10(-8) M promoted the proliferation of nestin(+) cells. The systemic in vivo treatment with edaravone for 2 days produced a significant increase in the number of nestin(+) cells among the cells prepared from the dentate gyms on day 4 post-TMT treatment, and as well as one in the number of neurospheres formed from these cells in the culture. Taken together, our data indicated that edaravone had the ability to promote the proliferation of neural stem/progenitor cells generated following neuronal damage in the dentate gyms.