7-Nitroindazole reduces ischemia-induced increment of apoptosis and cell proliferation in the dentate gyrus of rats

Nitric oxide is synthesized from L-arginine by nitric oxide synthase (NOS), and it is a free radical with signaling functions. Neuronal nitric oxide synthase (nNOS) is mainly expressed in the central nervous system, and it has been implicated in the pathogenesis of brain injury such as ischemia. In the present study, the effects of 7-nitroindazole, which specifically inhibits nNOS, on apoptosis and cell proliferation in the dentate gyrus after transient global ischemia in gerbils were investigated. Enhanced apoptotic neuronal cell death and cell proliferation were observed in the dentate gyrus of ischemic gerbils. However, 7-nitroindazole suppressed the ischemia-induced apoptosis and cell proliferation. These results suggest that 7-nitroindazole has an inhibitive effect on apoptosis and cell proliferation following transient global ischemia. The present study shows that nitric oxide, the synthesis of which is augmented by ischemia, plays an important role in the regulation of apoptosis and cell proliferation following ischemic injury.