Neuroprotective effect of FK506, an immunosuppressant, on transient global ischemia in gerbil.

Delayed neuronal death (DND) in CA1 region after transient global ischemia is a well-known phenomenon, but its mechanism has not been clarified. In order to examine the involvement of nitric oxide (NO) in DND, 7-nitro indazole (7NI), a selective neuronal NO synthase (nNOS) inhibitor, and FK506, an immunosuppressant which also inhibits nNOS, were administered intraperitoneally during and after transient global ischemia in gerbil. FK506 moderately ameliorated DND in a dose-dependent manner. However, 7NI showed only minor neuroprotective effects. These results show that DND is not mainly mediated by NO production via nNOS, and FK506 acts as a neuroprotective agent via unknown pathways other than nNOS inhibition.