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.
Tokime
T
T
Department of Neurosurgery, Faculty of Medicine, Kyoto University, Japan.
Nozaki
K
K
Kikuchi
H
H
D000818:Animals; D016923:Cell Death / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D005849:Gerbillinae; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007191:Indazoles / Q000627:therapeutic use; D002546:Ischemic Attack, Transient / Q000517:prevention & control*; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000473:pathology; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D016548:Prosencephalon / Q000098:blood supply; D016559:Tacrolimus / Q000627:therapeutic use*
D004791:Enzyme Inhibitors; D007166:Immunosuppressive Agents; D007191:Indazoles; D018696:Neuroprotective Agents; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; C080122:7-nitroindazole; D016559:Tacrolimus