Abstract
FK506 is an immunosuppressant widely used in liver, kidney and bone marrow transplantation. Recently, some authors have reported on the neuroprotective properties of FK506 in vitro and in vivo, but the cellular mechanisms underlying the neuroprotective action it exercises in experimental stroke remains uncertain.
In former reports, we have already demonstrated that intravenous injection of FK506 (0.3 mg/kg) reduces the ischemic cortical damage when administered immediately after transient middle cerebral artery occlusion (MCAO). The present study invistigates the therapeutic time window for FK506 in transient focal ischemia in rats. The left MCAO were occluded for 2h by intraluminal suture and reperfused for 24h. FK506 reduced the cortical infarction volume by 44% and 45%, when administrated 30 min and 60 min after the onset of ischemia, but had no neuroprotective activity when administrated 120 min after ischemia. This effect is unlikely to be due to the reduction of brain edema, since there was no difference in edema in FK506 treated and vehicle treated groups. These results suggest the therapeutic time window for FK506 administrated intravenously is between 60 min and 120 min, because of efficacy to ameliorate neuronal damage at 60 min but not at 120 min, and that FK506 is a novel candidate for clinical application for ischemic stroke, and is likely to be more effective with less side-effects than present medical strategies for ischemic stroke in human.
