FK 506 protects brain tissue in animal models of stroke

Abstract

THE IMMUNOSUPPRESSANT FK 506 (Tacrolimus, Prograf) is widely used clinically for the treatment of allograft rejection. Preclinical studies have indicated that FK 506 may also be of therapeutic use in a number of other clinical conditions, including reperfusion injury. The beneficial effects of FK 506 have been demonstrated in animal models of ischemia-reperfusion injury in peripheral organs, such as the heart, liver, intestines, and skin and in the brain. Although reperfusion contributes significantly to the ischemic damage observed in the heart, the relevance of this phenomenon has been questioned in the brain. Nevertheless, there are numerous reports to suggest that some neuroprotective agents, including FK 506, are beneficial in the treatment of ischemia-reperfusion injury in the central nervous system. The aim of the present study was two-fold: (i) to address the role of reperfusion injury; and (ii) to compare the efficacy of FK 506 in three animal models of focal cerebral ischemia. We examined the effect of a single administration of FK 506 on the outcome of both transient middle cerebral artery occlusion (MCAO) and permanent MCAO and extended the neuroprotection studies from rats to mice.