Neuroprotective effects of an immunosuppressant agent on diffusion/perfusion mismatch in transient focal ischemia

The immunosuppressant FK506 (tacrolimus) exerts potent neuroprotection following focal ischemia in animals; however, the separate effects of FK506 on the ischemic core and penumbra have not been reported. The ischemic penumbra is clinically defined as the difference between a large abnormal area on perfusion-weighted imaging (PWI) and a smaller lesion on diffusion-weighted imaging (DWI). The goal of this study was to determine the effect of FK506 on DWI/PWI match and mismatch areas in transient focal ischemia in rats. Twelve rats were subjected to 1 hr of transient middle cerebral artery (MCA) occlusion, and given an intravenous injection of a placebo (N = 6) or 1 mg/kg FK506 (N = 6) immediately before reperfusion. Magnetic resonance imaging (MRI) was performed during MCA occlusion, and 0.5, 1, and 24 hr after reperfusion. FK506 significantly protected the ischemic brain only in the mismatch cortex where the initial apparent diffusion coefficient (ADC) was normal and there was a mild reduction of cerebral blood flow (CBF). This is the first report to describe the protective effects of FK506 on ischemic penumbra, as measured by DWI/PWI mismatch. The findings provide direct evidence for the utility of DWI/PWI mismatch as a guideline for therapeutic intervention with FK506.