Animal and human stroke studies suggest a causal predictive relationship between early (within 4–5 hours of stroke onset) ischemic BBB damage and tPA-associated ICH5, 6, 7, 8, 9, in which the ischemic brain regions with compromised BBB at the time of tPA administration are found to be at high risk of hemorrhagic transformation at later times during thrombolytic reperfusion. This evidence concerns the gene PLAT and Stroke.