While knockout of MMP-3 in stroke mice reduced the tPA-enhanced risk of ICH, delayed tPA administration (4 h post-MCAO) in the thrombotic ischemic stroke model was found to further augment MMP-3 expression selectively in ECs in the ischemic hemisphere, which suggests the involvement of MMP-3 in disruption of the BBB and ICH. This evidence concerns the gene PLAT and ischemic stroke.