tPA has a therapeutic role in AIS, but it leads to a significant rate of ICH. Administration of rtPA accelerates the conversion of plasminogen to plasmin, which in turn lyses fibrin to its degradation products. At the same time, tPA induces phosphorylation (P) of occludin, which increases BBB permeability. AIS also upregulates occludin phosphorylation and BBB permeability. Both pathways of occludin phosphorylation and increased BBB permeability increase the risk of ICH in patients presenting with AIS.