fig3

Figure 3. Mechanisms by which tPA may disrupt the blood-brain barrier. (1) tissue-type plasminogen activator(tPA) released from neurons cleaves lipoprotein receptor-related protein-1 (LRP-1) to activate an NF-κB signaling cascade resulting in the production of MMP-9. tPA and LRP-1 can bind amyloid beta, which facilitates Aβ endocytosis across the blood-brain barrier (BBB). (2) Neuronal tPA degrades platelet-derived growth factor-CC (PDGF-CC) to release the active ligand for PDGF receptor-α (PDGFR-α) on astrocytic endfeet, causing them to retract from endothelial cells. (3) Plasma tPA activates plasmin to directly produce bradykinin that activates bradykinin 2 receptor (B2R) receptor on endothelial cells. (4) Plasma tPA cleaves plasminogen to generate plasmin that indirectly upregulates bradykinin expression through plasma kallikrein (PKal). Created with BioRender.com.