| First Author | Zhao L | Year | 2015 |
| Journal | Neurobiol Aging | Volume | 36 |
| Issue | 11 | Pages | 2963-2971 |
| PubMed ID | 26248866 | Mgi Jnum | J:232257 |
| Mgi Id | MGI:5776414 | Doi | 10.1016/j.neurobiolaging.2015.07.016 |
| Citation | Zhao L, et al. (2015) Matrix metalloproteinase 9-mediated intracerebral hemorrhage induced by cerebral amyloid angiopathy. Neurobiol Aging 36(11):2963-2971 |
| abstractText | Cerebral amyloid angiopathy (CAA), the deposition of amyloid-beta in cerebrovascular walls, is the most common cause of lobar hemorrhagic stroke. Previous studies show that cerebrovascular amyloid-beta induces expression and activation of matrix metalloproteinase 9 (MMP-9) in cerebral vessels of amyloid precursor protein transgenic mice. Here, we extended these findings and evaluated MMP-9 expression in postmortem brain tissues of human CAA cases. MMP-9 colocalized with CAA, correlated with the severity of the vascular pathology, and was detected in proximity to microbleeds. We characterized a novel assay using longitudinal multiphoton microscopy and a novel tracer to visualize and quantify the magnitude and kinetics of hemorrhages in three dimensions in living mouse brains. We demonstrated that topical application of recombinant MMP-9 resulted in a time- and dose-dependent cerebral hemorrhage. Amyloid precursor protein mice with significant CAA developed more extensive hemorrhages which also appeared sooner after exposure to MMP-9. Our data suggest an important role for MMP-9 in development of hemorrhages in the setting of CAA. Inhibition of MMP-9 may present a preventive strategy for CAA-associated hemorrhage. |
