Matrix metalloproteinase proteolysis after stroke: a surrogate indicator for early diagnosis and validation of treatment

Abstract

Matrix metalloproteinases (MMPs) are a family of endoproteaseses that have various functions from development to disease. They are also believed to play critical roles in the central nerve system for the pathogenesis of stroke. In ischemic stroke, MMP 9 is involved in neuronal apoptosis, edema, and hemorrhagic transformation. In stroke models, MMPs degrade ECM components and disrupt neurovascular integrity, resulting in blood-brain barrier (BBB) disruption and hemorrhage which further damage to the ischemic area. There are experimental pharmacological treatments with MMP inhibitors that decrease the extent of neuronal apoptosis and hemorrhage. Recently we tested a new class of mechanism-based MMP-9 specific inhibitors SB-3CT. Our hypothesis is that MMP-9 causes proteolytic changes resulting in neurovascular damage after focal cerebral ischemia in mice. Inhibition of MMP proteolysis with SB-3CT, should result in decreased apoptosis of neurons and improved behavioral outcomes.