Open Access Proteolytic Extracellular Matrix Fragments Following Ischemic Stroke: New Insights to Potential Therapeutic Targets

Abstract: Stroke is the leading cause of long-term disability and the third leading cause of death in the United States. The sudden disruption of blood flow that occurs following ischemic stroke ultimately leads to neuronal death, breakdown of the blood brain barrier, and proteolytic processing of the surrounding extracellular matrix (ECM). Within 3 days after ischemic stroke, new blood vessels begin to form around (ischemic penumbra) the site of injury by a process known as angiogenesis. Angiogenesis, in turn is regulated by a number of growth factors and by processed biologically active fragments of the ECM. Unfortunately, current experimental stroke therapies that might enhance post-stroke angiogenesis, including growth factors, pharmaceuticals, and stem cells may engender significant and unacceptable risks. Furthermore, while most other stroke therapies have focused on neuroprotection during the acute phase of stroke injury, we hypothesize that exploiting brain self-repair mechanisms, including ECM matrix fragment generation, may provide better therapies. In this mini-review we will discuss the importance of the ECM following stroke, including the potential role of its proteolytic fragments in modulating angiogenesis and neurogenesis