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CNS & Neurological Disorders - Drug Targets


ISSN (Print): 1871-5273
ISSN (Online): 1996-3181

Targeting Extracellular Matrix Proteolysis for Hemorrhagic Complications of tPA Stroke Therapy

Author(s): Xiaoying Wang, Anna Rosell and Eng H. Lo

Volume 7, Issue 3, 2008

Page: [235 - 242] Pages: 8

DOI: 10.2174/187152708784936635

Price: $65


To date, tPA-based thrombolytic therapy is the only FDA-approved treatment for achieving vascular reperfusion and clinical benefit, but this agent is given to only about 2-5% of stroke patients in the United States of America. This may be related, in part, to the elevated risks of symptomatic intracranial hemorrhage, and the consequently reduced therapeutic time window. Recent efforts have aimed at identifying new combination strategies that might increase thrombolytic efficacy of tPA to benefit reperfusion, while reducing its associated neurotoxicity and hemorrhagic complications. Emerging experimental studies demonstrate that the breakdown of neurovascular matrix initiates blood – brain barrier disruption with edema and/or hemorrhage. Perturbation of extracellular homeostasis triggered by dysregulated extracellular proteases may underlie processes responsible for the hemorrhagic complications of thrombolytic stroke therapy. This short review summarizes experimental investigations of this field in pre-clinical stroke models. The data strongly suggest that targeting the extracellular matrix proteolytic imbalance within the neurovascular unit may provide new approaches for improving the safety and efficacy of thrombolytic reperfusion therapy of stroke.

Keywords: tPA, extracellular protease, matrix metalloproteinases, extracellular proteolysis, blood-brain barrier, intracerebral hemorrhage, combination therapy

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