Abstract
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
CNS & Neurological Disorders - Drug Targets
Title: Targeting Extracellular Matrix Proteolysis for Hemorrhagic Complications of tPA Stroke Therapy
Volume: 7 Issue: 3
Author(s): Xiaoying Wang, Anna Rosell and Eng H. Lo
Affiliation:
Keywords: tPA, extracellular protease, matrix metalloproteinases, extracellular proteolysis, blood-brain barrier, intracerebral hemorrhage, combination therapy
Abstract: 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.
Export Options
About this article
Cite this article as:
Wang Xiaoying, Rosell Anna and Lo H. Eng, Targeting Extracellular Matrix Proteolysis for Hemorrhagic Complications of tPA Stroke Therapy, CNS & Neurological Disorders - Drug Targets 2008; 7 (3) . https://dx.doi.org/10.2174/187152708784936635
DOI https://dx.doi.org/10.2174/187152708784936635 |
Print ISSN 1871-5273 |
Publisher Name Bentham Science Publisher |
Online ISSN 1996-3181 |
Call for Papers in Thematic Issues
Diagnosis and treatment of central nervous system infectious diseases
Infectious diseases of the central nervous system (CNS) can be divided into bacterial, tuberculous, viral, fungal, parasitic infections, etc. Early etiological treatment is often the most crucial means to reduce the mortality rate of patients with central nervous system infections, reduce complications and sequelae, and improve prognosis. The initial clinical ...read more
Techniques of Drug Repurposing: Delivering a new life to Herbs & Drugs
Of late, with the adaptation of innovative approaches and integration of advancements made towards medical sciences as well as the availability of a wide range of tools; several therapeutic challenges are being translated into viable clinical solutions, with a high degree of efficacy, safety, and selectivity. With a better understanding ...read more
Trends and perspectives in the rational management of CNS disorders
Central nervous system (CNS) diseases enforce a significant global health burden, driving ongoing efforts to improve our understanding and effectiveness of therapy. This issue investigates current advances in the discipline, focusing on the understanding as well as therapeutic handling of various CNS diseases. The issue covers a variety of diseases, ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Mechanism and Inhibition of Matrix Metalloproteinases
Current Medicinal Chemistry Reactive Oxygen Species, Vascular Disease and Cardiovascular Surgery
Current Vascular Pharmacology Kinase Inhibitor Conjugates
Current Pharmaceutical Design Post-locoregional Therapy MRI Evaluation of Malignant Liver Lesions
Current Cancer Therapy Reviews The Saphenous Vein as a Bypass Conduit: The Potential Role of Vascular Nerves in Graft Performance
Current Vascular Pharmacology Enhanced Neuroprotection of Ischemic Stroke Based on Liposomal Drug Delivery System Loading a Novel Uncoupler of Ischemia-induced nNOSPSD- 95
Current Signal Transduction Therapy Thiazolidinediones and Cardiovascular Risk — A Question of Balance
Current Cardiology Reviews The Role of Macrophage Migration Inhibitory Factor in Critical Illness
Mini-Reviews in Medicinal Chemistry Arterial Hyperoxia in Severe Head Injury: A Useful or Harmful Option?
Current Pharmaceutical Design Recent Developments in the Regulation of Monoamine Oxidase Form and Function: Is the Current Model Restricting Our Understanding of the Breadth of Contribution of Monoamine Oxidase to Brain [dys]Function?
Current Topics in Medicinal Chemistry The Bax Inhibitor-1 (BI-1) Family in Apoptosis and Tumorigenesis
Current Molecular Medicine Curcumin Alleviates Cerebral Ischemia-reperfusion Injury by Inhibiting NLRP1-dependent Neuronal Pyroptosis
Current Neurovascular Research The Role of Selectins During Lung Inflammation and Their Potential Impact for Innovative Therapeutic Strategies
Current Respiratory Medicine Reviews The Atherosclerosis Time-Line and the Role of the Endothelium
Current Medicinal Chemistry - Immunology, Endocrine & Metabolic Agents Amyloid β -Protein Assembly as a Therapeutic Target of Alzheimers Disease
Current Pharmaceutical Design Medicinal Plants in Neurodegenerative Diseases: Perspective of Traditional Persian Medicine
Current Drug Metabolism From Concept to Reality: The Long Road to c-Met and RON Receptor Tyrosine Kinase Inhibitors for the Treatment of Cancer
Anti-Cancer Agents in Medicinal Chemistry Unfolded Protein Response as a Therapeutic Target in Cardiovascular Disease
Current Topics in Medicinal Chemistry A Facile “Click Chemistry” Approach to Novel Flavonol Glycoconjugates and Their Cytotoxic Activity
Letters in Organic Chemistry Non-Transferrin Bound Iron - Determination in Biological Material and Clinical Implications
Current Pharmaceutical Analysis