TPA Modulation of the Blood-Brain Barrier: A Unifying Explanation for the Pleiotropic Effects of TPA in the CNS

Overview

Journal Semin Thromb Hemost

Publisher Thieme

Specialties Cardiology & Vascular Diseases
Hematology

Date 2016 Sep 28

PMID 27677179

Citations 29

Authors

Linda Fredriksson

Daniel A Lawrence

Robert L Medcalf

Affiliations

Soon will be listed here.

Abstract

The plasminogen activation (PA) system is best known for its role in fibrinolysis. However, it has also been shown to regulate many nonfibrinolytic functions in the central nervous system (CNS). In particular, tissue-type plasminogen activator (tPA) is reported to have pleiotropic activities in the CNS, regulating events such as neuronal plasticity, excitotoxicity, and cerebrovascular barrier integrity, whereas urokinase-type plasminogen activator is mainly associated with tissue remodeling and cell migration. It has been suggested that the role tPA plays in controlling barrier integrity may provide a unifying mechanism for the reported diverse, and often opposing, functions ascribed to tPA in the CNS. Here we will review the possibility that the pleiotropic effects reported for tPA in physiologic and pathologic processes in the CNS may be a consequence of its role in the neurovascular unit in regulation of cerebrovascular responses and subsequently parenchymal homeostasis. We propose that this might offer an explanation for the ongoing debate regarding the neurotoxic versus neuroprotective roles of tPA.

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