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Updated: Mar 30, 2026
Improved Method for the Preparation of a Human Cell-based, Contact Model of the Blood-Brain Barrier
Published on: November 12, 2013
Endothelial tPA-dependent recruitment of microglia to vessels protects the blood-brain barrier after stroke
Tamara Etuzé1, Louis Fosset1, Denis Vivien2,3
1Physiopathology and Imaging of Neurological Disorders (PhIND), INSERM UMR-S U1237, Université de Caen Normandie, Normandie Université, Institut Blood and Brain @ Caen-Normandie, Cyceron, Boulevard Becquerel, Caen, 14074, France.
Background:
Ischemic stroke is one of the leading causes of death and disability worldwide and thrombolysis, with tissue-type plasminogen activator (tPA) or its mutants, remains the only pharmacological treatment available for the acute phase. In this study, we hypothesised that endothelial tPA plays a key role in modulating the microglial response and maintaining blood brain barrier (BBB) integrity after stroke.
Methods:
Using a mouse model with endothelial-specific deletion of tPA (VeCadCre - tPAFlox), combined with a thrombotic stroke model and high-resolution imaging, we investigated the effects of endothelial tPA on vascular inflammation and microglial activation.
Results:
Our results demonstrate that microglia-vessel contacts increase post-stroke. Notably, deletion of endothelial tPA reduces vascular cell adhesion molecule 1 (VCAM1) expression and is associated with decreased microglial activation and fewer microglia-vessel contacts. Interestingly, endothelial tPA deletion also leads to increased BBB permeability and a heightened risk of haemorrhagic transformation following stroke.
Conclusions:
Collectively, these findings indicate that endothelial tPA promotes microglial recruitment to blood vessels and plays a protective role in preserving BBB integrity after ischemic stroke.
