Erythropoietin protects the in vitro blood-brain barrier against VEGF-induced permeability

The blood–brain barrier (BBB) ensures the homeostasis of the brain microenvironment, mostly through complex tight junctions between brain endothelial cells that prevent the passage of hydrophilic molecules from blood to brain and vice versa. A recent study has shown in vivo that systemic administrat...

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Bibliographic Details
Published in:The European journal of neuroscience 2003-11, Vol.18 (9), p.2538-2544
Main Authors: Martínez-Estrada, Ofelia María, Rodríguez-Millán, Elisabeth, González-de Vicente, Esther, Reina, Manuel, Vilaró, Senén, Fabre, Myriam
Format: Article
Language:English
Subjects:
Animals
Astrocytes - physiology
Blood-Brain Barrier - drug effects
Blood-Brain Barrier - metabolism
Blood-Brain Barrier - physiology
Blotting, Western
bovine blood-brain barrier
Brain - physiology
Capillary Permeability - drug effects
Capillary Permeability - physiology
Cattle
Coculture Techniques
Endothelial Cells - drug effects
Endothelial Cells - metabolism
erythropoietin
Erythropoietin - pharmacology
Erythropoietin - physiology
Fluorescent Antibody Technique
junction proteins and permeability
Neuroprotective Agents - pharmacology
Nitric Oxide Synthase - drug effects
Nitric Oxide Synthase - metabolism
Rats
Receptors, Erythropoietin - metabolism
Receptors, Erythropoietin - physiology
Tight Junctions - drug effects
Vascular Endothelial Growth Factor A - metabolism
Vascular Endothelial Growth Factor A - pharmacology
Vascular Endothelial Growth Factor A - physiology
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Summary:The blood–brain barrier (BBB) ensures the homeostasis of the brain microenvironment, mostly through complex tight junctions between brain endothelial cells that prevent the passage of hydrophilic molecules from blood to brain and vice versa. A recent study has shown in vivo that systemic administration of erythropoietin (Epo) protects against brain injury. Using an in vitro model of the bovine BBB, we observed that the expression of the Epo receptor is modulated by its ligand and hypoxic stimuli such as vascular endothelial growth factor (VEGF) treatment. In addition, Epo protects against the VEGF‐induced permeability of the BBB, decreases the levels of endothelial nitric oxide synthase and restores junction proteins. The kinetic transport experiments revealed the capacity of Epo to cross the in vitro BBB in a saturable and specific way. Our results suggest a new mechanism for Epo‐induced neuroprotection, in which circulating Epo controls and maintains the BBB through an Epo receptor signalling pathway and the re‐establishment of cell junctions.
ISSN:0953-816X
1460-9568
DOI:10.1046/j.1460-9568.2003.02987.x