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Erythropoietin protects the in vitro blood–brain barrier against VEGF‐induced permeability
Author(s) -
MartínezEstrada Ofelia María,
RodríguezMillán Elisabeth,
Gonzálezde Vicente Esther,
Reina Manuel,
Vilaró Senén,
Fabre Myriam
Publication year - 2003
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1046/j.1460-9568.2003.02987.x
Subject(s) - erythropoietin , blood–brain barrier , tight junction , neuroprotection , microbiology and biotechnology , in vitro , vascular endothelial growth factor , in vivo , receptor , erythropoietin receptor , vascular permeability , chemistry , pharmacology , nitric oxide , endothelial stem cell , biology , cancer research , central nervous system , neuroscience , endocrinology , vegf receptors , biochemistry
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.