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 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.
Martínez-Estrada
Ofelia María
OM
Departament de Biologia Cel.lular, Facultat Biologia, Universitat de Barcelona, E-08028 Barcelona, Spain. ofelia@porthos.bio.ub.es
Rodríguez-Millán
Elisabeth
E
González-De Vicente
Esther
E
Reina
Manuel
M
Vilaró
Senén
S
Fabre
Myriam
M
D000818:Animals; D001253:Astrocytes / Q000502:physiology; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology*; D015153:Blotting, Western; D001921:Brain / Q000502:physiology; D002199:Capillary Permeability / Q000187:drug effects* / Q000502:physiology; D002417:Cattle; D018920:Coculture Techniques; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D004921:Erythropoietin / Q000494:pharmacology / Q000502:physiology*; D005455:Fluorescent Antibody Technique; D018696:Neuroprotective Agents / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017467:Receptors, Erythropoietin / Q000378:metabolism / Q000502:physiology*; D019108:Tight Junctions / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*
D018696:Neuroprotective Agents; D017467:Receptors, Erythropoietin; D042461:Vascular Endothelial Growth Factor A; D004921:Erythropoietin; D019001:Nitric Oxide Synthase