Erythropoietin protects the in vitro blood–brain barrier against VEGF‐induced permeability
Abstract
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.
Part of CIRS biomarkers research · Curated by Lauren Lowenstein, The Biotoxin Lady
Key Biomarkers
Cited By (10)
- Erythropoietin as an antiapoptotic, tissue-protective cytokineCell Death and Differentiation · 2004
- Erythropoietin Is Neuroprotective in a Preterm Ovine Model of Endotoxin-Induced Brain InjuryJournal of Neuropathology & Experimental Neurology · 2010
- The potential role of vascular endothelial growth factor in the central nervous systemReviews in the Neurosciences · 2004
- Brain endothelial cells and the glio-vascular complexCell and Tissue Research · 2009
- New avenues of exploration for erythropoietinJAMA · 2005
- Erythropoietin in the brain: can the promise to protect be fulfilled?Trends in Pharmacological Sciences · 2004
- Erythropoietin ameliorates damage to the placenta and fetal liver induced by exposure to lipopolysaccharidePlacenta · 2010
- The brain erythropoietin system and its potential for therapeutic exploitation in brain diseaseJournal of Neurosurgical Anesthesiology · 2006
- Erythropoietin protects dopaminergic neurons and improves neurobehavioral outcomes in juvenile rats after neonatal hypoxia-ischemiaPediatric Research · 2005
- Erythropoietin on a tightrope: balancing neuronal and vascular protection between intrinsic and extrinsic pathwaysNeurosignals · 2004
References (4)
- Erythropoietin protects neurons against chemical hypoxia and cerebral ischemic injury by up‐regulating Bcl‐xL expressionJournal of Neuroscience Research · 2002
- Erythropoietin crosses the blood-brain barrier to protect against experimental brain injuryProceedings of the National Academy of Sciences · 2000
- Erythropoietin is a novel vascular protectant through activation of Akt1 and mitochondrial modulation of cysteine proteasesCirculation · 2002
- Erythropoietin receptor-mediated inhibition of exocytotic glutamate release confers neuroprotection during chemical ischemiaJournal of Biological Chemistry · 2001
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