title: Vitamin D prevents hypoxia/reoxygenation-induced blood-brain barrier disruption via vitamin D receptor-mediated NF-kB signaling pathways.
abstract: Maintaining blood-brain barrier integrity and minimizing neuronal injury are critical components of any therapeutic intervention following ischemic stroke. However, a low level of vitamin D hormone is a risk factor for many vascular diseases including stroke. The neuroprotective effects of 1,25(OH)2D3 (vitamin D) after ischemic stroke have been studied, but it is not known whether it prevents ischemic injury to brain endothelial cells, a key component of the neurovascular unit. We analyzed the effect of 1,25(OH)2D3 on brain endothelial cell barrier integrity and tight junction proteins after hypoxia/reoxygenation in a mouse brain endothelial cell culture model that closely mimics many of the features of the blood-brain barrier in vitro. Following hypoxic injury in bEnd.3 cells, 1,25(OH)2D3 treatment prevented the decrease in barrier function as measured by transendothelial electrical resistance and permeability of FITC-dextran (40 kDa), the decrease in the expression of the tight junction proteins zonula occludin-1, claudin-5, and occludin, the activation of NF-kB, and the increase in matrix metalloproteinase-9 expression. These responses were blocked when the interaction of 1,25(OH) )2D3 with the vitamin D receptor (VDR) was inhibited by pyridoxal 5'-phosphate treatment. Our findings show a direct, VDR-mediated, protective effect of 1,25(OH) )2D3 against ischemic injury-induced blood-brain barrier dysfunction in cerebral endothelial cells.
authors: Department of Emergency Medicine Brain Research Laboratory, Emory University, Atlanta, Georgia, United States of America.
authors: Soonmi
authors: S
authors: Won
authors: Department of Emergency Medicine Brain Research Laboratory, Emory University, Atlanta, Georgia, United States of America.
authors: Iqbal
authors: I
authors: Sayeed
authors: Department of Emergency Medicine Brain Research Laboratory, Emory University, Atlanta, Georgia, United States of America.
authors: Bethany L
authors: BL
authors: Peterson
authors: Department of Emergency Medicine Brain Research Laboratory, Emory University, Atlanta, Georgia, United States of America.
authors: Bushra
authors: B
authors: Wali
authors: Department of Emergency Medicine Brain Research Laboratory, Emory University, Atlanta, Georgia, United States of America.
authors: Jared S
authors: JS
authors: Kahn
authors: Department of Emergency Medicine Brain Research Laboratory, Emory University, Atlanta, Georgia, United States of America.
authors: Donald G
authors: DG
authors: Stein
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects; D001930:Brain Injuries; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D015687:Cell Hypoxia / Q000187:drug effects; D042783:Endothelial Cells / Q000187:drug effects / Q000473:pathology; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000473:pathology; D016328:NF-kappa B / Q000378:metabolism; D018167:Receptors, Calcitriol / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D020521:Stroke / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D014807:Vitamin D / Q000008:administration & dosage*
chemical_list: D016328:NF-kappa B; D018167:Receptors, Calcitriol; D014807:Vitamin D