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Author Notes:

Email: isayeed@emory.edu

Conceived and designed the experiments: IS SW. Performed the experiments: SW JSK BW. Analyzed the data: IS SW BLP. Contributed reagents/materials/analysis tools: IS DGS. Wrote the paper: IS SW DGS.

There are no patents, products in development or marketed products to declare. This does not alter the authors adherence to all the PLOS ONE policies on sharing data and materials, as detailed online in the guide for authors.


Research Funding:

This study was partly funded by BHR Pharma

This work was supported by American Heart Association SDG grant 11SDG5430002 to IS and National Health Institute R01HD061971 to DGS. Partial funding for some of the assays used in this project was provided by the Marcus Foundation of Atlanta and BHR Pharma. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript


  • Science & Technology
  • Multidisciplinary Sciences
  • Science & Technology - Other Topics

Vitamin D Prevents Hypoxia/Reoxygenation-Induced Blood-Brain Barrier Disruption via Vitamin D Receptor-Mediated NF-kB Signaling Pathways

Journal Title:



Volume 10, Number 3


, Pages e0122821-e0122821

Type of Work:

Article | Final Publisher PDF


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.

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© 2015 Won et al

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