@article{oai:nagasaki-u.repo.nii.ac.jp:00005522,
 author = {Takeshita, Tomonori and Nakagawa, Shinsuke and Tatsumi, Rie and So, Gohei and Hayashi, Kentaro and Tanaka, Kunihiko and Deli, Maria A. and Nagata, Izumi and Niwa, Masami},
 journal = {Molecular and Cellular Neuroscience},
 month = {May},
 note = {We investigated the effects of cilostazol, a selective inhibitor of phosphodiesterase 3, on blood-brain barrier (BBB) integrity against ischemia-reperfusion injury enhanced by advanced glycation endproducts (AGEs). We used in vitro BBB models with primarily cultured BBB-related cells from rats (brain capillary endothelial cells, astrocytes and pericytes), and subjected cells to either normoxia or 3-h oxygen glucose deprivation (OGD)/24-h reoxygenation with or without AGEs. Treatment of AGEs did not affect the transendothelial electrical resistance (TEER) in the BBB model under normoxia, but there was a significant decrease in TEER under 3-h OGD/24-h reoxygenation conditions with AGEs. Cilostazol inhibited decreases in TEER induced by 3-h OGD/24-h reoxygenation with AGEs. Immunocytochemical and Western blot analyses showed that AGEs reduced the expression of claudin-5, the main functional protein of tight junctions (TJs). In contrast, cilostazol increased the expression of claudin-5 under 3-h OGD/24-h reoxygenation with AGEs. Furthermore, while AGEs increased the production of extracellular transforming growth factor (TGF)-β1, cilostazol inhibited the production of extracellular TGF-β1 and restored the integrity of TJs. Thus, we found that AGEs enhanced ischemia-reperfusion injury, which mainly included decreases in the expression of proteins comprising TJs through the production of TGF-β1. Cilostazol appeared to limit ischemia-reperfusion injury with AGEs by improving the TJ proteins and inhibiting TGF-β1 signaling., Molecular and Cellular Neuroscience, 60, pp.1-9; 2014},
 pages = {1--9},
 title = {Cilostazol attenuates ischemia?reperfusion-induced blood?brain barrier dysfunction enhanced by advanced glycation endproducts via transforming growth factor-β1 signaling},
 volume = {60},
 year = {2014}
}