Cilostazol inhibits the redistribution of the actin cytoskeleton and junctional proteins on the blood-brain barrier under hypoxia/reoxygenation

Cilostazol is a selective inhibitor of cyclic nucleotide phosphodiesterase 3 (PDE3), which induces a vasodilatoric antiplatelet effect. In the present study, we investigated the impact of cilostazol on the blood-brain barrier (BBB), while focusing on the actin cytoskeleton (F-actin), the permeability of endothelial cells, and the junctional proteins under hypoxia/reoxygenation (H/R). Cilostazol was thus found to inhibit the cytoskeletal reorganization under H/R, in which F-actin decrease at the cell periphery. Accordingly, cilostazol was able to attenuate the hyperpermeability of endothelial cells in H/R to the level of the permeability in normoxia. However, the adherens junction (AJ) protein VE-cadherin was not preserved in the presence of cilostazol under H/R. On the other hand, beta-catenin was slightly retained by cilostazol. In contrast to the redistribution of these proteins, immunoblotting demonstrated the total amount of AJ and tight junction (TJ) proteins (occludin, ZO-1 and ZO-2) to not show any significant change under H/R stress in either the presence or absence of cilostazol. Taken together, cilostazol potently displayed a protective effect against acute ischemia by preventing an increase in the endothelial permeability through the preservation of the actin cytoskeleton and the redistribution of junctional proteins. (c) 2006 Published by Elsevier Ltd.