Förster, C.; Burek, M.; Romero, I. A.; Weksler, B.; Couraud, P. O. and Drenckhahn, D.
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|DOI (Digital Object Identifier) Link:||http://doi.org/10.1113/jphysiol.2007.146852|
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Homeostasis of the central nervous system (CNS) microenvironment is maintained by the blood-brain barrier (BBB) which regulates the transport of molecules from blood into brain and back. Many disorders change the functionality and integrity of the BBB. Glucocorticoids are being used sucessfully in the treatment of some disorders while their effects on others are questionable. In addition, conflicting results between clinical and experimental experience using animal models has arisen, so that the results of molecular studies in animal models need to be revisited in an appropriate in vitro model of the human BBB for more effective treatment strategies. Using the human brain microvascular endothelial cell line hCMEC/D3, the influence of glucocorticoids on the expression of barrier constituting adherens junction and tight junction transmembrane proteins (VE-cadherin, occludin, claudins) was investigated and compared to other established BBB models. In hCMEC/D3 cells the administration of glucocorticoids induced expression of the targets occludin 2.75 +/- 0.04-fold and claudin-5 up to 2.32 +/- 0.11-fold, which is likely to contribute to the more than threefold enhancement of transendothelial electrical resistance reflecting barrier tightness. Our analyses further provide direct evidence that the GC hydrocortisone prevents endothelial barrier breakdown in response to pro-inflammatory stimuli (TNFalpha administration), which could be demonstrated to be partly based on maintenance of occludin levels. Our studies strongly suggest stabilization of BBB function as a mode of GC action on a molecular level in the human brain vasculature.
|Item Type:||Journal Article|
|Academic Unit/Department:||Science > Life, Health and Chemical Sciences
|Interdisciplinary Research Centre:||Biomedical Research Network (BRN)|
|Depositing User:||Ignacio A Romero|
|Date Deposited:||30 Apr 2008|
|Last Modified:||25 Feb 2016 10:42|
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