Abstract

The effect of lipopolysaccharide (LPS) on cultured cerebral endothelial cells was investigated to assess the changes in the trans endothelial electrical resistance (TEER) across the blood-brain barrier that may occur during inflammatory diseases of the central nervous system. Primary cultures of bovine cerebral endothelial cells were cultured to tight monolayers with a TEER of 250 to 300 omega.cm2 on polycarbonate Transwell filters. LPS induced a time- and dose-dependent decline in TEER. Transport of the hydrophilic model compounds sodium fluorescein and fluorescein dextran (MR, 4 kDa) across monolayers of bovine cerebral endothelial cells increased more than 3-fold after treatment of the cells with LPS (50 ng/ml). Treatment of the monolayers with various concentrations of LPS caused a 3-to 4-fold increase in the permeability of bovine cerebral endothelial cells for [125I]bovine serum albumin, which was also preceded by a decrease in TEER. The reduction of TEER by LPS could be inhibited completely by indomethacin (10(-6)M for 30 min), a cyclooxygenase inhibitor, but not by dexamethasone, a glucocorticoid (10(-7) M for 16 hr). In conclusion, LPS administration to blood-brain barrier endothelial cells causes a decrease in TEER which leads to enhanced transport of low and high molecular weight molecules. During this process the production of eicosanoids by the endothelial cells seem to play a key role.