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Pharmacological investigations on lipopolysaccharide-induced permeability changes in the blood-brain barrier in vitro

被引：59
作者：
Gaillard, PJ [1 ]
de Boer, AG [1 ]
Breimer, DD [1 ]
机构：
[1] Leiden Univ, Gorlaeus Labs, Dept Pharmacol, LACDR,Blood Brain Barrier Res Grp, NL-2300 RA Leiden, Netherlands
来源：
MICROVASCULAR RESEARCH | 2003年 / 65卷 / 01期
关键词：
blood-brain barrier; lipopolysaccharide; inflammation; brain capillary endothelial cells; brain astrocytes;
D O I：
10.1016/S0026-2862(02)00009-2
中图分类号：
R6 [外科学];
学科分类号：
1002 ; 100210 ;
摘要：
Lipopolysaccharide-induced changes in blood-brain barrier (BBB) permeability were investigated with a pharmacological approach in vitro. Lipopolysaccharide induced a concentration- and time-dependent (non)reversible opening of the BBB, and brain astrocytes make brain capillary endothelial cells (BCEC) resistant to this BBB disruption. De novo protein synthesis was essential for the recovery, because cycloheximide prevented the recovery process. Dexamethasone pretreated BCEC were more resistant to lipopolysaccharide, while no protective response was induced by heat shock nor by inhibition of P-glycoprotein. BBB opening was tempered by free radical inhibitors (i.e., pretreatment with N-acetyl-cysteine or uric acid combined with deferroxamine mesylate). No effects of modulators of prostanoid-, leukotriene-, or platelet-activating factor pathways were observed. Therefore, lipopolysaccharide-induced BBB opening seems to be primarily mediated by excessive free radical production. (C) 2003 Elsevier Science (USA). All rights reserved.
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页码：24 / 31
页数：8
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