期刊
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
卷 31, 期 2, 页码 767-777出版社
SAGE PUBLICATIONS INC
DOI: 10.1038/jcbfm.2010.162
关键词
atherosclerosis; alternative; cerebral blood flow; inflammation; in vitro; ischemia; shear stress; white blood cells
资金
- Alternative Research Development Foundation (ARDF)
- [NIH-2RO1 HL51614]
- [NIH-RO1 NS43284]
- [NIH-RO1 NS38195]
Although there is significant evidence correlating overreacting or perhaps misguided immune cells and the blood-brain barrier (BBB) with the pathogenesis of neuroinflammatory diseases, the mechanisms by which they enter the brain are largely unknown. For this purpose, we revised our humanized dynamic in vitro BBB model (DIV-BBBr) to incorporate modified hollow fibers that now feature transmural microholes (2 to 4 mu m empty set) allowing for the transendothelial trafficking of immune cells. As with the original model, this new DIV-BBBr reproduces most of the physiological characteristics of the BBB in vivo. Measurements of transendothelial electrical resistance (TEER), sucrose permeability, and BBB integrity during reversible osmotic disruption with mannitol (1.6 mol/L) showed that the microholes do not hamper the formation of a tight functional barrier. The in vivo rank permeability order of sucrose, phenytoin, and diazepam was successfully reproduced in vitro. Flow cessation followed by reperfusion (Fc/Rp) in the presence of circulating monocytes caused a biphasic BBB opening paralleled by a significant increase of proinflammatory cytokines and activated matrix metalloproteinases. We also observed abluminal extravasation of monocytes but only when the BBB was breached. In conclusion, the DIV-BBBr represents the most realistic in vitro system to study the immune cell trafficking across the BBB. Journal of Cerebral Blood Flow & Metabolism (2011) 31, 767-777; doi:10.1038/jcbfm.2010.162; published online 15 September 2010
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据