血脑屏障
封堵器
体内
体外
紧密连接
细胞生物学
过剩1
免疫细胞化学
克洛丹
化学
污渍
生物
药理学
中枢神经系统
葡萄糖转运蛋白
生物化学
神经科学
生物技术
内分泌学
基因
胰岛素
作者
Gilda Shayan,Yong Seok Choi,Eric V. Shusta,Michael L. Shuler,Kelvin H. Lee
标识
DOI:10.1016/j.ejps.2010.11.005
摘要
In vitro blood–brain barrier (BBB) models help predict brain uptake of potential central nervous system drug candidates. Current in vitro models are composed of brain microvascular endothelial cells (BMEC) that are isolated from rat, bovine, or porcine. However, most in vivo studies on drug transport through the BBB are performed in small laboratory animals, specially mouse and thus murine in vitro BBB models serve as better surrogates to correlate with these studies. Here we describe the functional characterization of a reproducible in vitro model composed of murine BMEC co-cultured with rat primary astrocytes in the presence of biochemical inducing agents. The co-cultures presented high TEER and low sodium fluorescein permeability. Expression of specific BBB tight junction proteins (occludin, claudin-5, ZO-1) and the functionality of transporters (Pgp, GLUT1) were detected by immunocytochemistry and Western blotting. These results indicated a 2.5-fold increase in the expression levels of these proteins in the presence of astrocytes. In addition, a high correlation coefficient (0.98) was obtained between the permeability of a series of hydrophobic and hydrophilic drugs and their corresponding in vivo values. These results together establish the utility of this murine model for future drug transport, pathological, and pharmacological characterizations of the BBB.
科研通智能强力驱动
Strongly Powered by AbleSci AI