Tóth Andrea, Veszelka Szilvia, Nakagawa Shinsuke, Niwa Masami, Deli Mária A
Laboratory of Molecular Neurobiology, Institute of Biophysics, Biological Research Centre of the Hungarian Academy of Sciences, Szeged, Hungary.
Recent Pat CNS Drug Discov. 2011 May 1;6(2):107-18. doi: 10.2174/157488911795933910.
The blood-brain barrier (BBB) is a regulatory interface between the circulation and the central nervous system (CNS). Therapy of neurological diseases is limited due to restricted penetration of pharmacons across the BBB. Models for screening the brain penetration of drug candidates are needed early in drug discovery. Culture-based models are useful tools for both basic research on BBB, and testing the permeability of new therapeutical molecules. This review focuses on patented in vitro BBB models and their potential application in CNS drug discovery. Cell culture models using primary and immortalized brain endothelial cells of non-human and human origin, in co-culture or mono-culture setting, in static or dynamic conditions are discussed, as well as methods to induce BBB properties in such in vitro models. The aim of these models is to reproduce as many aspects as possible of the in vivo BBB. All models should show some elements of general endothelial and specific BBB properties, like physiologically realistic cell architecture, restrictive paracellular pathway, and functional expression of transport mechanisms. Though no "ideal in vitro BBB model" has been constructed yet, the currently available models provide valuable information on BBB permeability and are useful tools in CNS drug discovery.
血脑屏障（BBB）是循环系统与中枢神经系统（CNS）之间的调节界面。由于药物通过血脑屏障的渗透性受限，神经系统疾病的治疗受到限制。在药物研发早期就需要用于筛选候选药物脑渗透性的模型。基于细胞培养的模型对于血脑屏障的基础研究以及测试新治疗分子的渗透性都是有用的工具。本综述聚焦于已获专利的体外血脑屏障模型及其在中枢神经系统药物研发中的潜在应用。讨论了使用源自非人类和人类的原代及永生化脑内皮细胞的细胞培养模型，这些模型采用共培养或单培养方式，处于静态或动态条件下，还讨论了在这类体外模型中诱导血脑屏障特性的方法。这些模型的目的是尽可能多地重现体内血脑屏障的各个方面。所有模型都应展现出一些一般内皮细胞特性和特定血脑屏障特性的要素，比如生理上逼真的细胞结构、限制性细胞旁途径以及转运机制的功能性表达。尽管尚未构建出“理想的体外血脑屏障模型”，但目前可用的模型提供了有关血脑屏障渗透性的有价值信息，并且是中枢神经系统药物研发中的有用工具。
