Neuropsychopharmacologie des addictions (CNRS UMR 8206), Université Paris Descartes, Faculté de Pharmacie, Paris, France.
Curr Drug Metab. 2013 Jan;14(1):120-36.
The penetration of drugs into the human brain through the blood-brain barrier (BBB) is a major obstacle limiting the development of successful neuropharmaceuticals. This restricted permeability is due to the delicate intercellular junctions, efflux transporters and metabolizing enzymes present at the BBB. The pharmaceutical industry and academic research relies heavily on permeability studies conducted in animals and in vitro models of the BBB. This text reviews the available animal and in vitro BBB models with special emphasis on the situation in freshly isolated human brain microvessels and the unique tightness between brain endothelial cells, drug transport pathways and metabolic capacity. We first outline the delicate structure of the intercellular junctions and the particular interaction between the brain endothelial cells and other components of the neurovascular unit. We then examine the differences in transporters and metabolizing enzymes between species and in vitro systems and those found in isolated brain microvessels. Finally, we review the possibilities of benchmarking in vitro models of the BBB in terms of gene and protein expression.
药物通过血脑屏障（BBB）进入人脑是限制神经药物成功开发的主要障碍。这种有限的通透性是由于 BBB 存在精细的细胞间连接、外排转运体和代谢酶。制药行业和学术研究严重依赖于在动物和 BBB 的体外模型中进行的通透性研究。本文综述了现有的动物和体外 BBB 模型，特别强调了新鲜分离的人脑微血管和脑内皮细胞之间独特的紧密性、药物转运途径和代谢能力的情况。我们首先概述了细胞间连接的精细结构以及脑内皮细胞与神经血管单元其他成分之间的特殊相互作用。然后，我们研究了物种和体外系统之间以及在分离的脑微血管中发现的转运体和代谢酶的差异。最后，我们回顾了基于基因和蛋白质表达对 BBB 体外模型进行基准测试的可能性。
