Wasielewska Joanna M., Da Silva Chaves Juliana C, White Anthony R., Oikari Lotta E.
Mental Health Program, Cell and Molecular Biology Department, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia
The blood–brain barrier is a semipermeable barrier structure that lines the walls of brain microvessels. Although the blood–brain barrier plays a key role in protecting the brain from unwanted molecules, it simultaneously challenges the delivery of drugs into the brain. In addition, the blood–brain barrier has been shown to be dysfunctional in Alzheimer’s disease, the most common cause of dementia for which there is no cure. Mouse models of Alzheimer’s disease have played a central role in investigating disease-specific changes in the blood–brain barrier, but the translation of findings from mouse models into the human system is hindered by interspecies differences. In an effort to develop new drug delivery techniques and/or understand changes in the human blood–brain barrier in Alzheimer’s disease, several human blood–brain barrier models have been developed. These comprise primary and immortalized human endothelial cell-based models as well as human induced pluripotent stem cell-derived brain microvascular endothelial cell models. Both two- and three-dimensional (2D and 3D) culture platforms have been established to better mimic the complexity of the brain. This chapter discusses the current blood–brain barrier models, their advantages and disadvantages as well as their potential to understand drug delivery in Alzheimer’s disease.
血脑屏障是一种半透性屏障结构，衬于脑微血管壁。尽管血脑屏障在保护大脑免受有害分子侵害方面发挥着关键作用，但它同时也给药物进入大脑带来了挑战。此外，血脑屏障在阿尔茨海默病（最常见的痴呆症病因且尚无治愈方法）中已被证明功能失调。阿尔茨海默病的小鼠模型在研究血脑屏障中疾病特异性变化方面发挥了核心作用，但由于种间差异，将小鼠模型的研究结果转化到人类系统中受到了阻碍。为了开发新的药物递送技术和/或了解阿尔茨海默病中人类血脑屏障的变化，已经开发了几种人类血脑屏障模型。这些模型包括基于原代和永生化人类内皮细胞的模型以及人类诱导多能干细胞衍生的脑微血管内皮细胞模型。已经建立了二维和三维（2D和3D）培养平台，以更好地模拟大脑的复杂性。本章讨论了当前的血脑屏障模型、它们的优缺点以及它们在理解阿尔茨海默病中药物递送方面的潜力。
