The blood-brain barrier: an engineering perspective.

Andrew D Wong, Mao Ye, Amanda F Levy, Jeffrey D Rothstein, Dwight E Bergles, Peter C Searson
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Abstract

It has been more than 100 years since Paul Ehrlich reported that various water-soluble dyes injected into the circulation did not enter the brain. Since Ehrlich's first experiments, only a small number of molecules, such as alcohol and caffeine have been found to cross the blood-brain barrier, and this selective permeability remains the major roadblock to treatment of many central nervous system diseases. At the same time, many central nervous system diseases are associated with disruption of the blood-brain barrier that can lead to changes in permeability, modulation of immune cell transport, and trafficking of pathogens into the brain. Therefore, advances in our understanding of the structure and function of the blood-brain barrier are key to developing effective treatments for a wide range of central nervous system diseases. Over the past 10 years it has become recognized that the blood-brain barrier is a complex, dynamic system that involves biomechanical and biochemical signaling between the vascular system and the brain. Here we reconstruct the structure, function, and transport properties of the blood-brain barrier from an engineering perspective. New insight into the physics of the blood-brain barrier could ultimately lead to clinical advances in the treatment of central nervous system diseases.

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血脑屏障:工程学视角。
自从保罗-埃利希(Paul Ehrlich)报告说,注入血液循环的各种水溶性染料无法进入大脑以来,已经过去了 100 多年。自艾里希首次实验以来,人们只发现酒精和咖啡因等少数分子能穿过血脑屏障,这种选择性渗透性仍然是治疗许多中枢神经系统疾病的主要障碍。与此同时,许多中枢神经系统疾病都与血脑屏障的破坏有关,血脑屏障的破坏会导致渗透性的改变、免疫细胞转运的调节以及病原体向大脑的贩运。因此,进一步了解血脑屏障的结构和功能是开发有效治疗各种中枢神经系统疾病的关键。过去 10 年中,人们逐渐认识到血脑屏障是一个复杂的动态系统,涉及血管系统和大脑之间的生物力学和生物化学信号传递。在这里,我们从工程学的角度重建了血脑屏障的结构、功能和传输特性。对血脑屏障物理学的新认识最终会促进中枢神经系统疾病的临床治疗。
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