Chavarria Daniel, Abbaspour Ali, Celestino Natalie, Shah Nehali, Sankar Sharanya, Baker Aaron B
Department of Biomedical Engineering, University of Texas at Austin, Austin, Texas 78712, USA.
Biomicrofluidics. 2023 Aug 21;17(4):044105. doi: 10.1063/5.0150887. eCollection 2023 Jul.
The blood-brain barrier is a key structure regulating the health of the brain and access of drugs and pathogens to neural tissue. Shear stress is a key regulator of the blood-brain barrier; however, the commonly used multi-well vitro models of the blood-brain barrier do not incorporate shear stress. In this work, we designed and validated a high-throughput system for simulating the blood-brain barrier that incorporates physiological flow and incorporates an optimized cellular model of the blood-brain barrier. This system can perform assays of blood-brain barrier function with shear stress, with 48 independent assays simultaneously. Using the high throughput assay, we conducted drug screening assays to explore the effects of compounds for opening or closing blood-brain barrier. Our studies revealed that assays with shear stress were more predictive and were able to identify compounds known to modify the blood-brain barrier function while static assays were not. Overall, we demonstrate an optimized, high throughput assay for simulating the blood-brain barrier that incorporates shear stress and is practical for use in drug screening and other high throughput studies of toxicology.
血脑屏障是调节大脑健康以及药物和病原体进入神经组织的关键结构。剪切应力是血脑屏障的关键调节因子；然而，常用的血脑屏障多孔体外模型并未纳入剪切应力。在这项工作中，我们设计并验证了一种用于模拟血脑屏障的高通量系统，该系统纳入了生理流动并采用了优化的血脑屏障细胞模型。该系统能够在有剪切应力的情况下进行血脑屏障功能测定，可同时进行48项独立测定。利用该高通量测定法，我们开展了药物筛选试验，以探究化合物对血脑屏障开放或关闭的影响。我们的研究表明，有剪切应力的测定更具预测性，能够识别已知可改变血脑屏障功能的化合物，而静态测定则无法做到。总体而言，我们展示了一种优化的、用于模拟血脑屏障的高通量测定法，该方法纳入了剪切应力，适用于药物筛选及其他毒理学高通量研究。
