Chan Gary N Y, Cannon Ronald E
National Institutes of Health, National Institute of Environmental Health Sciences, Intracellular Regulatory Group, Signal Transduction Laboratory, Research Triangle Park, North Carolina, USA.
Curr Protoc Pharmacol. 2017 Mar 17;76:7.16.1-7.16.16. doi: 10.1002/cpph.21.
The blood-brain barrier plays an important role in neuroprotection; however, it can be a major obstacle for drug delivery to the brain. This barrier primarily resides in the brain capillaries and functions as an interface between the brain and peripheral blood circulation. Several anatomical and biochemical elements of the blood-brain barrier are essential to regulate the permeability of nutrients, ions, hormones, toxic metabolites, and xenobiotics into and out of the brain. In particular, high expression of ATP-driven efflux transporters at the blood-brain barrier is a major obstacle in the delivery of CNS pharmacotherapeutics to the brain. The complete understanding of these elements can offer insights on how to modulate barrier functions for neuroprotection against CNS drug toxicity and to enhance drug delivery to the brain. In the literature, preclinical models of the blood-brain barrier are widely utilized to predict drug pharmacokinetics and pharmacodynamics properties in the brain. In addition, these models are essential tools to investigate cellular mechanisms and novel interventions that alter barrier function and permeability. This unit presents procedures to isolate fresh and viable rodent brain capillaries for the assessment of ex vivo transport activity at the blood-brain barrier. © 2017 by John Wiley & Sons, Inc.
血脑屏障在神经保护中发挥着重要作用；然而，它可能成为药物输送到大脑的主要障碍。该屏障主要存在于脑毛细血管中，作为大脑与外周血液循环之间的界面发挥作用。血脑屏障的几个解剖学和生物化学要素对于调节营养物质、离子、激素、有毒代谢产物和外源性物质进出大脑的通透性至关重要。特别是，血脑屏障处ATP驱动的外排转运体的高表达是中枢神经系统药物治疗剂输送到大脑的主要障碍。对这些要素的全面理解可以为如何调节屏障功能以保护中枢神经系统免受药物毒性以及增强药物向大脑的输送提供见解。在文献中，血脑屏障的临床前模型被广泛用于预测药物在大脑中的药代动力学和药效学特性。此外，这些模型是研究改变屏障功能和通透性的细胞机制及新型干预措施的重要工具。本单元介绍了分离新鲜且有活力的啮齿动物脑毛细血管以评估血脑屏障体外转运活性的方法。© 2017约翰威立父子出版公司。
