Department of Pharmacology, The University of Melbourne, Australia.
Mol Aspects Med. 2013 Apr-Jun;34(2-3):742-52. doi: 10.1016/j.mam.2012.11.006.
The protective barriers of the brain provide a complex series of physical and chemical obstacles to movement of macromolecules from the periphery into the central nervous system. Studies on these barriers have been focused on two main research areas: (i) anatomical and physiological descriptions of their properties, including during development where functioning barriers are likely to be important for normal neuronal growth; and (ii), investigations of these barriers during disease and attempts at overcoming their defenses in order to deliver drugs to the central nervous system. Both fields are now advanced by the application of molecular gene expression studies of cerebral endothelia (blood vasculature, site of the blood-brain barrier) and choroid plexus epithelia (site of the blood-cerebrospinal fluid barrier) from developing and adult brains, particularly with respect to solute-linked carriers and other transporters. These new techniques provide a wealth of information on the changing nature of transporters at barrier interfaces during normal development and following disease. This review outlines published findings from transcriptome and qPCR studies of expression of genes coding for transporters in these barriers, with a focus on developing brain. The findings clearly support earlier published physiological data describing specific transport mechanisms across barrier interfaces both in the adult and in particular in the developing brain.
大脑的保护屏障为大分子从外周进入中枢神经系统提供了一系列复杂的物理和化学障碍。这些屏障的研究集中在两个主要研究领域:(i) 对其特性的解剖学和生理学描述,包括在可能对正常神经元生长很重要的发育过程中;以及 (ii),在疾病期间对这些屏障的研究以及试图克服它们的防御以将药物递送到中枢神经系统。这两个领域都得益于对来自发育中和成年大脑的脑内皮(血管系统,血脑屏障的部位)和脉络丛上皮(血脑脊液屏障的部位)的分子基因表达研究的应用得到了推进,特别是涉及溶质相关载体和其他转运体。这些新技术提供了大量关于正常发育和疾病后屏障界面上转运体性质变化的信息。本综述概述了关于这些屏障中转运体基因表达的转录组和 qPCR 研究的已发表发现,重点是发育中的大脑。这些发现清楚地支持了更早发表的生理学数据,描述了在成人特别是在发育中的大脑中穿过屏障界面的特定转运机制。