Obermeier Birgit, Verma Ajay, Ransohoff Richard M
Neuro/Immuno Discovery Biology, Biogen, Cambridge, MA, USA.
Biomarkers and Experimental Medicine, Biogen, Cambridge, MA, USA.
Handb Clin Neurol. 2016;133:39-59. doi: 10.1016/B978-0-444-63432-0.00003-7.
In autoimmune neurologic disorders, the blood-brain barrier (BBB) plays a central role in immunopathogenesis, since this vascular interface is an entry path for cells and effector molecules of the peripheral immune system to reach the target organ, the central nervous system (CNS). The BBB's unique anatomic structure and the tightly regulated interplay of its cellular and acellular components allow for maintenance of brain homeostasis, regulation of influx and efflux, and protection from harm; these ensure an optimal environment for the neuronal network to function properly. In both health and disease, the BBB acts as mediator between the periphery and the CNS. For example, immune cell trafficking through the cerebral vasculature is essential to clear microbes or cell debris from neural tissues, while poorly regulated cellular transmigration can underlie or worsen CNS pathology. In this chapter, we focus on the specialized multicellular structure and function of the BBB/neurovascular unit and discuss how BBB breakdown can precede or be a consequence of neuroinflammation. We introduce the blood-cerebrospinal fluid barrier and include a brief aside about evolutionary aspects of barrier formation and refinements. Lastly, since restoration of barrier function is considered key to ameliorate neurologic disease, we speculate about new therapeutic avenues to repair a damaged BBB.
在自身免疫性神经疾病中，血脑屏障（BBB）在免疫发病机制中起核心作用，因为这个血管界面是外周免疫系统的细胞和效应分子到达靶器官——中枢神经系统（CNS）的一条进入途径。血脑屏障独特的解剖结构及其细胞和非细胞成分之间严格调控的相互作用，有助于维持脑内稳态、调节物质的流入和流出，并保护大脑免受伤害；这些确保了神经网络正常运作的最佳环境。在健康和疾病状态下，血脑屏障都充当着外周和中枢神经系统之间的介质。例如，免疫细胞通过脑血管系统的运输对于清除神经组织中的微生物或细胞碎片至关重要，而细胞迁移调节不当可能是中枢神经系统病理学的基础或使其恶化。在本章中，我们重点关注血脑屏障/神经血管单元的特殊多细胞结构和功能，并讨论血脑屏障破坏如何先于神经炎症或作为神经炎症的结果。我们介绍血脑脊液屏障，并简要提及屏障形成和完善的进化方面。最后，由于恢复屏障功能被认为是改善神经疾病的关键，我们推测修复受损血脑屏障的新治疗途径。
