Institute of Neurology (Edinger Institute), University Hospital, Goethe University Frankfurt, Frankfurt am Main, Germany.
Excellence Cluster Cardio Pulmonary System (CPI), Partner Site Frankfurt, Frankfurt, Germany.
Handb Exp Pharmacol. 2022;273:3-31. doi: 10.1007/164_2020_404.
The blood-brain barrier (BBB) protects the vertebrate central nervous system from harmful blood-borne, endogenous and exogenous substances to ensure proper neuronal function. The BBB describes a function that is established by endothelial cells of CNS vessels in conjunction with pericytes, astrocytes, neurons and microglia, together forming the neurovascular unit (NVU). Endothelial barrier function is crucially induced and maintained by the Wnt/β-catenin pathway and requires intact NVU for proper functionality. The BBB and the NVU are characterized by a specialized assortment of molecular specializations, providing the basis for tightening, transport and immune response functionality.The present chapter introduces state-of-the-art knowledge of BBB structure and function and highlights current research topics, aiming to understanding in more depth the cellular and molecular interactions at the NVU, determining functionality of the BBB in health and disease, and providing novel potential targets for therapeutic BBB modulation. Moreover, we highlight recent advances in understanding BBB and NVU heterogeneity within the CNS as well as their contribution to CNS physiology, such as neurovascular coupling, and pathophysiology, is discussed. Finally, we give an outlook onto new avenues of BBB research.
血脑屏障(BBB)保护脊椎动物中枢神经系统免受有害的血源性、内源性和外源性物质的侵害,以确保神经元的正常功能。BBB 描述了一种由中枢神经系统血管内皮细胞与周细胞、星形胶质细胞、神经元和小胶质细胞共同形成的神经血管单元(NVU)所建立的功能。内皮屏障功能是由 Wnt/β-catenin 通路严格诱导和维持的,需要完整的 NVU 才能发挥正常功能。BBB 和 NVU 的特点是具有专门的分子特化,为紧密连接、转运和免疫反应功能提供了基础。本章介绍了 BBB 结构和功能的最新知识,并强调了当前的研究课题,旨在更深入地了解 NVU 的细胞和分子相互作用,确定 BBB 在健康和疾病中的功能,并为治疗性 BBB 调节提供新的潜在靶点。此外,我们强调了最近在理解中枢神经系统内的 BBB 和 NVU 异质性及其对中枢神经系统生理学(如神经血管耦联)和病理生理学的贡献方面的进展。最后,我们展望了 BBB 研究的新途径。