Department of Physiology and Neuroscience and the Zilkha Neurogenetic Institute, Keck School of Medicine of the University of Southern California, 1501 San Pablo Street, Los Angeles, California 90089, USA.
Nat Rev Neurol. 2018 Mar;14(3):133-150. doi: 10.1038/nrneurol.2017.188. Epub 2018 Jan 29.
The blood-brain barrier (BBB) is a continuous endothelial membrane within brain microvessels that has sealed cell-to-cell contacts and is sheathed by mural vascular cells and perivascular astrocyte end-feet. The BBB protects neurons from factors present in the systemic circulation and maintains the highly regulated CNS internal milieu, which is required for proper synaptic and neuronal functioning. BBB disruption allows influx into the brain of neurotoxic blood-derived debris, cells and microbial pathogens and is associated with inflammatory and immune responses, which can initiate multiple pathways of neurodegeneration. This Review discusses neuroimaging studies in the living human brain and post-mortem tissue as well as biomarker studies demonstrating BBB breakdown in Alzheimer disease, Parkinson disease, Huntington disease, amyotrophic lateral sclerosis, multiple sclerosis, HIV-1-associated dementia and chronic traumatic encephalopathy. The pathogenic mechanisms by which BBB breakdown leads to neuronal injury, synaptic dysfunction, loss of neuronal connectivity and neurodegeneration are described. The importance of a healthy BBB for therapeutic drug delivery and the adverse effects of disease-initiated, pathological BBB breakdown in relation to brain delivery of neuropharmaceuticals are briefly discussed. Finally, future directions, gaps in the field and opportunities to control the course of neurological diseases by targeting the BBB are presented.
血脑屏障（BBB）是脑微血管内的连续内皮膜，具有封闭的细胞间连接，由血管壁细胞和血管周星形胶质细胞终足包裹。BBB 保护神经元免受循环系统中存在的因素的影响，并维持高度调节的中枢神经系统内环境，这是适当的突触和神经元功能所必需的。BBB 破坏允许神经毒性血液衍生碎片、细胞和微生物病原体进入大脑，并与炎症和免疫反应有关，这些反应可以引发多种神经退行性变途径。这篇综述讨论了活体人脑和尸检组织中的神经影像学研究，以及生物标志物研究，这些研究表明阿尔茨海默病、帕金森病、亨廷顿病、肌萎缩侧索硬化症、多发性硬化症、HIV-1 相关痴呆和慢性创伤性脑病中存在 BBB 破坏。描述了 BBB 破坏导致神经元损伤、突触功能障碍、神经元连接丧失和神经退行性变的致病机制。还简要讨论了健康的 BBB 对治疗性药物输送的重要性，以及疾病引起的、与神经药物脑输送相关的病理性 BBB 破坏对大脑的不良影响。最后，提出了未来的方向、该领域的差距以及通过靶向 BBB 控制神经疾病进程的机会。
