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）是大脑微血管内的连续内皮膜，它密封了细胞与细胞的接触，并被壁血管细胞和血管周围星形胶质细胞端脚包裹。BBB 保护神经元免受体循环中存在的因素的影响，并维持高度调节的 CNS 内部环境，这是正常突触和神经元功能所必需的。血脑屏障破坏使得神经毒性血液碎片、细胞和微生物病原体流入大脑，并与炎症和免疫反应相关，从而引发多种神经退行性病变途径。这篇综述讨论了活人大脑和死后组织的神经影像学研究，以及证明阿尔茨海默病、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血脑屏障破坏的生物标志物研究。描述了血脑屏障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变性的致病机制。简要讨论了健康 BBB 对于治疗药物输送的重要性以及疾病引发的病理性 BBB 破坏与神经药物脑输送相关的不利影响。最后，提出了未来的方向、该领域的差距以及通过针对 BBB 来控制神经系统疾病进程的机会。