Blood-brain barrier breakdown in Alzheimer disease and other neurodegenerative disorders.
Blood-brain barrier breakdown in Alzheimer disease and other neurodegenerative disorders.
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DOI：
10.1038/nrneurol.2017.188
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发表时间：
2018-03
期刊：
影响因子：
--
通讯作者：
Zlokovic BV
中科院分区：
文献类型：
--
作者：
Sweeney MD;Sagare AP;Zlokovic BV
血脑屏障（BBB）是脑微血管内的连续内皮膜，其具有密封的细胞与细胞接触，并且被壁血管细胞和血管周围星形胶质细胞端足覆盖。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，这是适当的突触和神经元功能所需的。BBB破坏允许神经毒性血液来源的碎片、细胞和微生物病原体流入大脑，并且与炎症和免疫反应相关，这可以启动神经变性的多种途径。本综述讨论了活体人脑的神经影像学研究、死后组织和生物标志物研究，这些研究证明了阿尔茨海默病、帕金森病、亨廷顿病、肌萎缩侧索硬化症、多发性硬化症、HIV-1相关性痴呆和慢性创伤性脑病中的BBB崩溃。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变性的致病机制。一个健康的血脑屏障的治疗药物输送的重要性，以及疾病引发的不良影响，病理性血脑屏障崩溃有关的脑神经药物的交付进行了简要讨论。最后，未来的方向，在该领域的差距和机会，以控制神经系统疾病的过程中，针对血脑屏障。
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, post-mortem tissue and 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 BBB are presented.
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