Department of Pathology (A.V.A., A.F.C.-M., S.M.S.), University of Michigan Medical School, Ann Arbor.
Department of Neurosurgery (A.V.A., J.X., R.F.K.), University of Michigan Medical School, Ann Arbor.
Stroke. 2023 Mar;54(3):661-672. doi: 10.1161/STROKEAHA.122.040578. Epub 2023 Feb 27.
Cerebral endothelial cells and their linking tight junctions form a unique, dynamic and multi-functional interface, the blood-brain barrier (BBB). The endothelium is regulated by perivascular cells and components forming the neurovascular unit. This review examines BBB and neurovascular unit changes in normal aging and in neurodegenerative disorders, particularly focusing on Alzheimer disease, cerebral amyloid angiopathy and vascular dementia. Increasing evidence indicates BBB dysfunction contributes to neurodegeneration. Mechanisms underlying BBB dysfunction are outlined (endothelium and neurovascular unit mediated) as is the BBB as a therapeutic target including increasing the uptake of systemically delivered therapeutics across the BBB, enhancing clearance of potential neurotoxic compounds via the BBB, and preventing BBB dysfunction. Finally, a need for novel biomarkers of BBB dysfunction is addressed.
脑内皮细胞及其连接的紧密连接形成了一个独特的、动态的和多功能的界面，即血脑屏障（BBB）。内皮细胞受血管周围细胞和形成神经血管单元的成分调节。本综述检查了正常衰老和神经退行性疾病中 BBB 和神经血管单元的变化，特别是重点关注阿尔茨海默病、脑淀粉样血管病和血管性痴呆。越来越多的证据表明，BBB 功能障碍导致神经退行性变。本文概述了 BBB 功能障碍的潜在机制（涉及内皮细胞和神经血管单元），并探讨了 BBB 作为治疗靶点的可能性，包括增加全身给药治疗药物通过 BBB 的摄取、增强通过 BBB 清除潜在神经毒性化合物，以及预防 BBB 功能障碍。最后，还需要新的 BBB 功能障碍的生物标志物。
