Berthiaume Andrée-Anne, Hartmann David A, Majesky Mark W, Bhat Narayan R, Shih Andy Y
Department of Neuroscience, Medical University of South Carolina, Charleston, SC, United States.
Center for Developmental Biology and Regenerative Medicine, Seattle Children's Research Institute, Seattle, WA, United States.
Front Aging Neurosci. 2018 Jul 17;10:210. doi: 10.3389/fnagi.2018.00210. eCollection 2018.
The biology of brain microvascular pericytes is an active area of research and discovery, as their interaction with the endothelium is critical for multiple aspects of cerebrovascular function. There is growing evidence that pericyte loss or dysfunction is involved in the pathogenesis of Alzheimer's disease, vascular dementia, ischemic stroke and brain injury. However, strategies to mitigate or compensate for this loss remain limited. In this review, we highlight a novel finding that pericytes in the adult brain are structurally dynamic , and actively compensate for loss of endothelial coverage by extending their far-reaching processes to maintain contact with regions of exposed endothelium. Structural remodeling of pericytes may present an opportunity to foster pericyte-endothelial communication in the adult brain and should be explored as a potential means to counteract pericyte loss in dementia and cerebrovascular disease. We discuss the pathophysiological consequences of pericyte loss on capillary function, and the biochemical pathways that may control pericyte remodeling. We also offer guidance for observing pericytes , such that pericyte structural remodeling can be more broadly studied in mouse models of cerebrovascular disease.
脑微血管周细胞的生物学是一个活跃的研究和发现领域,因为它们与内皮细胞的相互作用对脑血管功能的多个方面至关重要。越来越多的证据表明,周细胞丢失或功能障碍与阿尔茨海默病、血管性痴呆、缺血性中风和脑损伤的发病机制有关。然而,减轻或补偿这种损失的策略仍然有限。在这篇综述中,我们强调了一项新发现,即成年大脑中的周细胞在结构上是动态的,并通过延伸其深远的突起以维持与暴露的内皮区域的接触,积极补偿内皮覆盖的损失。周细胞的结构重塑可能为促进成年大脑中的周细胞 - 内皮细胞通讯提供机会,应作为抵消痴呆和脑血管疾病中周细胞损失的潜在手段进行探索。我们讨论了周细胞损失对毛细血管功能的病理生理后果,以及可能控制周细胞重塑的生化途径。我们还提供了观察周细胞的指导,以便在脑血管疾病的小鼠模型中更广泛地研究周细胞结构重塑。