Shaw Kira, Boyd Katie, Anderle Silvia, Hammond-Haley Matthew, Amin Davina, Bonnar Orla, Hall Catherine N
Sussex Neuroscience, School of Psychology, University of Sussex, Falmer, United Kingdom.
Brighton and Sussex Medical School, Brighton, United Kingdom.
Front Aging Neurosci. 2022 Feb 14;13:779823. doi: 10.3389/fnagi.2021.779823. eCollection 2021.
In understanding the role of the neurovascular unit as both a biomarker and target for disease interventions, it is vital to appreciate how the function of different components of this unit change along the vascular tree. The cells of the neurovascular unit together perform an array of vital functions, protecting the brain from circulating toxins and infection, while providing nutrients and clearing away waste products. To do so, the brain's microvasculature dilates to direct energy substrates to active neurons, regulates access to circulating immune cells, and promotes angiogenesis in response to decreased blood supply, as well as pulsating to help clear waste products and maintain the oxygen supply. Different parts of the cerebrovascular tree contribute differently to various aspects of these functions, and previously, it has been assumed that there are discrete types of vessel along the vascular network that mediate different functions. Another option, however, is that the multiple transitions in function that occur across the vascular network do so at many locations, such that vascular function changes gradually, rather than in sharp steps between clearly distinct vessel types. Here, by reference to new data as well as by reviewing historical and recent literature, we argue that this latter scenario is likely the case and that vascular function gradually changes across the network without clear transition points between arteriole, precapillary arteriole and capillary. This is because classically localized functions are in fact performed by wide swathes of the vasculature, and different functional markers start and stop being expressed at different points along the vascular tree. Furthermore, vascular branch points show alterations in their mural cell morphology that suggest functional specializations irrespective of their position within the network. Together this work emphasizes the need for studies to consider where transitions of different functions occur, and the importance of defining these locations, in order to better understand the vascular network and how to target it to treat disease.
在理解神经血管单元作为疾病干预的生物标志物和靶点的作用时，至关重要的是要认识到该单元不同组成部分的功能如何沿血管树发生变化。神经血管单元的细胞共同执行一系列重要功能，保护大脑免受循环毒素和感染，同时提供营养并清除废物。为此，大脑的微血管会扩张，将能量底物导向活跃的神经元，调节循环免疫细胞的进入，并在血液供应减少时促进血管生成，以及通过搏动来帮助清除废物并维持氧气供应。脑血管树的不同部分对这些功能的各个方面贡献不同，以前人们认为沿着血管网络存在不同类型的血管，它们介导不同的功能。然而，另一种可能性是，在整个血管网络中发生的功能的多次转变在许多位置都会发生，以至于血管功能是逐渐变化的，而不是在明显不同的血管类型之间有明显的阶梯式变化。在这里，通过参考新数据以及回顾历史和近期文献，我们认为后一种情况很可能是事实，即血管功能在整个网络中逐渐变化，在小动脉、毛细血管前小动脉和毛细血管之间没有明显的过渡点。这是因为传统上局部化的功能实际上是由广泛的血管区域执行的，并且不同的功能标志物在血管树的不同点开始和停止表达。此外，血管分支点的壁细胞形态会发生改变，这表明无论它们在网络中的位置如何，都具有功能特化。这项工作共同强调了研究需要考虑不同功能的转变发生在哪里，以及定义这些位置的重要性，以便更好地理解血管网络以及如何针对它来治疗疾病。
