Zarekiani Parand, Nogueira Pinto Henrique, Hol Elly M, Bugiani Marianna, de Vries Helga E
Department of Pathology, Amsterdam Neuroscience, Amsterdam UMC, Vrije Universiteit Amsterdam, de Boelelaan 1117, Amsterdam, The Netherlands.
Amsterdam Leukodystrophy Center, Amsterdam UMC, Amsterdam, The Netherlands.
Fluids Barriers CNS. 2022 Feb 28;19(1):18. doi: 10.1186/s12987-022-00316-0.
The neurovascular unit (NVU) is a highly organized multicellular system localized in the brain, formed by neuronal, glial (astrocytes, oligodendrocytes, and microglia) and vascular (endothelial cells and pericytes) cells. The blood-brain barrier, a complex and dynamic endothelial cell barrier in the brain microvasculature that separates the blood from the brain parenchyma, is a component of the NVU. In a variety of neurological disorders, including Alzheimer's disease, multiple sclerosis, and stroke, dysfunctions of the NVU occurs. There is, however, a lack of knowledge regarding the NVU function in leukodystrophies, which are rare monogenic disorders that primarily affect the white matter. Since leukodystrophies are rare diseases, human brain tissue availability is scarce and representative animal models that significantly recapitulate the disease are difficult to develop. The introduction of human induced pluripotent stem cells (hiPSC) now makes it possible to surpass these limitations while maintaining the ability to work in a biologically relevant human context and safeguarding the genetic background of the patient. This review aims to provide further insights into the NVU functioning in leukodystrophies, with a special focus on iPSC-derived models that can be used to dissect neurovascular pathophysiology in these diseases.
神经血管单元（NVU）是位于大脑中的一个高度组织化的多细胞系统，由神经元、神经胶质细胞（星形胶质细胞、少突胶质细胞和小胶质细胞）和血管细胞（内皮细胞和周细胞）组成。血脑屏障是脑微血管中一个复杂且动态的内皮细胞屏障，它将血液与脑实质分隔开，是神经血管单元的一个组成部分。在包括阿尔茨海默病、多发性硬化症和中风在内的多种神经系统疾病中，神经血管单元都会出现功能障碍。然而，对于脑白质营养不良（一种主要影响白质的罕见单基因疾病）中神经血管单元的功能，我们还缺乏了解。由于脑白质营养不良是罕见疾病，人类脑组织难以获取，而且很难开发出能显著重现该疾病的代表性动物模型。人类诱导多能干细胞（hiPSC）的引入，使得在保持在生物学相关的人类环境中开展研究的能力并保留患者遗传背景的同时，克服这些限制成为可能。本综述旨在进一步深入了解脑白质营养不良中神经血管单元的功能，特别关注可用于剖析这些疾病中神经血管病理生理学的iPSC衍生模型。
