Nuffield Department of Clinical Neurosciences, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, U.K.
Clin Sci (Lond). 2018 Feb 14;132(3):399-418. doi: 10.1042/CS20160720.
From the earliest stages of development, when cerebral angiogenesis and neurogenesis are entwined, to the end of life, the interplay between vascular and neural systems of the brain is critical in health and disease. Cerebral microvascular endothelial cells constitute the blood-brain barrier and in concert with pericytes or smooth muscle cells, glia and neurons, integrate into a functional neurovascular unit (NVU). This multicellular NVU maintains homoeostasis of the brain's microenvironment by restricting the entry of systemic pathogens and neurotoxins as well as meeting the metabolic demands of neural activity. Recent evidence of cerebral microvascular pathologies in vascular diseases and dementia, including Alzheimer's disease, has challenged the notion that vascular events are merely the consequence of neuronal pathology. This review focuses on molecular mechanisms of neurovascular dysfunction in dementia and outlines currently employed models to decode such mechanisms. Deciphering neurovascular crosstalk is likely to be more important in understanding the molecular mechanisms of disease than previously anticipated and may offer novel therapeutic opportunities for dementia and related conditions.
从大脑血管生成和神经发生交织的早期发育阶段到生命末期，大脑血管系统和神经系统之间的相互作用对健康和疾病都至关重要。脑微血管内皮细胞构成血脑屏障，并与周细胞或平滑肌细胞、神经胶质细胞和神经元一起整合为功能性神经血管单元（NVU）。这个多细胞的 NVU 通过限制全身病原体和神经毒素的进入以及满足神经活动的代谢需求来维持大脑微环境的稳态。血管疾病和痴呆（包括阿尔茨海默病）中大脑微血管病理学的最新证据挑战了血管事件仅仅是神经元病变后果的观点。这篇综述重点关注痴呆症中神经血管功能障碍的分子机制，并概述了目前用于解码这些机制的模型。解析神经血管相互作用可能比以前预期的更重要，有助于理解疾病的分子机制，并为痴呆症和相关疾病提供新的治疗机会。
