Group of CNS Angiogenesis and Neurovascular Link, Neuroscience Center Zurich, and Division of Neurosurgery, University and University Hospital Zurich, Swiss Federal Institute of Technology (ETH) Zurich, Zurich, Switzerland.
Division of Neurosurgery, University Hospital Zurich, Zurich, Switzerland.
Nat Rev Neurosci. 2023 May;24(5):271-298. doi: 10.1038/s41583-023-00684-y. Epub 2023 Mar 20.
The CNS critically relies on the formation and proper function of its vasculature during development, adult homeostasis and disease. Angiogenesis - the formation of new blood vessels - is highly active during brain development, enters almost complete quiescence in the healthy adult brain and is reactivated in vascular-dependent brain pathologies such as brain vascular malformations and brain tumours. Despite major advances in the understanding of the cellular and molecular mechanisms driving angiogenesis in peripheral tissues, developmental signalling pathways orchestrating angiogenic processes in the healthy and the diseased CNS remain incompletely understood. Molecular signalling pathways of the 'neurovascular link' defining common mechanisms of nerve and vessel wiring have emerged as crucial regulators of peripheral vascular growth, but their relevance for angiogenesis in brain development and disease remains largely unexplored. Here we review the current knowledge of general and CNS-specific mechanisms of angiogenesis during brain development and in brain vascular malformations and brain tumours, including how key molecular signalling pathways are reactivated in vascular-dependent diseases. We also discuss how these topics can be studied in the single-cell multi-omics era.
中枢神经系统(CNS)在发育、成人稳态和疾病过程中严重依赖其血管系统的形成和正常功能。血管生成——新血管的形成——在大脑发育过程中非常活跃,在健康成年大脑中几乎完全静止,并且在血管依赖性脑病变(如脑血管畸形和脑肿瘤)中重新激活。尽管在理解驱动外周组织血管生成的细胞和分子机制方面取得了重大进展,但协调健康和患病中枢神经系统中血管生成过程的发育信号通路仍未完全理解。定义神经和血管布线共同机制的“神经血管连接”的分子信号通路已成为外周血管生长的关键调节剂,但它们对大脑发育和疾病中的血管生成的相关性在很大程度上仍未得到探索。在这里,我们回顾了在大脑发育和脑血管畸形及脑肿瘤过程中血管生成的一般和中枢神经系统特异性机制的最新知识,包括关键分子信号通路如何在血管依赖性疾病中重新激活。我们还讨论了如何在单细胞多组学时代研究这些主题。