The Autonomous Roles of Periventricular Angiogenesis in the CNS

中枢神经系统室周血管生成的自主作用

• 批准号: 8083551
• 负责人: Anju Vasudevan
• 金额: $ 34.56万
• 依托单位: MCLEAN HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-04-01 至 2016-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8083551
• 关键词: Arteries; Basal Ganglia; Blood Vessels; Brain; Brain Injuries; Branchial arch structure; Categories; Cells; Cerebrum; Cervical; Cues; Development; Diamond; Dorsal; Embryo; Endothelial Cells; Gap Junctions; Gene Expression; Genes; Genetic; Growth; Homeobox; Immigration; Impairment; In Vitro; Lead; Location; Metabolic; Microarray Analysis; Migration Assay; Modeling; Molds; Nervous System Physiology; Neural tube; Neuraxis; Neuroepithelial Cells; Neurons; Oxygen; Pattern; Play; Population; Positioning Attribute; Primordium; Process; Public Health; Radial; Recovery; Regulation; Research; Role; Route; Schedule; Shadowing (Histology); Source; Staging; Stream; Telencephalon; Testing; Therapeutic; Transplantation; Vascularization; Work; angiogenesis; base; falls; gamma-Aminobutyric Acid; histogenesis; in vivo; insight; loss of function; meetings; migration; nervous system disorder; neurogenesis; neuron development; novel; perineural; programs; repaired; striosome; system architecture; transcription factor

DESCRIPTION (provided by applicant): The central nervous system (CNS) acquires its vasculature by angiogenesis, a process consisting of proliferation of endothelial cells in existing blood vessels or vascular plexuses, and leading to the formation of new blood vessels. Notions of cerebral vascularization often depict CNS angiogenesis as a passive process driven primarily by demands of oxygen and to meet the metabolic needs of growing neuronal populations. They treat the developing endothelial network as a homogenous population. Our work has challenged these notions and shown that telencephalic blood vessels fall into two categories: pial and periventricular, based on anatomical location, independent growth patterns and developmental regulation. The neural tube acting as a vessel patterning nexus, directs the formation of the pial vessels that encompass it. The pial vessels do not display developmental gradients and are present circumscribing the entire telencephalon by embryonic day 9 (E9). The periventricular vessels on the other hand are branches of a basal vessel located in the basal ganglia primordium that likely arises from the pharyngeal arch arteries in the cervical region by E9. The periventricular vessel network propagates in an orderly lattice pattern into the dorsal telencephalon by E11 regulated by homeobox transcription factors. This application will test the central hypothesis that periventricular endothelial cells provide critical cues for the establishment of later forming neuronal gradients in the embryonic telencephalon. It aims at highlighting the autonomy of periventricular endothelial cell development and how it is regulated independently of neuronal development. It explores the novel concept that periventricular endothelial cells have an agenda of their own with remarkable versatility in being able to sculpt neuronal networks. It attempts to tap into the tremendous potential of periventricular endothelial cells as a therapeutic source for recovery of neurological function in many diverse scenarios. Results will have far-reaching effects on concepts and mechanisms of regulation of angiogenesis, offer new perspectives on telencephalic histogenesis principles and will lead to discoveries with unprecedented implication for treatment of many neurological disorders. PUBLIC HEALTH RELEVANCE: This research is relevant to public health because it will offer novel insights into CNS angiogenesis that will permit us to develop effective and new therapies to promote repair of brain damage in many diverse scenarios.

描述（由申请人提供）：中枢神经系统（CNS）通过血管生成获得其血管系统，血管生成是一个由现有血管或血管丛中的内皮细胞增殖组成的过程，并导致新血管的形成。脑血管化的概念通常将CNS血管生成描述为主要由氧需求驱动的被动过程，以满足生长的神经元群体的代谢需求。他们将发育中的内皮网络视为同质群体。我们的工作挑战了这些概念，并表明端脑血管分为两类：软脑膜和脑室周围，基于解剖位置，独立的生长模式和发育调节。神经管作为一个血管图案的联系，指导软脑膜血管的形成，包括它。软脑膜血管不显示发育梯度，并在胚胎第9天（E9）的整个端脑外。另一方面，室周血管是位于基底神经节原基中的基底血管的分支，其可能在E9时从颈部区域的咽弓动脉产生。室周血管网络在同源框转录因子的调控下通过E11以有序的网格模式传播到端脑背侧。这个应用程序将测试中央假设，即室周内皮细胞提供了关键线索，后来形成神经元梯度在胚胎端脑的建立。它的目的是强调室周内皮细胞发育的自主性，以及它是如何独立于神经元发育进行调节的。它探讨了新的概念，即室周内皮细胞有自己的议程，具有显着的多功能性，能够塑造神经元网络。它试图挖掘室周内皮细胞作为在许多不同情况下恢复神经功能的治疗来源的巨大潜力。这些结果将对血管生成调控的概念和机制产生深远的影响，为端脑组织发生原理提供新的视角，并将为许多神经系统疾病的治疗带来前所未有的意义。 公共卫生关系：这项研究与公共卫生有关，因为它将为CNS血管生成提供新的见解，使我们能够开发有效的新疗法，以促进许多不同情况下的脑损伤修复。