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: 8638821
• 负责人: Anju Vasudevan
• 金额: $ 34.22万
• 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/8638821
• 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; public health relevance; 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.

描述（由申请人提供）：中枢神经系统（CNS）通过血管生成获得其脉管系统，该过程包括现有血管或血管丛中内皮细胞的增殖，并导致新血管的形成。脑血管化的概念通常将中枢神经系统血管生成描述为主要由氧气需求驱动并满足不断增长的神经元群的代谢需求的被动过程。他们将正在发育的内皮网络视为同质群体。我们的工作挑战了这些概念，并表明端脑血管根据解剖位置、独立生长模式和发育调节分为两类：软脑膜血管和脑室周围血管。神经管作为血管模式连接，指导包围它的软脑膜血管的形成。软脑膜血管不显示发育梯度，并且在胚胎第 9 天 (E9) 时就存在围绕整个端脑。另一方面，脑室周围血管是位于基底神经节原基中的基底血管的分支，其可能由 E9 源自颈部区域的咽弓动脉。脑室周围血管网络通过受同源框转录因子调节的 E11 以有序的格子模式传播到背侧端脑。该应用将测试中心假设，即室周内皮细胞为胚胎端脑中后来形成的神经元梯度的建立提供关键线索。它的目的是强调心室周围内皮细胞发育的自主性以及它如何独立于神经元发育进行调节。它探索了一个新概念，即心室周围内皮细胞有自己的议程，在塑造神经元网络方面具有显着的多功能性。它试图挖掘脑室周围内皮细胞的巨大潜力，作为在许多不同情况下恢复神经功能的治疗来源。结果将对血管生成调节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，并将导致对许多神经系统疾病的治疗具有前所未有的意义的发现。