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脉管系统，该过程由现有血管或血管丛中内皮细胞的增殖组成，并导致新血管形成。脑血管化的概念通常将CNS血管生成描述为一种被动过程，主要是由氧气需求驱动，并满足不断增长的神经元种群的代谢需求。他们将发展中的内皮网络视为同质人群。我们的工作对这些观念提出了挑战，并表明尾脑血管属于两类：基于解剖位置，独立的生长模式和发育调节，室内和脑室周围。神经管充当构成神经的血管，指导围绕它的皮拉血管的形成。 PIAL容器不显示发育梯度，并且在胚胎第9天（E9）出现了整个端脑的限制。另一方面，脑室周围的血管是位于基底神经节原基中的基底血管的分支，可能是由E9源自颈椎区域的咽弓动脉引起的。脑室脑血管网络以E11受到同型转录因子调节的E11的有序晶格模式传播到背脑脑。该应用将检验中心假设，即周围的内皮细胞为在胚胎端脑中建立后来形成的神经元梯度提供了关键的线索。它旨在强调周围内皮细胞发育的自主性及其独立于神经元发育的调节。它探讨了一个新的概念，即周围的内皮细胞具有自己的议程，在能够雕刻神经元网络方面具有显着的多功能性。它试图利用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。结果将对概念和调节血管生成的机制具有深远的影响，为端脑组织生成原理提供新的观点，并将导致发现对许多神经系统疾病的治疗前所未有的发现。 公共卫生相关性：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，这将使我们能够开发有效的新疗法，以在许多不同的情况下促进修复脑损伤。