Novel Autonomous Roles of CNS Angiogenesis

摘要 中枢神经系统(CNS)通过血管生成获得血管生成，这一过程对其 开发和修复。我们的工作改变了脑血管形成的概念，这意味着血液 血管从软脑膜血管丛被动地发芽进入脑实质，以满足 不断增长的神经元群体或将中枢神经系统内皮细胞视为同质群体。基于 起源，解剖位置，独立生长模式和发育调节，前脑血管 神经网络分为两类：硬脑膜网络和脑室周围网络。在脑室周围发育的血管网络 神经元发育的发展和独立的战略地位，以提供支持和关键 指导发育中的端脑的神经发生和GABA能神经元间迁移的指导线索。 这些发现为移植的初级神经元前体细胞提供了新的解决方案，这些细胞前体无法迁移和 在缺乏适当的指导机制的情况下，整合到需要新神经元的区域。此应用程序 将以不同的方式探索这一神经血管相互作用的新范例。它将识别小说 神经精神疾病起源和病因学基础上的血管生成机制。它的目的是强调 内皮GABA信号对大脑发育不可或缺的新概念塑造了出生后 以及成年人的行为。它试图挽救胚胎发育过程中异常的血管GABA信号，如 一种治疗方法，以获得长期的心理健康结果。它将检查脑室周围样细胞是否 人内皮细胞促进人GABA能神经元迁移促进新细胞发育 GABA相关疾病的基础疗法。结果将对观念和观念产生深远影响 血管生成的调控机制，为端脑组织发生的原理和机制提供了新的视角 将导致对再生医学和许多疾病的治疗产生前所未有的影响的发现 神经和精神疾病。

Abstract The central nervous system (CNS) acquires its vasculature by angiogenesis, a process that is critical for its development and repair. Our work has changed notions of cerebral vascularization which implied that blood vessels sprout passively into the brain parenchyma from pial vascular plexuses to meet metabolic needs of growing neuronal populations or treated endothelial cells of the CNS as a homogenous population. Based on origins, anatomical location, independent growth patterns and developmental regulation, forebrain vascular networks fall into two categories: pial and periventricular. The periventricular vascular network that develops in advance of and independent of neuronal development is strategically positioned to provide support and critical guidance cues to instruct neurogenesis and GABAergic interneuron migration in the developing telencephalon. These findings offer new solutions for transplanted primary neuronal precursors that are unable to migrate and integrate into regions requiring new neurons in the absence of proper guidance mechanisms. This application will explore this novel paradigm of neurovascular interactions in diverse ways. It will identify novel angiogenesis mechanisms underlying the origin and etiology of neuropsychiatric diseases. It aims to highlight the novel concept that endothelial GABA signaling is indispensable for brain development shaping postnatal and adult behavior. It attempts to rescue abnormal vascular GABA signaling during embryonic development as a therapeutic approach for long-lasting mental health outcomes. It will examine whether periventricular–like human endothelial cells promote human GABAergic neuronal migration to facilitate development of novel cell based therapies for GABA-related diseases. 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 implications for regenerative medicine and treatment of many neurological and psychiatric diseases.