Novel Autonomous Roles of CNS Angiogenesis

摘要 中枢神经系统 (CNS) 通过血管生成获得脉管系统，这一过程对于其正常运转至关重要 开发和修复。我们的工作改变了脑血管化的概念，这意味着血液 血管从软脑膜血管丛被动地长入脑实质，以满足新陈代谢的需要 生长的神经元群体或将中枢神经系统的内皮细胞作为同质群体进行处理。基于 起源、解剖位置、独立生长模式和发育调节、前脑血管 网络分为两类：软脑膜网络和脑室周围网络。脑室周围血管网络发育于 神经元发育的进步和独立于神经元发育的战略定位是提供支持和关键 指导发育中端脑神经发生和 GABA 能中间神经元迁移的引导线索。 这些发现为无法迁移和迁移的移植原代神经元前体提供了新的解决方案 在缺乏适当引导机制的情况下整合到需要新神经元的区域。这个应用程序 将以不同的方式探索这种神经血管相互作用的新范式。它将识别小说 神经精神疾病的起源和病因学的血管生成机制。其目的在于突出 内皮 GABA 信号对于出生后大脑发育不可或缺的新概念 和成人行为。它试图挽救胚胎发育过程中异常的血管 GABA 信号传导 一种可实现持久心理健康结果的治疗方法。它将检查是否有脑室周围样 人内皮细胞促进人 GABA 能神经元迁移，以促进新细胞的发育 GABA 相关疾病的基础疗法。结果将对概念和概念产生深远影响 血管生成的调节机制，为端脑组织发生原理提供新的视角 将对再生医学和许多疾病的治疗产生前所未有的影响 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.