Novel Autonomous Roles of CNS Angiogenesis

中枢神经系统血管生成的新自主作用

基本信息

批准号：
10242957
负责人：
Anju Vasudevan
金额：
$ 33.99万
依托单位：
HUNTINGTON MEDICAL RESEARCH INSTITUTES
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-09-30 至 2023-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10242957
关键词：
Adopted Adult Affect Anatomy Angiogenesis Pathway Anxiety Behavior Behavioral Behavioral Mechanisms Behavioral Symptoms Blood Vessels Blood flow Brain Categories Cell Therapy Cell surface Cells Cerebral cortex Cerebrum Characteristics Complex Cues Defect Development Disease Embryo Embryonic Development Endothelial Cells Endothelium Epilepsy Equilibrium Etiology GAD65 enzyme GAD67 enzyme Gene Expression Gene Expression Profile Genes Glutamates Growth Human Impairment In Vitro Interneurons Knowledge Location Mental Depression Mental Health Mental disorders Metabolic Midbrain structure Molecular Mus Natural regeneration Neuraxis Neurons Outcome Pathogenesis Pathway interactions Pattern Population Positioning Attribute Process Prosencephalon Proteins Public Health Radial Regenerative Medicine Regulation Research Role Schizophrenia Shapes Signal Transduction Synaptosomes Telencephalon Testing Therapeutic Transplantation Vascularization Ventricular Work angiogenesis autism spectrum disorder base brain endothelial cell brain parenchyma cell motility conditional knockout design developmental disease effective therapy falls gamma-Aminobutyric Acid genetic approach histogenesis in vivo insight migration mouse model nerve stem cell nervous system disorder neurogenesis neuron development neuropsychiatric disorder neuropsychiatry neurovascular novel novel strategies postnatal prenatal prevent psychiatric symptom receptor regenerative treatment repaired vascular abnormality vesicular GABA transporter

项目摘要

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.

抽象的中枢神经系统（CNS）通过血管生成获得其脉管系统，这一过程对它的脉管发生至关重要开发和维修。我们的工作改变了脑血管的笔记，这暗示着血液血管从伴侣血管丛中被动地发芽到大脑实质中，以满足代谢需求将中枢神经系统的神经元种群或治疗的内皮细胞作为同质种群。基于起源，解剖位置，独立的生长模式和发育调节，前脑血管网络分为两类：pial和周期性。在在战略上可以提供支持和关键指导发育中脑脑中神经发生和GABA能中神经元迁移的指导提示。这些发现为无法迁移的移植主要神经元前体提供了新的解决方案在没有适当的指导机制的情况下整合到需要新神经元的区域。此应用程序将以潜水员方式探索这种神经血管相互作用的新型范式。它将识别出小说神经精神疾病起源和病因的基础的血管生成机制。它旨在突出显示内皮GABA信号传导对于大脑发育塑造产后必不可少的新颖概念是必不可少的和成人行为。它试图在胚胎发育过程中营救异常的血管GABA信号传导一种治疗方法，用于持久的心理健康结果。它将检查周期性人内皮细胞促进人GABA能神经元迁移，以促进新细胞的发展基于与GABA相关疾病的疗法。结果将对概念和血管生成调节的机制，提供有关尾脑组织发生原理和的新观点将导致发现对再生医学的前所未有的发现，并治疗许多神经和精神病。