Eph Receptors Regulate Vascular Growth Following Traumatic Brain Injury

Eph 受体调节脑外伤后的血管生长

基本信息

批准号：
8786273
负责人：
Poincyane Assis-Nascimento
金额：
$ 4.27万
依托单位：
UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-07-01 至 2015-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8786273
关键词：
3-Dimensional Acute Address Adult Affect Age Angiogenic Proteins Angiopoietin-2 Behavior Behavioral Binding Proteins Blood Vessels Brain Cell Communication Cell Count Cell Death Cell Proliferation Cell Survival Cells Cerebral cortex Cessation of life Co-Immunoprecipitations Cognitive Computer software Country Development Dominant-Negative Mutation Endothelial Cells Eph Family Receptors EphB3 Receptor Ephrins Event Exposure to Flow Cytometry Functional disorder Growth Immunohistochemistry In Vitro Individual Injury Investments Knock-out Knockout Mice Lead Left Ligands Light Measures Membrane Methods Microscopy Modeling Motor Mus Nervous system structure Neurons Nutrient Oligodendroglia Outcome Measure Oxygen Pathology Patients Pericytes Play Public Health Recovery Recovery of Function Reporter Retina Role Series Signal Transduction Social Interaction Survivors Techniques Testing Three-Dimensional Imaging Three-dimensional analysis Time Tissues Transgenes Transgenic Mice Transgenic Organisms Traumatic Brain Injury United States Vascular Endothelial Growth Factor Receptor-1 Vascular Endothelial Growth Factors Vascular remodeling Venous angiogenesis cognitive function controlled cortical impact cost disability gain of function improved in vivo injured loss of function medical complication neovascularization novel strategies overexpression protein protein interaction public health relevance receptor research study response spatiotemporal tool

项目摘要

DESCRIPTION (provided by applicant): One of the earliest and most profound deficits that results from traumatic brain injury (TBI) comes from damage to the vascular networks that ultimately underlies much of the progressive pathophysiology associated with TBI. Unfortunately, little is known of the cellular signs and responses that regulate vessel integrity and/or remodeling in the injured brain. The objective of this study is to examine the role of ephrinB3 and EphB3 in vascular injury and regrowth following TBI. B-class ephrin and Eph receptors are both membrane bound proteins that initiate bidirectional signals during cell-cell interactions. In the developing nervous system, ephrinB2-EphB4 interactions have been shown to play essential roles in forming arterial-venous specifications to determine vessel identity; however, the role of other ephrins/Ephs is less clear. Our preliminary findings suggest that ephrinB3 and EphB3 may also play critical roles in angiogenesis in the cerebral cortex. We hypothesize that a subpopulation of endothelial cells (ECs) and pericytes express EphB3 and ephrinB3, respectively, and signal to restrict EC proliferation and vascular regrowth in the injured cortex. To test this hypothesis we will examine the spatiotemporal changes in ephrinB3/EphB3, effects of ephrinB3/EphB3 on vascular stability and regrowth using loss- and gain-of-function approaches, and influences of vascular growth on the survival of other residential cells in the TBI penumbra. We will also take advantage of flow cytometry, EC-specific inducible mice, light-sheet microscopy, newly developed 3-D quantification, as well as behavior analysis. These studies will provide a novel approach to examine the influence of vascular growth on injury progression in the brain.

描述（由申请人提供）：创伤性脑损伤（TBI）引起的最早，最深刻的缺陷之一是对血管网络的损害，最终是与TBI相关的许多进行性病理生理学的基础。不幸的是，对调节受伤大脑中血管完整性和/或重塑的细胞体征和反应知之甚少。这项研究的目的是检查Ephrinb3和Ephb3在TBI后血管损伤和再生中的作用。 B级ephrin和EPH受体都是膜结合蛋白，在细胞 - 细胞相互作用过程中启动双向信号。在发展中的神经系统中，Ephrinb2-EPHB4相互作用已被证明在形成动脉 - 偶然规格中起着至关重要的作用，以确定血管身份。但是，其他晶状体/ephs的作用尚不清楚。我们的初步发现表明，ephrinb3和ephb3也可能在脑皮质中的血管生成中起关键作用。我们假设内皮细胞（EC）和周细胞的亚群分别表达Ephb3和Ephrinb3，并信号限制了受伤的皮质中EC增殖和血管再生。为了检验这一假设，我们将使用Ephrinb3/ephb3的时空变化，Ephrinb3/Ephb3对使用损失和功能性方法的影响以及血管生长对TBI Penumbra中其他住宅细胞存活的影响。我们还将利用流式细胞仪，EC特异性诱导小鼠，灯表显微镜，新开发的3D定量以及行为分析。这些研究将提供一种新的方法来检查血管生长对大脑损伤进展的影响。

项目成果

期刊论文数量（1）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Eph/Ephrin Signaling Controls Progenitor Identities In The Ventral Spinal Cord.

DOI：
10.1186/s13064-017-0087-0
发表时间：
2017-06-08
期刊：
Neural development
影响因子：
3.6
作者：
Laussu J;Audouard C;Kischel A;Assis-Nascimento P;Escalas N;Liebl DJ;Soula C;Davy A
通讯作者：
Davy A