Role of NG2+ glial cells in recovery from spinal cord injury

NG2 胶质细胞在脊髓损伤恢复中的作用

基本信息

批准号：
9011389
负责人：
DWIGHT E BERGLES
金额：
$ 20.25万
依托单位：
JOHNS HOPKINS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-02-15 至 2017-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9011389
关键词：
ARHGEF5 gene Ablation Adult Affect Axon Behavior Brain CSPG4 gene Cell Proliferation Cells Cicatrix Contusions Data Development Environment Evolution Excision Functional disorder Genetic Health Healthcare Systems Image Injury Knowledge Lasers Life Modeling Mus Myelin Natural regeneration Neuraxis Neuroglia Oligodendroglia Paralysed Play Population Process Proteoglycan Recovery Recovery of Function Research Project Grants Rodent Model Role Site Source Spinal Spinal Cord Spinal cord injury Stem cells Technology Time Transgenic Model Transplantation Trauma Traumatic injury United States base behavioral study cell behavior cell motility cell type cellular engineering central nervous system injury clinically relevant cost design gray matter in vivo in vivo imaging injury and repair insight interest migration mouse model neuroprotection novel novel therapeutic intervention oligodendrocyte precursor precursor cell progenitor remyelination repaired research study response spinal cord repair therapeutic target tissue repair tool two-photon white matter

项目摘要

DESCRIPTION (provided by applicant): Approximately 5,596,000 people in the United States live with some form of paralysis; among these, 1,275,000 are paralyzed as the result of a spinal cord injury (SCI). The lack of treatment results in a constantly growing population. Each year, SCI cost to the health care system is roughly 40.5 billion. SCI triggers profound changes in the behavior of glial cells, which limit secondary injury and influence regeneration. However, the distinct roles of different glial cell types in the recovery from SCI are not well understood. NG2+ glial cells, a class of glial progenitors that generate oligodendrocytes in the developing and adul CNS, are rapidly mobilized following SCI; they increase their proliferation and migrate to the site of injury. The consequences of this recruitment of NG2+ cells are unknown. Although the behavior of these cells has been viewed primarily in the context of oligodendrocyte regeneration, recent studies suggest that they may play additional roles in the pathophysiology of SCI. In this exploratory research grant (R21) we propose to examine the fate of these highly dynamic cells and evaluate their contribution to functional recovery using in vivo genetic lineage tracing, in vivo two photon imaging, and in vivo selective cell ablation in a clinically relevant model of contusion-induced SCI. The knowledge gained from these studies may reveal new therapeutic strategies based on manipulation of this endogenous pool of progenitors as well as targeted manipulation of NG2+ cells (also termed oligodendrocyte precursor cells (OPCs) engineered for transplantation therapy.

描述（由申请人提供）：美国约有 5,596,000 人患有某种形式的瘫痪；其中 1,275,000 人因脊髓损伤（SCI）而瘫痪。缺乏治疗导致人口不断增长。每年，SCI 给医疗保健系统造成的损失约为 405 亿美元。 SCI 会引发神经胶质细胞行为的深刻变化，从而导致神经胶质细胞的行为发生深刻变化。然而，不同神经胶质细胞类型在 SCI 恢复中的不同作用尚不清楚。神经胶质细胞是一类神经胶质祖细胞，在发育中和成年的中枢神经系统中产生少突胶质细胞，在脊髓损伤后迅速动员，它们增加增殖并迁移到该部位；尽管这些细胞的行为主要是在少突胶质细胞再生的背景下观察的，但最近的研究表明它们可能在 SCI 的病理生理学中发挥其他作用。资助（R21），我们建议检查这些高度动态细胞的命运，并使用体内遗传谱系追踪、体内双光子成像和临床相关的体内选择性细胞消融来评估它们对功能恢复的贡献。从这些研究中获得的知识可能会揭示基于内源性祖细胞库的操作以及针对移植治疗而设计的 NG2+ 细胞（也称为少突胶质细胞前体细胞 (OPC)）的靶向操作的新治疗策略。