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

• 批准号: 8872372
• 负责人: DWIGHT E BERGLES
• 金额: $ 24.3万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 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/8872372
• 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; 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; 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 therapeutics; oligodendrocyte precursor; precursor cell; progenitor; public health relevance; remyelination; repaired; research study; response; spinal cord repair; therapeutic target; tissue repair; tool; two-photon; white matter

 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）：美国大约有 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 引发神经胶质细胞行为的深刻变化，从而限制继发性损伤并影响再生。然而，不同神经胶质细胞类型在 SCI 恢复过程中的不同作用尚不清楚。 NG2+ 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 SCI 后迅速动员；他们增加增殖并迁移到该地点 的伤害。 NG2+ 细胞招募的后果尚不清楚。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额外的作用。在这项探索性研究资助 (R21) 中，我们建议在临床相关的挫伤诱发 SCI 模型中使用体内遗传谱系追踪、体内双光子成像和体内选择性细胞消融来检查这些高度动态细胞的命运，并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纵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)）的靶向操纵的新治疗策略。