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

 描述(申请人提供)：美国约有5596,000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，医疗保健系统的SCI成本约为405亿美元。脊髓损伤后，神经胶质细胞的行为发生了深刻的变化，限制了继发性损伤，影响了再生。然而，不同类型的胶质细胞在脊髓损伤后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前体细胞，在发育和成熟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，促进其增殖并迁移到损伤部位。 受伤的原因。NG2细胞的这种招募的后果尚不清楚。虽然这些细胞的行为主要是在少突胶质细胞再生的背景下被观察到的，但最近的研究表明，它们可能在脊髓损伤的病理生理学中起着额外的作用。在这项探索性研究拨款(R21)中，我们建议在临床相关的挫伤诱导脊髓损伤模型中，通过体内遗传谱系追踪、体内双光子成像和体内选择性细胞消融来检查这些高活力细胞的命运，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对内源性祖细胞池的操纵以及对NG2细胞(也称为用于移植治疗的少突胶质前体细胞(OPC)的靶向操纵)的新的治疗策略。

 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.