Schwann cell regulation of chronic nerve injury

描述(申请人提供)：本申请建议研究慢性神经压迫(CNC)损伤的细胞和分子变化，如腕管综合征、肘管综合征和脊神经根狭窄。这些局限性的外周神经病每年会在数百万美国人中产生疼痛、感觉改变和运动萎缩。然而，关于导致损伤的细胞和分子事件级联的知识有限，对于数控患者的有效治疗的数量也是有限的。我们以前的工作表明，与急性神经损伤不同，计算机数控系统损伤的早期阶段没有轴突病理；我们最近报道，计算机控制系统损伤同时诱导雪旺细胞增殖和凋亡，仅有极少量的轴突病理可检测到。我们还报告说，电脑控制损伤为巨噬细胞募集提供了一种缓慢而持续的刺激，这不同于沃勒变性对巨噬细胞募集的直接信号。这些发现表明，与急性神经损伤相比，数控损伤具有根本不同的发病机制。在我们现有工作的基础上，这项应用将评估CNC损伤后雪旺细胞增殖的轴突萌发水平，评估CNC损伤后早期雪旺细胞如何变化直接改变神经生理学，确定巨噬细胞募集的程度及其对雪旺细胞增殖的影响，并确定机械刺激对雪旺细胞增殖和轴突萌发的作用。

DESCRIPTION (provided by applicant): This application proposes to investigate cellular and molecular changes in chronic nerve compression (CNC) injuries, such as carpal tunnel syndrome, cubital tunnel syndrome, and spinal nerve root stenosis. These localized, peripheral neuropathies produce pain, altered sensation, and motor atrophy in millions of Americans each year. However, knowledge about the cascade of cellular and molecular events leading to injury is limited, as are the number of effective treatments for CNC patients. Our previous work suggests that axonal pathology is absent in the early phases of CNC injury, unlike with acute neural injuries; we recently reported that CNC injury induces both Schwann cell proliferation and apoptosis, with minimal detectable axonal pathology. We also reported that CNC injury provides a slow, sustained stimulus for macrophage recruitment, which differs from Wallerian degeneration's immediate signal for macrophage recruitment. These findings suggest that CNC injuries have a fundamentally distinct pathogenesis compared with acute nerve injuries. Building on our existing work, this application will assess the level of axonal sprouting with the Schwann cell proliferation of CNC injury, evaluate how the early Schwann cell changes after CNC injury directly alter neurophysiology, determine the extent of macrophage recruitment and its effect on Schwann cell proliferation, and define the role of mechanical stimulation on Schwann cell proliferation and axonal sprouting.