Schwann cell regulation of chronic nerve injury

描述（由申请人提供）：本申请旨在研究慢性神经压迫（CNC）损伤（如腕管综合征、肘管综合征和脊神经根狭窄）中的细胞和分子变化。这些局部的周围神经病变每年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是有限的，CNC患者的有效治疗方法也是如此。我们以前的工作表明，轴突病理是不存在的CNC损伤的早期阶段，与急性神经损伤，我们最近报道，CNC损伤诱导雪旺细胞增殖和凋亡，最小的可检测的轴突病理。 我们还报道了CNC损伤为巨噬细胞募集提供了缓慢、持续的刺激，这与Wallerian变性的巨噬细胞募集的直接信号不同。 这些结果表明，CNC损伤有一个根本不同的发病机制相比，急性神经损伤。在我们现有工作的基础上，该应用将评估CNC损伤的雪旺细胞增殖的轴突发芽水平，评估CNC损伤后早期雪旺细胞的变化如何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发芽的作用。

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.