Schwann cell regulation of chronic nerve injury

雪旺细胞对慢性神经损伤的调节

• 批准号: 6935928
• 负责人: Ranjan Gupta
• 金额: $ 30.66万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-08-15 至 2009-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6935928
• 关键词: Schwann cells; apoptosis; axon; carpal tunnel syndrome; cell population study; cell proliferation; cellular pathology; compression; electron microscopy; electrophysiology; laboratory rat; macrophage; male; mixed tissue /cell culture; molecular pathology; myelin; nerve injury; neuronal guidance; neuropathology; neurophysiology; pathologic process; repetitive motion injury

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.

描述（由申请人提供）：本申请旨在研究慢性神经压迫（CNC）损伤中的细胞和分子变化，例如腕管综合征、肘管综合征和脊神经根狭窄。这些局部周围神经病变每年给数百万美国人带来疼痛、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，针对 CNC 患者的有效治疗方法也有限。我们之前的工作表明，与急性神经损伤不同，CNC 损伤的早期阶段不存在轴突病理学；我们最近报道，CNC 损伤会诱导雪旺细胞增殖和凋亡，且可检测到的轴突病理极少。 我们还报告说，CNC 损伤为巨噬细胞募集提供了缓慢、持续的刺激，这与华勒变性巨噬细胞募集的直接信号不同。 这些发现表明，与急性神经损伤相比，CNC 损伤具有根本不同的发病机制。基于我们现有的工作，该应用将评估 CNC 损伤时雪旺细胞增殖的轴突出芽水平，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的影响增殖，并定义机械刺激对雪旺细胞增殖和轴突萌芽的作用。