EXPERIMENTAL CHRONIC ENTRAPMENT NEUROPATHY

实验性慢性卡压性神经病

• 批准号: 3397902
• 负责人: PHILLIP A LOW
• 金额: $ 6.75万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 1983
• 资助国家: 美国
• 起止时间: 1983-04-01 至 1986-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3397902
• 关键词: axon; biophysics; body fluids; disease /disorder model; ischemia; myelinopathy; neurotoxins; peripheral nervous system; peripheral nervous system disorders; radiotracer; stress

The entrapment neuropathies are the most common type of neuropathies affecting man and cause major personal and economic impact. We have developed a model of chronic entrapment in rats and rabbits which regularly cause focal demyelination. Methodology has been developed in this laboratory to directly measure endoneurial fluid pressure and blood flow within the entrapped region. By relating endoneurial fluid pressure and blood flow values to the focal pathologic changes, it will be possible to directly test the hypothesis that entrapment induced demyelination is caused by local and focal collapse of capillaries or other ischmic mechanisms. By systematically relating pressure: volume changes to axon volume and shape changes at multiple levels using detailed morphometry it will be possible to define the type an quantity of biophysical stresses that cause demyelination. This approach has previously not been possible. Peripheral nerve perineurium is distorted at the cuff edge and should perineurial permeability or compliance become abnormal at these regions there may occur an influx of potentially neurotoxic compounds into the endoneurium of nerve. We plan to directly measure perineurial compliance of the entrapped region using a sensitive in vitro active servo-null system and to test if permeability is increased using two isotopes (C14 sucrose, I125 albumin) in entrapped and normal fibers and the same fibers when stressed to 5 mm mercury. The endoneurial fluid pressure and morphometric studies will be performed in year 1, compliance and permeability studies in year 2 and intrafascicular blood flow studies in year 3.

嵌顿性神经病是最常见的神经病类型。 影响人类，并造成重大的个人和经济影响。我们有 在大鼠和兔身上建立了一种慢性困住模型，该模型定期地 导致局灶性脱髓鞘。方法论已经在这方面得到了发展 直接测量神经内液压力和血流量的实验室 在被困区域内。通过将神经内液压力和 血流值对局灶性病变，才有可能 直接测试以下假设：诱导性脱髓鞘是 由局部和局灶性毛细血管或其他缺血引起 机制。通过系统地关联压力：轴突的体积变化 使用详细的形态计量学在多个层次上改变体积和形状 将有可能定义生物物理压力的类型和数量 会导致脱髓鞘。这种方法以前是不可能的。 周围神经束膜在袖带边缘变形，应该 神经膜通透性或顺应性在这些区域变得异常 可能会有潜在的神经毒性化合物涌入 神经内膜。我们计划直接测量会顺应性 使用灵敏的体外主动伺服零位系统检测被困区域 并测试使用两种同位素(C14蔗糖， I125白蛋白)在包裹的和正常的纤维以及相同的纤维中 应激至5毫米汞。神经内液压力与形态计量学 研究将在第一年进行，遵从性和渗透性研究 在第二年和第三年进行束内血流研究。