NERVE BLOOD FLOW IN NORMAL AND ISCHEMIC PERIPHERAL NERVE

正常和缺血性周围神经的神经血流量

• 批准号: 3404596
• 负责人: PHILLIP A LOW
• 金额: $ 15.93万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-07-01 至 1995-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3404596
• 关键词: autoradiography; axon; biopsy; calcium channel blockers; capillary; catalase; catecholamines; cholesterol; corticosteroids; denervation; diabetic neuropathy; disease /disorder model; eicosanoids; electrophysiology; embolism; free radicals; human tissue; ischemia; laboratory rat; microcirculation; microelectrodes; oxygen; perfusion; peripheral nervous system; polarography; reperfusion; superoxide dismutase; sympathetic nervous system; tritium; vasodilators

Nerve microvasculature is physiologically unique, being a poorly autoregulating, nutritive-capacitance system of large capillaries that is relatively resistant to ischemia. Yet angiopathic neuropathies occur, are relatively common and are difficult to treat. Nerve ischemia may also occur in disorders such as diabetic , edematous and entrapment neuropathies. The broad aim of this continuation proposal is an intensified focus on the physiology of nerve ischemia. The specific aims, rationale, and methods proposed are: First, a 3-dimensional reconstruction of nerve blood flow (NBF) in ischemic models of neuropathy and in response to sympathetic stimulation and denervation. Studies to date on the physiology of nerve ischemia have been unidimensional, focusing on nerve trunk and neglecting the much more metabolically active cell body and at-risk distal axon. By using combined microelectrode-H2-polarography and 14C- iodoantipyrine autoradiography, it should be possible to determine flow simultaneously at the cell body (dorsal root and sympathetic ganglia) and the nerve fiber levels. Second, an evaluation of the molecular mechanisms of nerve ischemic and reperfusion injury on which information is totally lacking. The hypothesis that nerve is damaged during ischemia and reperfusion due to an interplay of oxygen free radicals (OFR) and eicosanoids will be tested. NBF, computerized videoangiology, blood-nerve barrier (BNB; to 14C- sucrose) and nerve electrophysiologic indices will be supplemented by estimations of nerve cholesterol, arachidonic acid, fatty acid profile, malondialdehyde (MDA) and superoxide dismutase (SOD) as indices of OFR damage and the biosynthesis by nerve in situ and in vitro of thromboxane B2 and 6-keto-PFG1 alpha will be used as indices of nerve eiscosanoids and nerve catecholamines will be measured. These studies will be done during ischemia and following reperfusion. Third, an evaluation of mechanisms to ameliorate the effects of ischemia and reperfusion. Calcium channel blockers, vasodilator eiscosanoids, corticosteroids, pentoxifylline and ketanserin may ameliorate microvascular ischemia in other tissues, but their mechanisms and effectiveness in peripheral nerve is unknown. Since the time-course of ischemic fiber damage is very slow, occurring over many hours, nerve comprises a system particularly suited for intervention therapy should it become available. Finally, nerve catecholamines, eicosanoids, MDA and SOD will be measured in sural nerve biopsied for reasons unrelated to this proposal to apply some of these techniques and strategies to humans.

神经微脉管系统在生理上是独一无二的，很差 大毛细血管的自动调节，营养含量系统 那对缺血相对抗药性。 但是血管病 神经病发生，相对常见，很难 对待。 神经缺血也可能发生在诸如 糖尿病，水肿和诱捕神经病。 宽阔 该延续建议的目的是对 神经缺血的生理学。 具体目的，理由和 提出的方法是：首先，3维重建 神经病的缺血模型和中的神经血流（NBF） 对同情刺激和神经支配的反应。 研究 关于神经缺血生理学的日期 一维，专注于神经躯干，忽略了很多 更代谢活性的细胞体和高危远端轴突。 经过 使用微电极-H2造影术和14C- iodoantipyrine放射自显影，应该可以确定 同时在细胞体处流动（背根和同情 神经节）和神经纤维水平。 第二，评估 神经缺血性和再灌注损伤的分子机制 哪些信息完全缺乏。 神经是 由于缺血期间受损和由于相互作用而受损 将测试氧气自由基（OFR）和类黄花酱。 NBF， 计算机化视频学，血液障碍（BNB；至14C-） 蔗糖）和神经电生理指数将得到补充 通过估计神经胆固醇，花生四烯酸，脂肪酸 概况，丙二醛（MDA）和超氧化物歧化酶（SOD） 作为OFR损伤的指标和神经原位的生物合成 并且在血栓烷B2和6-Keto-Pfg1 alpha的体外将是 用作神经生叶的指标和神经儿茶酚胺 将测量。 这些研究将在缺血期间进行 再灌注后。 第三，对机制的评估 改善缺血和再灌注的影响。 钙 通道阻滞剂，血管扩张剂eiscosanoids，皮质类固醇，皮质类固醇， 五氧化苯丙胺和酮酸可能会改善微血管 其他组织中的缺血，但其机制和有效性 在周围神经中是未知的。 自缺血时间以来 纤维损伤非常缓慢，发生了多个小时，神经 包括一个特别适合干预疗法的系统 应该可以使用吗？ 最后，神经儿茶酚胺， eicosanoids，MDA和SOD将在Sural神经中测量 由于与本提案无关的原因而进行活检，以应用一些 这些技术和策略给人类。