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.

神经微血管系统在生理上是独特的，是一个较差的 大毛细血管的自动调节、营养电容系统 也就是对缺血的抵抗力比较强。 然而血管病 神经病发生，相对常见且难以治疗 对待。 神经缺血也可能发生在以下疾病中： 糖尿病、水肿和卡压性神经病。 广义的 这一延续提案的目的是更加关注 神经缺血的生理学。 具体目标、理由和 提出的方法是：首先，3维重建 神经病缺血模型和神经血流（NBF） 对交感神经刺激和去神经支配的反应。 研究到 神经缺血生理学的最新进展 单维，关注神经干，忽略更多 代谢更活跃的细胞体和有风险的远端轴突。 经过 使用组合微电极-H2-极谱法和 14C- 碘安替比林放射自显影，应该可以确定 在细胞体（背根和交感神经）同时流动 神经节）和神经纤维水平。 二、评价 神经缺血再灌注损伤的分子机制 完全缺乏哪些信息。 假设神经是 缺血和再灌注期间由于相互作用而受损 将测试氧自由基 (OFR) 和类二十烷酸。 NBF, 计算机视频血管学、血神经屏障（BNB；至 14C- 补充蔗糖）和神经电生理指标 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 损伤和神经原位生物合成的指标 血栓素 B2 和 6-酮-PFG1 α 的体外实验将 用作神经二十烷酸和神经儿茶酚胺的指标 将被测量。 这些研究将在缺血期间进行 再灌注后。 三、评估机制 改善缺血和再灌注的影响。 钙 通道阻滞剂、血管扩张剂二十烷酸、皮质类固醇、 己酮可可碱和酮色林可能改善微血管 其他组织的缺血，但其机制和有效性 在周围神经中的作用尚不清楚。 由于缺血时间进程 纤维损伤非常缓慢，发生在几个小时内，神经 包括特别适合介入治疗的系统 如果它可用的话。 最后是神经儿茶酚胺， 将在腓肠神经中测量类二十烷酸、MDA 和 SOD 因与本提案无关的原因进行活检，以应用某些 这些技术和策略对人类来说。