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: 3404597
• 负责人: PHILLIP A LOW
• 金额: $ 17.6万
• 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/3404597
• 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.

神经微血管在生理上是独特的，是一种很差的 大毛细血管的自动调节、营养电容系统 对缺血有相对的抵抗力。然而，血管病变 神经性疾病会发生，是相对常见的，很难 请客。神经缺血也可能发生在以下疾病中 糖尿病、水肿性和嵌顿性神经病。《博大》 这项延续提案的目的是加强对 神经缺血生理学。具体的目标、理论基础和 提出的方法有：第一，三维重建 神经病和脑缺血模型的神经血流量(NBF) 对交感神经刺激和去神经的反应。研究到 关于神经缺血的生理学研究数据一直以来 一维的，专注于神经干而忽略了很多 新陈代谢更活跃的细胞体和危险的远端轴突。通过 用微电极-H_2极谱和~(14)C-极谱相结合的方法 碘安替比林放射自显影，应该可以确定 同时在细胞体(背根和交感神经)流动 神经节)和神经纤维水平。第二，对中国经济发展的评价 大鼠神经缺血再灌注损伤的分子机制 而这些信息是完全缺乏的。神经是一种假设 在缺血和再灌流期间由于相互作用而受损 将测试氧自由基(OFR)和二十烷类化合物。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 通过测定神经胆固醇、花生四烯酸、脂肪酸 丙二醛(MDA)和超氧化物歧化酶(SOD) 作为氧自由基损伤和神经原位生物合成的指标 而在体外血栓烷B2和6-酮-PFG1α将 用作神经儿茶酚胺和神经儿茶酚胺的指标 将会被测量。这些研究将在缺血期和 再灌流后。第三，评估机制，以 改善脑缺血再灌流的作用。钙 通道阻滞剂，血管扩张剂等，皮质类固醇， 己酮可可碱和酮丝氨酸可改善微血管 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。由于脑缺血的时程 纤维损伤是非常缓慢的，发生在许多小时，神经 包括一个特别适合介入治疗的系统 如果它可用的话。最后，神经儿茶酚胺， 将测定腓肠神经中的二十碳化合物、丙二醛和超氧化物歧化酶。 出于与此无关的原因进行活组织检查，以应用一些 这些技术和策略对人类来说。