NERVE BLOOD FLOW IN NORMAL AND ISCHEMIC PERIPHERAL NERVE

神经微血管在生理上是独特的， 大毛细血管的自动调节营养容系统 对局部缺血有相对的抵抗力。 但血管病 神经病变的发生，是相对常见的，并且难以 请客 神经缺血也可能发生在诸如以下的病症中： 糖尿病、水肿和压迫性神经病。 广大 这一延续建议的目的是加强对 神经缺血生理学 具体目标、理由和 提出的方法是：首先，三维重建的 在神经病变的缺血模型和神经病变的缺血模型中， 对交感神经刺激和去神经支配的反应。 研究来 关于神经缺血生理学的数据 单维的，只关注神经干而忽略了 代谢更活跃的细胞体和处于危险中的远端轴突。 通过 使用组合微电极-H2-极谱法和14 C- 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，评价 神经缺血再灌注损伤的分子机制 这是完全缺乏的信息。 假设神经是 在缺血和再灌注期间由于以下因素的相互作用而受损： 将测试氧自由基（OFR）和类二十烷酸。 NBF， 计算机视频血管造影，血神经屏障（BNB;至14 C- 蔗糖）和神经电生理指标进行补充 通过神经胆固醇、花生四烯酸、脂肪酸 丙二醛（MDA）和超氧化物歧化酶（SOD） 作为OFR损伤和原位神经生物合成的指标 血栓素B2和6-酮-PFG 1 α的体外试验将 用作神经类石杉酯碱和神经类儿茶酚胺的指标 将被衡量。 这些研究将在缺血期间进行， 再灌注后。 第三，评估各种机制， 改善缺血再灌注损伤。 钙 通道阻滞剂，血管扩张剂类二十二烷，皮质类固醇， 喷替茶碱和酮色林可改善微血管 其他组织缺血，但其机制和有效性 周围神经损伤的情况尚不清楚。 由于缺血性心脏病的时间进程 纤维损伤是非常缓慢的，发生在许多小时，神经 包括特别适合于介入治疗的系统 如果它可用的话。 最后，神经儿茶酚胺， 测定腓肠神经中的类花生酸、MDA和SOD 活检的原因无关，这一建议适用于一些 这些技术和策略。

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.