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: 2702964
• 负责人: PHILLIP A LOW
• 金额: $ 18.98万
• 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 2000-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2702964
• 关键词: bioenergetics; blood flow measurement; eicosanoids; free radical oxygen; free radical scavengers; glucose metabolism; glucose transport; glutathione; hyperbaric oxygen therapy; hyperglycemia; indomethacin; induced hypothermia; ischemia; laboratory rat; microcapsule; nerve injury; neuroprotectants; nonhuman therapy evaluation; oxidative stress; peripheral nervous system; reperfusion; short chain fatty acid; tocopherols; vasomotion

DESCRIPTION (Investigator's Abstract): We will continue our studies on nerve ischemia. Based on preliminary results of neuroprotection by. hypothermia, hyperbaric oxygenation (HBO), and free radical scavengers, we will evaluate these 3 strategies, of peripheral nerve neuroprotection from ischemic fiber degeneration (IFD). The hypothesis is that hypothermic neuroprotection occurs because nerve, with its large energy stores and low metabolic rate, is able to survive on.anaerobic metabolism, provided that its energy requirements are further reduced by hypothermia. The first specific aim is to define the therapeutic window of hypothermic neuroprotection, in terms of the degree and duration of hypothermia, and the maximal tolerated delay. The second aim is to evaluate the mechanism of this protect,ion. To achieve this, we will undertake the following 5 studies. We will evaluate (1) the effect of hypothermia on nerve energy metabolism, and (2) on glucose utilization ( 14 C-deoxyglucose). (3) We will evaluate if enhancing glucose transport (dihyarolipoic acid) or (4) increasing endoneuriaI glucose, will enhance neuroprotection. (5) Finally, we will test the notion that hyperglycemia will enhance rather than reduce neuroprotection because the large endoneurial space adequately buffers changes in nerve lactate or protons. The third aim is to evaluate the efficacy of HBO as neuroprotection. The fourth aim is to evaluate the effects of altering oxidative stress on neuroprotection. Our approach is specifically relevant to nerve, and we will use agents that can be used clinically. We will inhibit the arachidonic acid cascade with indomethacin. Reduced glutathione will be administered because of nerves very low activity of glutathione and its enzymes. Finally, we will use probucol, a-tocopherol, and lipoic acid, three lipophilic aunts that stop lipid peroxidation and has been used clinically. The fifth aim is to continue our studies of nerve vasoregulation. We will study vasopressin, neuropeptide Y, and cilostazol (vasodilator and phosphodiesterase inhibitor on nerve blood flow.

描述（研究者摘要）：我们将继续研究 神经缺血基于神经保护的初步结果。 低温、高压氧（HBO）和自由基清除剂， 我们将评估这3种外周神经保护策略， 缺血性纤维变性（ischemic fiber degeneration，IFD）前提是 低温神经保护的发生是因为神经， 储存和低代谢率，是能够生存的。厌氧 代谢，前提是其能量需求进一步降低 体温过低第一个具体目标是确定治疗 低温神经保护的窗口，在程度和 低温持续时间和最大耐受延迟。第二个目的 评价这种保护作用的机制。因此我们 将开展以下5项研究。我们将评估（1）效果 低温对神经能量代谢的影响;（2）对葡萄糖的影响 利用率（14 C-脱氧葡萄糖）。(3)我们将评估是否加强 葡萄糖转运（二氢脂肪酸）或（4）增加神经内分泌 葡萄糖，将增强神经保护。(5)最后，我们将测试 认为高血糖会增强而不是降低 神经保护，因为大的神经内膜空间充分缓冲 神经乳酸或质子的变化。第三个目标是评估 HBO神经保护作用。第四个目标是评估 改变氧化应激对神经保护的影响。我们的方法 与神经有关，我们将使用可以 临床使用。我们将抑制花生四烯酸级联反应， 吲哚美辛将给予还原型谷胱甘肽，因为 神经谷胱甘肽及其酶活性很低。最后我们 将使用普罗布考，a-生育酚，和硫辛酸，三亲脂阿姨 阻止脂质过氧化作用并已被临床应用。第五个目标 就是继续我们对神经血管调节的研究我们将研究 加压素、神经肽Y和西洛他唑（血管扩张剂和 磷酸二酯酶抑制剂对神经血流量的影响。