EFFECT OF CHRONIC HYPOXIA ON BRAIN OXYGENATION

肌萎缩侧索硬化症（ALS）是一种神经退行性疾病， 主要影响运动神经元。 有两种形式 迄今为止发现的自发性疾病（90%的病例）， 家族性（10%的病例）。 在ALS的家族性形式中， 超氧化物歧化酶（SOD）基因存在突变， 约40%的患者。 几个假设解释 这些突变的重要性已经发表;然而，只有两个， 在本研究中将继续进行假设。 首先，它被认为 SOD的突变产生了功能的获得， 能够催化酪氨酸被过氧亚硝酸根硝化。 第二、 已经发现突变SOD中的铜更不稳定， 而游离铜可能有助于 疾病状态。 本项目将在 达特茅斯将涉及测定一氧化氮在小鼠的L-带 和X波段EPR光谱 最终目标是比较 Balb-C对照与转基因对照中金属和一氧化氮的量 小鼠，具有G93 A突变SOD基因的拷贝。 迄今为止 选择性神经毒素3-硝基丙酸，一种不可逆抑制剂 琥珀酸脱氢酶，已被用来刺激NO的生产， 大脑 在所有这些事件中都观察到了重大信号。 当NO被硫酸铁（II）捕获时， 二乙基二硫代氨基甲酸酯。 这被认为是第一个观察到的 完整小鼠内源性合成NO的EPR信号。

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease, mainly affecting the motor neurons. There are two forms of the disease recognized to date, spontaneous (90% of cases) and familial (10% of cases). In the familial form of ALS (FALS), there exists mutations in the superoxide dismutase (SOD) gene in approximately 40% of the patients. Several hypotheses explaining the significance of these mutations have been published; however, only two hypotheses will be pursued in this research. First, it is thought that the mutation in SOD produces a gain-of-function, perhaps being able to catalyse the nitration of tyrosine by peroxynitrite. Second, it has been found that the copper present in mutant SOD is more labile than that in wild-type, and that free copper may contribute to the disease state. The portion of this project to be conducted at Dartmouth will involve the assay of nitric oxide in mice with L-band and X-band EPR spectroscopy. The eventual goal is to compare the amount of metals and nitric oxide in Balb-C control versus transgenic mice, having copies of the G93A mutant SOD gene. To date, the selective neurotoxin 3-nitropropionic acid, an irreversible inhibitor of succinic dehydrogenase, has been used to stimulate NO production in the brain. Significant signals have been observed throughout all regions of the brain when NO is trapped by iron(II) sulfate and diethyl dithiocarbamate. This is believed to be the first observed EPR signal of endogenously synthesized NO in an intact mouse.