EFFECT OF CHRONIC HYPOXIA ON BRAIN OXYGENATION

肌萎缩侧索硬化症是一种神经退行性疾病 疾病，主要影响运动神经元。有两种形式的 迄今已认识到的疾病，自发性(90%的病例)和 家族性(10%)。家族性肌萎缩侧索硬化症(FALS) 存在超氧化物歧化酶(SOD)基因突变 大约40%的患者。以下几个假设解释了 这些突变的意义已经发表；然而，只有两个 在这项研究中，假设将继续下去。首先，人们认为 超氧化物歧化酶的突变会产生一种功能增强，可能是 能够催化过亚硝酸根硝化酪氨酸。第二, 已经发现，突变的超氧化物歧化酶中存在的铜更不稳定 而游离态的铜可能对 疾病状态。这一项目的部分将在 达特茅斯将参与L波段小鼠一氧化氮的测定 和X波段电子顺磁共振波谱。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含量 小鼠，具有G93A突变的SOD基因的副本。到目前为止， 选择性神经毒素3-硝基丙酸，一种不可逆的抑制剂 琥珀酸脱氢酶，已被用来刺激一氧化氮的产生 大脑。在整个过程中观察到了显著的信号 当NO被硫酸铁捕获时的大脑区域 二硫代氨基甲酸二乙酯。这被认为是第一次观察到 正常小鼠内源性合成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.