The Biological Basis of Alcohol Induced Brain Damage

描述（由申请人提供）：长期慢性酒精滥用是 与大脑结构变化和神经认知障碍有关。 几 研究表明，这些现象之间存在令人信服的相关性， 似乎除了结构改变以外的神经基质 与酗酒和康复相关的认知变化。 的 本项目的总体目标是检验轴突/树突 以及白色物质中膜磷脂（可能还有灌注）的变化 与此相关的可逆性结构和神经认知变化的基础 长期慢性酒精滥用和康复。 受试者：50名轻度饮酒者 (LD)100个酒鬼 将在基线和9-12个月时研究LD 之后，HD将在进入酒精滥用治疗时进行研究（以捕获 由于大量饮酒造成的脑损伤的全部程度），在2-4周的 戒断，以及戒断期间进入治疗后9-12个月，或 复发 测量：通过神经心理学测试进行认知; MRI、轴突/树突和神经元活力（通过1H MR光谱成像） （N-乙酰天冬氨酸，一种假定的神经元/轴突标志物）;脂质， 含胆碱化合物（Cho）和肌醇（ml）以及磷-31 MRS（通过膜磷脂及其分解产物和前体）; 局部脑血流量将用探索性自旋标记测量 灌注MRI。 研究的具体重点将是白色物质，但 皮质和皮质下灰质，小脑，海马，体 胼胝体、脑干、颅内容积和各种脑容积 还将评估核。 我们预计，最初较低的区域NAA和 磷脂测量值和初始高Cho和mI测量值与 认知障碍的具体措施，这些结果的措施将 戒断期间恢复与认知改善相关;复发 会阻碍身体结构代谢和认知能力的提高 的 这些结果的意义有几个方面：首先，该项目将 开发非侵入性结果测量，提供客观定量 酒精引起的脑损伤的测量。 这在将来可能有用。 使用药物或治疗来减少饮酒的临床试验，或 监测旨在减少脑损伤或促进 复苏 其次，这些结果也可能提供信息， 发展出专门的药物治疗， 神经元或膜的损伤或促进恢复。

DESCRIPTION (Provided by applicant): Long-term chronic alcohol abuse is associated with structural brain changes and neuro-cognitive impairment. Few studies have shown a convincing correlation between these phenomena and it appears likely that neurosubstrates other than structural alterations underlie the cognitive changes associated with heavy drinking and recovery. The overall goal of this project is to test the hypothesis that axonal/dendritic and membrane phospholipid ( and possibly perfusion) changes in white matter underlie the reversible structural and neurocognitive changes associated with long-term chronic alcohol abuse and recovery. Subjects: 50 light drinkers (LD) and 100 heavy drinkers. LD will be studied at baseline and 9-12 months later, HD will be studied at entry into alcohol abuse treatment (to capture the full extent of brain damage due to heavy drinking), at 2-4 weeks of abstinence, and at 9-12 months after treatment entry during abstinence or relapse. Measurements: Cognition by neuropsychological testing; brain structures by MRI, axonal/dendritic and neuronal viability by 1H MR spectroscopic imaging (N-acetyl aspartate, a putative neuronal/axonal marker); lipids by choline-containing compounds (Cho) and myo-inositol (ml) and by phosphorus-31 MRS (via membrane phospholipids and their breakdown products and precursors); regional cerebral blood flow will be measured with exploratory spin-tagged perfusion MRI. The specific focus of the study will be on white matter, but cortical and subcortical gray matter, cerebellum, hippocampus, corpus callosum, and brain stem, intracranial volume and volumes of various brain nuclei will also be assessed. We expect that initially low regional NAA and phospholipid measures and initially high Cho and mI measures correlate with specific measures of cognitive impairment and that these outcome measures will recover during abstinence in association with cognitive improvements; relapse will arrest structural, metabolic, and cognitive improvements. The significance of these results is several fold: First, this project will develop non invasive outcome measures which provide objective quantitative measurements of alcohol-induced brain damage. This may be useful in future clinical trials in which drugs or treatments are used to reduce drinking, or to monitor effects of drugs aimed at reducing brain damage, or facilitating recovery. Second, these results may also provide information, which can lead to the development of specific drug treatments, aimed at preventing brain damage at the neuron or membrane or at facilitating recovery.