Excitotoxic Mechanisms in Alcoholic Brain Damage

长期酒精滥用导致的脑损伤局限于大脑的离散区域，并选择性地损害关键的神经心理功能。酒精滥用会影响控制大脑兴奋性的过程，导致脑细胞过度刺激。如果这种情况持续很长一段时间，细胞很可能会死亡，大多数酗酒者在成年后的大部分时间里都在滥用酒精。我们将研究人类大脑中被酒精选择性损伤的区域对谷氨酸的使用和反应能力，谷氨酸是大脑主要的天然刺激物。还将探讨这些能力如何受到遗传和通常与酗酒有关的疾病（如肝硬化）的影响。如果我们能弄清楚酗酒者的选择性脑损伤是如何发生的，我们就能更好地设计出新的药物疗法来对抗和预防它。此外，局部脑损伤是许多神经系统疾病的特征，因此该研究将提供疾病机制的一般模型。

Brain damage resulting from long-term alcohol abuse is localized to discrete regions of the brain and selectively impairs key neuropsychological functions. Alcohol misuse affects processes that control excitability in the brain, leading to the over-stimulation of brain cells. When this continues for long periods the cells are likely to die and most alcoholics misuse alcohol for most of their adult lives. We will study the human brain s capacity to use and respond to glutamate, its major natural excitant, in the regions that are selectively damaged by alcoholism. How these capacities are affected by heredity, and by diseases commonly associated with alcoholism such as cirrhosis of the liver, will also be explored. If we can understand how selective brain damage occurs in alcoholics we will be better able to devise new drug therapies to combat and prevent it. As well, localized brain damage is a feature of many neurological diseases, so the study will provide a general model of disease mechanisms.