Butterworth R F
Neuroscience Research Unit, Hôpital Saint-Luc (University of Montreal), Quebec, H2X 3J4 Canada.
Metab Brain Dis. 1995 Mar;10(1):1-8. doi: 10.1007/BF01991777.
Chronic alcoholism results in brain damage and dysfunction leading to a constellation of neuropsychiatric symptoms including cognitive dysfunction, the Wernicke-Korsakoff Syndrome, alcoholic cerebellar degeneration and alcoholic dementia. That these clinically-defined entities result from independent pathophysiologic mechanisms is unlikely. Alcohol and its metabolite acetaldehyde are directly neurotoxic. Alcoholics are thiamine deficient as a result of poor diet, gastrointestinal disorders and liver disease. In addition, both alcohol and acetaldehyde have direct toxic effects on thiamine-related enzymes in liver and brain. Alcoholics frequently develop severe liver disease and liver disease per se results in altered thiamine homeostasis, in cognitive dysfunction and in neuropathologic damage to astrocytes. The latter may result in the loss of neuron-astrocytic trafficking of neuroactive amino acids and thiamine esters, essential to CNS function. The present review article proposes mechanisms whereby the effects of alcohol, thiamine deficiency and liver disease combine synergistically to contribute to the phenomena of cognitive dysfunction and "alcoholic brain damage".
慢性酒精中毒会导致脑损伤和功能障碍，进而引发一系列神经精神症状，包括认知功能障碍、韦尼克-科尔萨科夫综合征、酒精性小脑变性和酒精性痴呆。这些临床定义的病症不太可能由独立的病理生理机制导致。酒精及其代谢产物乙醛具有直接神经毒性。由于饮食不良、胃肠道疾病和肝脏疾病，酗酒者会出现硫胺素缺乏。此外，酒精和乙醛对肝脏和大脑中与硫胺素相关的酶都有直接毒性作用。酗酒者经常会患上严重的肝脏疾病，而肝脏疾病本身会导致硫胺素稳态改变、认知功能障碍以及星形胶质细胞的神经病理损伤。后者可能导致对中枢神经系统功能至关重要的神经活性氨基酸和硫胺素酯的神经元 - 星形胶质细胞转运丧失。本综述文章提出了酒精、硫胺素缺乏和肝脏疾病的影响协同作用导致认知功能障碍和“酒精性脑损伤”现象的机制。
