Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, Kentucky 40536-0596, USA.
Alcohol Clin Exp Res. 2013 Mar;37(3):425-34. doi: 10.1111/j.1530-0277.2012.01955.x. Epub 2013 Jan 24.
Chronic intake of ethanol (EtOH) has been linked to serious health consequences such as cardiac and liver problems, cognitive impairments, and brain damage. Alcohol's detrimental effects depend upon the dose, duration, and pattern of exposure with binge drinking as one of the most common, but most damaging, patterns of intake. Little is known about the threshold of the damaging effects of alcohol. Therefore, these experiments sought to determine a threshold for brain damage using various markers of neurodegeneration.
Adult male Sprague-Dawley rats were administered nutritionally complete liquid diet containing either EtOH (25% w/v) or isocaloric dextrose every 8 hours for either 1 (mean dose, 13.4 ± 0.3 g/kg/d; mean blood EtOH concentration (BEC), 336.2 ± 18.8 mg/dl) or 2 days (mean dose, 10.9 ± 0.3 g/kg/d; mean BEC, 369.8 ± 18.1 mg/dl). On the basis of a known time course of various neurodegeneration-associated events, rats were perfused transcardially immediately following, 2 days after, or 7 days post EtOH exposure. To label actively dividing cells, some animals were injected with BromodeoxyUridine (BrdU) 2 hours prior to perfusion. Tissue was then analyzed for the presence of BrdU (cell proliferation), FluoroJade B (degenerative neurons), and vimentin (reactive astrogliosis) immunoreactivity.
One or 2 days of EtOH exposure failed to alter cell proliferation at any of the time points analyzed. However, significant 2- to 9-fold increases in neuronal degeneration in limbic cortex and clear evidence of reactive gliosis as indicated by a 2- to 8-fold upregulation in vimentin immunoreactivity in the hippocampus were observed following as little as 1 day of binge EtOH exposure.
These results indicate that as little as 1 day (24 hours) of high BEC, binge-like EtOH exposure is enough to elicit signs of alcohol-induced brain damage in adult rats. Further, reactive gliosis may be a more sensitive marker of alcohol-induced damage in the hippocampus.
慢性摄入乙醇（EtOH）与心脏和肝脏问题、认知障碍和脑损伤等严重健康后果有关。酒精的有害影响取决于剂量、持续时间和暴露模式， binge drinking 是最常见但最具破坏性的摄入模式之一。关于酒精造成损害的阈值知之甚少。因此，这些实验旨在使用各种神经退行性病变标志物来确定脑损伤的阈值。
成年雄性 Sprague-Dawley 大鼠给予含有营养完整的液体饮食，每 8 小时给予 EtOH（25%w/v）或等热量的右旋糖，持续 1（平均剂量为 13.4 ± 0.3 g/kg/d；平均血 EtOH 浓度（BEC）为 336.2 ± 18.8 mg/dl）或 2 天（平均剂量为 10.9 ± 0.3 g/kg/d；平均 BEC 为 369.8 ± 18.1 mg/dl）。基于各种与神经退行性病变相关事件的已知时程，在 EtOH 暴露后立即、2 天后或 7 天后经心灌注大鼠。为了标记活跃分裂的细胞，一些动物在灌注前 2 小时注射 BrdU。然后分析组织中 BrdU（细胞增殖）、FluoroJade B（变性神经元）和波形蛋白（反应性星形胶质增生）免疫反应性的存在。
1 或 2 天的 EtOH 暴露在任何分析的时间点均未改变细胞增殖。然而，在边缘皮层中观察到神经元变性显著增加 2 至 9 倍，并且在海马中波形蛋白免疫反应性增加 2 至 8 倍，表明存在明显的反应性神经胶质增生，这表明仅 1 天 binge EtOH 暴露就足以引起成年大鼠的酒精性脑损伤迹象。
这些结果表明，即使是 1 天（24 小时）的高 BEC、 binge-like EtOH 暴露也足以引起成年大鼠的酒精性脑损伤迹象。此外，反应性神经胶质增生可能是海马中酒精诱导损伤的更敏感标志物。
