Crews Fulton T, Nixon Kim
Bowles Center for Alcohol Studies, University of North Carolina, Chapel Hill, NC 27599, USA.
Alcohol Alcohol. 2009 Mar-Apr;44(2):115-27. doi: 10.1093/alcalc/agn079. Epub 2008 Oct 21.
This is a review of preclinical studies covering alcohol-induced brain neuronal death and loss of neurogenesis as well as abstinence-induced brain cell genesis, e.g. brain regeneration. Efforts are made to relate preclinical studies to human studies.
The studies described are preclinical rat experiments using a 4-day binge ethanol treatment known to induce physical dependence to ethanol. Neurodegeneration and cognitive deficits following binge treatment mimic the mild degeneration and cognitive deficits found in humans. Various histological methods are used to follow brain regional degeneration and regeneration.
Alcohol-induced degeneration occurs due to neuronal death during alcohol intoxication. Neuronal death is related to increases in oxidative stress in brain that coincide with the induction of proinflammatory cytokines and oxidative enzymes that insult brain. Degeneration is associated with increased NF-kappaB proinflammatory transcription and decreased CREB transcription. Corticolimbic brain regions are most sensitive to binge-induced degeneration and induce relearning deficits. Drugs that block oxidative stress and NF-kappaB transcription or increase CREB transcription block binge-induced neurodegeneration, inhibition of neurogenesis and proinflammatory enzyme induction. Regeneration of brain occurs during abstinence following binge ethanol treatment. Bursts of proliferating cells occur across multiple brain regions, with many new microglia across brain after months of abstinence and many new neurons in neurogenic hippocampal dentate gyrus. Brain regeneration may be important to sustain abstinence in humans.
Alcohol-induced neurodegeneration occurs primarily during intoxication and is related to increased oxidative stress and proinflammatory proteins that are neurotoxic. Abstinence after binge ethanol intoxication results in brain cell genesis that could contribute to the return of brain function and structure found in abstinent humans.
本文是一篇关于临床前研究的综述，内容涵盖酒精诱导的脑神经元死亡和神经发生丧失，以及戒酒诱导的脑细胞生成，即脑再生。旨在将临床前研究与人体研究联系起来。
所描述的研究是针对大鼠的临床前实验，采用已知会诱导对乙醇产生身体依赖的4天暴饮乙醇处理。暴饮处理后的神经退行性变和认知缺陷模拟了人类中发现的轻度退行性变和认知缺陷。使用各种组织学方法来追踪脑区的退行性变和再生。
酒精诱导的退行性变是由于酒精中毒期间的神经元死亡所致。神经元死亡与脑中氧化应激的增加有关，这与促炎细胞因子和氧化酶的诱导同时发生，而这些会损害大脑。退行性变与核因子-κB促炎转录增加和环磷腺苷反应元件结合蛋白（CREB）转录减少有关。皮质边缘脑区对暴饮诱导的退行性变最为敏感，并导致再学习缺陷。阻断氧化应激和核因子-κB转录或增加CREB转录的药物可阻断暴饮诱导的神经退行性变、神经发生抑制和促炎酶诱导。脑再生发生在暴饮乙醇处理后的戒酒期间。多个脑区出现增殖细胞爆发，戒酒数月后整个脑中有许多新的小胶质细胞，神经源性海马齿状回中有许多新的神经元。脑再生对于维持人类戒酒可能很重要。
酒精诱导的神经退行性变主要发生在中毒期间，与增加的氧化应激和具有神经毒性的促炎蛋白有关。暴饮乙醇中毒后的戒酒会导致脑细胞生成，这可能有助于恢复戒酒者的脑功能和结构。
