Jacob Asha, Wang Ping
Center for Immunology and Inflammation, The Feinstein Institutes for Medical Research, Northwell Health, Manhasset, NY, United States.
Department of Molecular Medicine, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, United States.
Front Neurosci. 2020 Feb 12;14:102. doi: 10.3389/fnins.2020.00102. eCollection 2020.
Binge alcohol drinking is highly prevalent in young adults and results in 30% deaths per year in young males. Binge alcohol drinking or acute alcohol intoxication is a risk factor for developing alcohol use disorder (AUD). Three FDA approved drugs are currently in use as therapy for AUD; however, all of them have contra-indications and limitations. Structural brain imaging studies in alcoholics have shown defects in the brain regions involved in memory, cognition and emotional processing. Positron emission tomography (PET) using radiotracers (e.g., FDG) and measuring brain glucose metabolism have demonstrated diagnostic and prognostic utility in evaluating patients with cognitive impairment. Using PET imaging, only a few exclusive human studies have addressed the relationship between alcohol intoxication and cognition. Those studies indicate that alcohol intoxication causes reduction in brain activity. Consistent with prior findings, a recent study by us showed that acute alcohol intoxication reduced brain activity in the cortical and subcortical regions including the temporal lobe consisting the hippocampus. Additionally, we have observed a strong correlation between reduction in metabolic activity and spatial cognition impairment in the hippocampus after binge alcohol exposure. We have also demonstrated the involvement of a stress response protein, cold inducible RNA binding protein (CIRP), as a potential mechanistic mediator in acute alcohol intoxication. In this review, we will first discuss in detail prior human PET imaging studies on alcohol intoxication as well as our recent study on acute alcohol intoxication, and review the existing literature on potential mechanisms of acute alcohol intoxication-induced cognitive impairment and therapeutic strategies to mitigate these impairments. Finally, we will highlight the importance of studying brain regions as part of a brain network in delineating the mechanism of acute alcohol intoxication-induced cognitive impairment to aid in the development of therapeutics for such indication.
暴饮酒精在年轻人中非常普遍，导致年轻男性每年有30%的死亡率。暴饮酒精或急性酒精中毒是发展成酒精使用障碍（AUD）的一个风险因素。目前有三种FDA批准的药物用于治疗AUD；然而，它们都有禁忌症和局限性。对酗酒者的结构性脑成像研究表明，参与记忆、认知和情绪处理的脑区存在缺陷。使用放射性示踪剂（如FDG）并测量脑葡萄糖代谢的正电子发射断层扫描（PET）已证明在评估认知障碍患者方面具有诊断和预后效用。使用PET成像，只有少数专门针对人类的研究探讨了酒精中毒与认知之间的关系。这些研究表明，酒精中毒会导致大脑活动减少。与先前的研究结果一致，我们最近的一项研究表明，急性酒精中毒会降低包括由海马体组成的颞叶在内的皮质和皮质下区域的大脑活动。此外，我们观察到暴饮酒精后海马体代谢活动的减少与空间认知障碍之间存在强烈的相关性。我们还证明了一种应激反应蛋白——冷诱导RNA结合蛋白（CIRP）作为急性酒精中毒潜在的机制介导物的参与。在这篇综述中，我们将首先详细讨论先前关于酒精中毒的人类PET成像研究以及我们最近关于急性酒精中毒的研究，并回顾关于急性酒精中毒诱导认知障碍的潜在机制和减轻这些障碍的治疗策略的现有文献。最后，我们将强调研究作为脑网络一部分的脑区在阐明急性酒精中毒诱导认知障碍机制以辅助开发此类适应症治疗方法方面的重要性。
