Laboratory of CNS injury and Molecular Therapy, JFK Neuroscience Institute, Hackensack Meridian Health JFK University Medical Center, 65 James St, Edison, NJ 08820, United States; Department of Neurology, Hackensack Meridian School of Medicine, Nutley, NJ 07110, USA.
Laboratory of CNS injury and Molecular Therapy, JFK Neuroscience Institute, Hackensack Meridian Health JFK University Medical Center, 65 James St, Edison, NJ 08820, United States.
Exp Neurol. 2022 Dec;358:114222. doi: 10.1016/j.expneurol.2022.114222. Epub 2022 Sep 9.
After a mild traumatic brain injury (mTBI), victims often experience emotional/psychological stress such as heightened irritability, anxiety, apathy, and depression. Severe mental health complications are common in military populations following a combat-acquired TBI and intensified unhealthy alcohol use. The high prevalence of alcohol abuse among TBI victims underscores how alcohol abuse exacerbates emotional/psychological symptoms such as depression and anxiety. The experimental mTBI was induced in vivo by fluid percussion injury (15 psi) in mice and ethanol diet feeding continued for 28 days. We analyzed different biomarkers of the biochemical mechanisms and pathophysiology of neurological damage, and functional outcome of psychological stress by sucrose preference, and light-dark tests. We demonstrated that the synergistic effect of TBI and alcohol leads to psychological stress such as depression and anxiety. The studies showed that oxidative stress, amyloidogenesis, tau pathology, neuroinflammation, and neurodegeneration markers were elevated, and glial activation and blood-brain barrier (BBB) damage were exacerbated during the synergistic effect of TBI and alcohol. Further, we studied the biochemical mechanisms of psychological stress that showed the significant reduction of 5-HT1AR, neuropeptide-Y, and norepinephrine, and an increase in monoamine oxidase-a in the combined effect of TBI and alcohol. This work suggested that the combined TBI and alcohol-induced effect leads to depression and anxiety, via sequential biochemical changes that cause neuroinflammation, amyloidogenesis, tau pathology, neurodegeneration, and BBB alterations. This clinically relevant study will contribute to developing a comprehensive therapeutic approach for patients suffering from TBI and alcohol-mediated neurological damage and psychological stress.
轻度创伤性脑损伤（mTBI）后，患者常经历情绪/心理应激，如易激惹、焦虑、淡漠和抑郁加重。在军事人群中，创伤性脑损伤后严重的精神健康并发症和强化的不健康饮酒很常见。创伤性脑损伤患者中酒精滥用的高患病率强调了酒精滥用如何加剧抑郁和焦虑等情绪/心理症状。体内通过流体冲击损伤（15psi）在小鼠中诱导实验性 mTBI，并继续进行乙醇饮食喂养 28 天。我们分析了神经损伤的生化机制和病理生理学以及心理应激的功能结果的不同生物标志物，通过蔗糖偏好和明暗测试。我们证明了 TBI 和酒精的协同作用导致抑郁和焦虑等心理应激。这些研究表明，氧化应激、淀粉样蛋白形成、tau 病理学、神经炎症和神经退行性变标志物升高，在 TBI 和酒精的协同作用下，胶质细胞激活和血脑屏障（BBB）损伤加剧。此外，我们研究了心理应激的生化机制，表明在 TBI 和酒精的联合作用下，5-HT1AR、神经肽 Y 和去甲肾上腺素显著减少，单胺氧化酶-a 增加。这项工作表明，TBI 和酒精联合作用导致抑郁和焦虑，通过引起神经炎症、淀粉样蛋白形成、tau 病理学、神经退行性变和 BBB 改变的连续生化变化。这项具有临床相关性的研究将有助于为患有 TBI 和酒精介导的神经损伤和心理应激的患者开发综合治疗方法。
