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冠状病毒:今日之挑战,呼吁扩大人类死后大脑分析。

Coronaviruses: a challenge of today and a call for extended human postmortem brain analyses.

机构信息

Clinic and Policlinic for Psychiatry, Psychosomatics and Psychotherapy, University Hospital Würzburg, Margarete-Hoeppel-Platz 1, 97080, Würzburg, Germany.

University of Southern Denmark Odense, J.B. Winslows Vey 18, 5000, Odense, Denmark.

出版信息

J Neural Transm (Vienna). 2020 Sep;127(9):1217-1228. doi: 10.1007/s00702-020-02230-x. Epub 2020 Jul 28.

Abstract

While there is abounding literature on virus-induced pathology in general and coronavirus in particular, recent evidence accumulates showing distinct and deleterious brain affection. As the respiratory tract connects to the brain without protection of the blood-brain barrier, SARS-CoV-2 might in the early invasive phase attack the cardiorespiratory centres located in the medulla/pons areas, giving rise to disturbances of respiration and cardiac problems. Furthermore, brainstem regions are at risk to lose their functional integrity. Therefore, long-term neurological as well as psychiatric symptomatology and eventual respective disorders cannot be excluded as evidenced from influenza-A triggered post-encephalitic Parkinsonism and HIV-1 triggered AIDS-dementia complex. From the available evidences for coronavirus-induced brain pathology, this review concludes a number of unmet needs for further research strategies like human postmortem brain analyses. SARS-CoV-2 mirroring experimental animal brain studies, characterization of time-dependent and region-dependent spreading behaviours of coronaviruses, enlightening of pathological mechanisms after coronavirus infection using long-term animal models and clinical observations of patients having had COVID-19 infection are calling to develop both protective strategies and drug discoveries to avoid early and late coronavirus-induced functional brain disturbances, symptoms and eventually disorders. To fight SARS-CoV-2, it is an urgent need to enforce clinical, molecular biological, neurochemical and genetic research including brain-related studies on a worldwide harmonized basis.

摘要

尽管有大量关于病毒引起的病理学的文献,特别是冠状病毒,但最近的证据表明,这种病毒会对大脑造成明显的有害影响。由于呼吸道与大脑相连,没有血脑屏障的保护,SARS-CoV-2 可能在早期侵袭阶段攻击位于延髓/脑桥区域的心肺中枢,导致呼吸和心脏问题。此外,脑干区域也有丧失功能完整性的风险。因此,不能排除长期的神经和精神症状以及最终的相应障碍,正如流感 A 引起的脑炎后帕金森病和 HIV-1 引起的艾滋病痴呆症所证明的那样。从目前关于冠状病毒引起的大脑病理学的证据来看,本综述得出了一些需要进一步研究的结论,如对人类死后大脑进行分析。SARS-CoV-2 可以模拟实验动物的大脑研究,阐明冠状病毒的时间依赖性和区域依赖性传播行为,利用长期动物模型和对患有 COVID-19 感染的患者的临床观察来揭示冠状病毒感染后的病理机制,这些都需要开发保护策略和药物发现,以避免早期和晚期冠状病毒引起的功能性大脑紊乱、症状和最终的障碍。为了对抗 SARS-CoV-2,迫切需要在全球范围内加强临床、分子生物学、神经化学和遗传学研究,包括与大脑相关的研究。

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