Mechanisms of Entry Into the Central Nervous System by Neuroinvasive Pathogens.
Mechanisms of Entry Into the Central Nervous System by Neuroinvasive Pathogens.
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DOI：
10.1097/wno.0000000000001455
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发表时间：
2022-06-01
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背景：关于 COVID-19 患者的神经系统表现、脑脊液分析和尸检的文献持续增加。所提出的 COVID-19 患者神经系统疾病的机制包括炎症、微血管损伤和缺氧缺血性损伤等间接过程。另一种假设表明，SARS-CoV-2 病毒直接进入大脑和脑脊液，鉴于有关从这些解剖部位分离病毒成分的不同报道。证据获取：手动搜索和审查了 PubMed、Google Scholar 数据库和神经解剖学教科书。结果：我们提供了有关病毒病原体侵入中枢神经系统 (CNS) 机制的临床概念；我们对众所周知的嗜神经病原体入侵中枢神经系统的机制理解的进展，有助于了解病毒如何进化进入脑实质的策略。我们还介绍了影响病毒进入的中枢神经系统区室的结构成分，重点关注血行和跨神经元传播，并讨论了这一证据，因为它与我们对严重急性呼吸综合征冠状病毒-2 (SARS-CoV-2)的理解有关。结论：尽管支持 SARS-CoV-2 病毒直接进入人类的数据很少，但增加我们对阻止病毒进入和病原体利用途径的中枢神经系统区室结构成分的了解，对于临床医生和研究人员做好准备至关重要。预期具有神经系统症状的新型病毒何时在中枢神经系统中建立感染，以及如何设计疗法来减轻这种感染。
Background:The literature on neurological manifestations, cerebrospinal fluid analyses, and autopsies in patients with COVID-19 continues to grow. The proposed mechanisms for neurological disease in patients with COVID-19 include indirect processes such as inflammation, microvascular injury, and hypoxic-ischemic damage. An alternate hypothesis suggests direct viral entry of SARS-CoV-2 into the brain and cerebrospinal fluid, given varying reports regarding isolation of viral components from these anatomical sites.Evidence Acquisition:PubMed, Google Scholar databases, and neuroanatomical textbooks were manually searched and reviewed.Results:We provide clinical concepts regarding the mechanisms of viral pathogen invasion in the central nervous system (CNS); advances in our mechanistic understanding of CNS invasion in well-known neurotropic pathogens can aid in understanding how viruses evolve strategies to enter brain parenchyma. We also present the structural components of CNS compartments that influence viral entry, focusing on hematogenous and transneuronal spread, and discuss this evidence as it relates to our understanding of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2).Conclusions:Although there is a paucity of data supporting direct viral entry of SARS-CoV-2 in humans, increasing our knowledge of the structural components of CNS compartments that block viral entry and pathways exploited by pathogens is fundamental to preparing clinicians and researchers for what to expect when a novel emerging virus with neurological symptoms establishes infection in the CNS, and how to design therapeutics to mitigate such an infection.