Mechanisms of Entry Into the Central Nervous System by Neuroinvasive Pathogens

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Title Mechanisms of Entry Into the Central Nervous System by Neuroinvasive Pathogens
Creator Navid Valizadeh; Emily A. Rudmann; Isaac H. Solomon; Shibani S. Mukerji
Affiliation Division of Neuroimmunology and Neuro-infectious Disease (NV, ER, SSM), Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts; John C Lincoln Hospital (NV), Phoenix, Arizona; Harvard Medical School (ER, IHS, SSM), Boston, Massachusetts; and Department of Pathology (IHS), Brigham and Women's Hospital, Boston, Massachusetts
Abstract 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.
Subject Brain; COVID-19; Central Nervous System; Nervous System Diseases; SARS-CoV-2
OCR Text Show
Date 2022-06
Language eng
Format application/pdf
Type Text
Publication Type Journal Article
Source Journal of Neuro-Ophthalmology, June 2023, Volume 43, Issue 2
Collection Neuro-Ophthalmology Virtual Education Library: Journal of Neuro-Ophthalmology Archives: https://novel.utah.edu/jno/
Publisher Lippincott, Williams & Wilkins
Holding Institution Spencer S. Eccles Health Sciences Library, University of Utah
Rights Management © North American Neuro-Ophthalmology Society
ARK ark:/87278/s6dfgbe9
Setname ehsl_novel_jno
ID 2307893
Reference URL https://collections.lib.utah.edu/ark:/87278/s6dfgbe9
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