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    Home > Active Ingredient News > Study of Nervous System > The Qinchuan team discovered for the first time the molecular mechanism of the new coronavirus that can cross the blood-brain barrier and infect the brain

    The Qinchuan team discovered for the first time the molecular mechanism of the new coronavirus that can cross the blood-brain barrier and infect the brain

    • Last Update: 2021-10-02
    • Source: Internet
    • Author: User
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    Editor’s note iNature is China’s largest academic official account.
    It is jointly created by the doctoral team of Tsinghua University, Harvard University, Chinese Academy of Sciences and other units.
    The iNature Talent Official Account is now launched, focusing on talent recruitment, academic progress, scientific research information, interested parties can Long press or scan the QR code below to follow us
    .

    iNature reported that SARS-CoV-2 has the ability to invade the brains of humans and model animals
    .

    However, it is currently unclear whether and how SARS-CoV-2 crosses the blood-brain barrier (BBB)
    .

    On September 6, 2021, the Qin Chuan team from the Institute of Experimental Animals of the Chinese Academy of Medical Sciences published an online publication entitled "SARS-CoV-2 crosses the blood–brain barrier accompanied with basement membrane disruption without" in Signal Transduction and Targeted Therapy (IF=18.
    19).
    Tight junctions alteration" research paper, the study found that SARS-CoV-2 RNA was occasionally detected in the blood vessel wall and perivascular space and brain microvascular endothelial cells (BMEC) of infected K18-hACE2 transgenic mice
    .

    In addition, the permeability of the infected blood vessel increases
    .

    In addition, the disintegration of BBB was found in infected hamsters by administration of Evans blue
    .

    Interestingly, the expression of claudin5, ZO-1, occludin, and tight junction (TJ) ultrastructure did not change, while the basement membrane was destroyed in infected animals
    .

    Using an in vitro BBB model containing primary BMEC with astrocytes, it was found that SARS-CoV-2 was infected and passed through BMEC
    .

    Consistent with in vivo experiments, in SARS-CoV-2 infected BMEC, the expression of MMP9 increased, collagen IV decreased, and the TJ markers did not change
    .

    In addition, inflammatory response occurred after SARS-CoV-2 infection, including vasculitis, glial activation and up-regulation of inflammatory factors
    .

    Overall, the results of the study provide evidence that SARS-CoV-2 can cross the BBB through a transcellular pathway, while the basement membrane is destroyed without significant changes in TJ
    .

    Nervous system manifestations are frequently reported in patients infected with SARS-CoV-2, including headaches, olfactory disturbances, dysgeusia, disturbances of consciousness, seizures, strokes, and vascular events
    .

    New evidence shows that SARS-CoV-2 can infect the central nervous system (CNS) in addition to the respiratory system
    .

    Huber and colleagues have detected SARS-CoV-2 RNA in multiple organs, including the postmortem brain tissue of COVID-19 patients
    .

    A recent study of COVID-19 patients after autopsy showed that SARS-CoV-2 is present in cortical neurons
    .

    In addition, the results from human brain organoids also prove the neural invasion ability of SARS-CoV-2.
    Together, these data provide evidence for SARS-CoV-2 infection in the human central nervous system, but how the virus enters the brain is unclear.
    unknown
    .

    Studies have shown that SARS-CoV-2 virus may spread from peripheral retrograde axons to the central nervous system through olfactory sensory neurons (or other nerve bundles)
    .

    However, there is currently no convincing evidence, and in COVID-19, the olfactory nerve is a possible route of brain infection is still controversial
    .

    In addition to the possibility of invading the central nervous system through the olfactory route, SARS-CoV-2 may enter the brain through the blood route
    .

    According to reports, SARS-CoV-2 can infect choroid plexus epithelial cells in human brain organoids, and the blood-cerebrospinal fluid barrier (BCSFB) may be the entrance of SARS-CoV-2 into the central nervous system
    .

      The blood-brain barrier (BBB) ​​is mainly formed by endothelial cells and is another major barrier that restricts pathogens (including viruses or virus-infected cells) from entering the central nervous system from the systemic circulation
    .

    Interestingly, Meinhardt et al.
    observed the SARS-CoV-2 spike protein (S) in small CNS vascular endothelial cells of patients with COVID-19 by immunostaining
    .

    The use of intravenous radioiodination showed that the S1 protein of SARS-CoV-2 passed through the BBB of mice through adsorptive transcytosis
    .

    It has recently been demonstrated that SARS-CoV-2 S protein can alter the BBB function and reduce BBB integrity in 2D static and 3D microfluidic in vitro models
    .

    However, there is no direct evidence that live SARS-CoV-2 can cross the BBB, and how the virus crosses the BBB is still unresolved
    .

    Here, the study used pathological techniques, including fluorescence in situ hybridization (FISH), transmission electron microscopy (TEM), and immunostaining to prove that SARS-CoV-2 may be caused by direct BMEC infection and MMP9-mediated destruction of basement membrane Passing through the BBB does not affect the tight connection between the body and the body
    .

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