ArticleSignal transduction and targeted therapy2021
SARS-CoV-2 crosses the blood-brain barrier accompanied with basement membrane disruption without tight junctions alteration.
Article in Signal transduction and targeted therapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 179 papers.
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Who cites it
179 citing papers in PubMed, 300 citations in OpenAlex.
- Human brain matters: Navigating the neuropathology of COVID-19.Brain pathology (Zurich, Switzerland) · 2026Review
- Endothelial dysfunction: A central mechanism linking autosomal dominant polycystic kidney disease and intracranial aneurysms (Review).International journal of molecular medicine · 2026Review
- SARS-CoV-2 disrupts the integrity of a human blood-brain barrier model in the absence of infection.Journal of neurovirology · 2026Article
- Proteomic and Phosphoproteomic Characteristics of Multiple Brain Regions in Rhesus Macaques After SARS-CoV-2 Infection.MedComm · 2026Article
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- MRI of Syrian hamsters reveals SARS-CoV-2 variant-specific neuroinflammation.Microbiology spectrum · 2026Article
- Spatial multiomics dissects the SARS-CoV-2-induced disruption of cell adhesion and immune dynamics in the human hippocampus.Journal of neuroinflammation · 2026Article
- Mild chronic hypoxia and the brain: an ambiguous relationship.Journal of neuroinflammation · 2026Review
- Pathogenic breaches: how viruses compromise blood-tissue barriers.Tissue barriers · 2026Review
- SSRI/SNRI and long COVID in children and adolescents with neuropsychiatric conditions: a cohort study from the RECOVER Initiative.Nature. Mental health · 2026Article
- From HIV to SARS-CoV-2 associated neurological disorder ("HAND" to "SAND"): Viral infection as a "time-bomb" for the aging brain.Neuroscience applied · 2026Review
- SARS-CoV-2 spike S1-mediated HIF-2α activation in retinal endothelial cells suggests a mechanism contributing to post-COVID endothelial dysfunction.Frontiers in immunology · 2026Article
- Redox-Dependent Activation of Matrix Metalloproteinases Regulates Influenza A Virus Replication in Neuronal Cells.International journal of microbiology · 2026Article
- Coupling between neural oscillations and white matter integrity reveals cognitive computational profiles following COVID-19.Scientific reports · 2025Article
- The SARS-CoV-2 nucleocapsid protein induces microglia senescence-mediated cognitive impairment via Glycolysis.Molecular medicine (Cambridge, Mass.) · 2025Article
- Nanomaterials: an overview of current trends and future prospects in neurological disorder treatment.Journal of translational medicine · 2025Review
- Fatal Spontaneous Rebleeding of Subdural Haematoma Following COVID-19 Infection: A Case Report.Cureus · 2025Article
- Chronic Neuroplasticity Changes Following Neurotropic Viral Infection: Mechanisms and Implications.Cellular and molecular neurobiology · 2025Review
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119 more citing papers are in PubMed but not listed here.
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Authors and funding
21 authors at 1 institution in 1 country.
Funding
Abstract
SARS-CoV-2 has been reported to show a capacity for invading the brains of humans and model animals. However, it remains unclear whether and how SARS-CoV-2 crosses the blood-brain barrier (BBB). Herein, SARS-CoV-2 RNA was occasionally detected in the vascular wall and perivascular space, as well as in brain microvascular endothelial cells (BMECs) in the infected K18-hACE2 transgenic mice. Moreover, the permeability of the infected vessel was increased. Furthermore, disintegrity of BBB was discovered in the infected hamsters by administration of Evans blue. Interestingly, the expression of claudin5, ZO-1, occludin and the ultrastructure of tight junctions (TJs) showed unchanged, whereas, the basement membrane was disrupted in the infected animals. Using an in vitro BBB model that comprises primary BMECs with astrocytes, SARS-CoV-2 was found to infect and cross through the BMECs. Consistent with in vivo experiments, the expression of MMP9 was increased and collagen IV was decreased while the markers for TJs were not altered in the SARS-CoV-2-infected BMECs. Besides, inflammatory responses including vasculitis, glial activation, and upregulated inflammatory factors occurred after SARS-CoV-2 infection. Overall, our results provide evidence supporting that SARS-CoV-2 can cross the BBB in a transcellular pathway accompanied with basement membrane disrupted without obvious alteration of TJs.
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Registered trials
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