SARS-CoV-2 crosses the blood-brain barrier accompanied with basement membrane disruption without tight junctions alteration.
Signal Transduct Target Ther
; 6(1): 337, 2021 09 06.
Article
in English
| MEDLINE | ID: covidwho-1402050
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.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Basement Membrane
/
Blood-Brain Barrier
/
Tight Junctions
/
SARS-CoV-2
/
COVID-19
Type of study:
Randomized controlled trials
Limits:
Animals
/
Humans
Language:
English
Journal:
Signal Transduct Target Ther
Year:
2021
Document Type:
Article
Affiliation country:
S41392-021-00719-9
Similar
MEDLINE
...
LILACS
LIS