Fig. 3

BBB disruption without tight junction impairment in SARS-CoV-2-infected animal models. a Representative images showing vessel leakage in the cortex of SARS-CoV-2-infected hamsters assessed by Evans blue dye (EBD), which emits red fluorescence under fluorescence microscopy. b Quantification of EBD in the tissues of hamsters (n = 3/group). c Ultrastructural images showing the destruction of basement membrane (BM) in the cortex after SARS-CoV-2 infection without obvious tight junction (TJ) damage. Red arrowhead: TJ. d Representative images showing Masson staining, immunohistochemical (IHC) staining for collagen IV and MMP9. Semi-quantitative analysis of area fraction of e collagen IV and f MMP9 staining measured by ImageJ software. g Relative mRNA levels of MMP9 in the brains of animal models. h Representative images showing immunostaining for TJ-related proteins, including claudin5, ZO-1, and occludin, and i histograms for their quantitative analysis. j Relative mRNA levels of claudin5, ZO-1, and occludin in the brains of animal models. N = 5–8 slices from three animals per group. The p-values were determined by a two-tailed unpaired Students’ t-test. *p < 0.01,**p < 0.01 vs. mock-treated group, respectively. Scale bar: a, d, h 100 μm