Fig. 4: Glial response and vascular damage after brain SARS-CoV-2 infection.
a–d, Representative images of Imaris 3D reconstruction of cortical (a) and hypothalamic (c) microglial cells from uninfected controls and SARS-CoV-2-infected mice (6 dpi) and quantitative morphological analysis of microglial cells in the cortex (b) and hypothalamus (d) showing total area, filament area and length and number of filament branching points. e–g, Quantification of the density of IBA1+ microglial cells (e) and GFAP+ astrocytes (f) in the cortex and hypothalamus and oligodendrocytes in the corpus callosum (g). h, High-magnification confocal images from control and SARS-CoV-2-infected K18-hACE2 mice stained with the vascular marker IB4 (red), showing the alterations observed in the brain vessels of SARS-CoV-2-infected animals. i, Analysis of the presence of abnormal blood vessels in the hypothalamus of controls and SARS-CoV-2-infected mice at 2, 4 and 6 dpi. In b,d,e,f,g,i, data are presented as the mean ± s.e.m. b,d, Representation of the individual microglial cell values from: control mice, n = 9 (4 females and 5 males); SARS-CoV-2-infected mice: 2 dpi, n = 8 (3 females and 5 males); 4 dpi, n = 8 (3 females and 5 males); and 6 dpi, n = 10 (5 females and 5 males). e–g, Control mice, n = 9 (4 females and 5 males (e,f)) and n = 8 (3 males and 5 males (g)); SARS-CoV-2-infected mice, 6 dpi, n = 9 (4 females and 5 males). i, Control mice, n = 9 (4 females and 5 males); SARS-CoV-2-infected mice: 2 dpi, n = 8 (3 females and 5 males); 4 dpi, n = 8 (3 females and 5 males); and 6 dpi, n = 10 (5 females and 5 males). Kruskal–Wallis test with post hoc Dunn’s test (b,d,i) and unpaired, two-sided t-test (e,f,g). In e,f: e, cortex: P = 0.001, hypothalamus: P < 0.0001; f, hypothalamus: P < 0.0001). **P < 0.01, ***P < 0.001, ****P < 0.0001 with regard to controls (uninfected mice).
