Fig. 3: Increases in intracranial pressure disrupt CNS lymphatic drainage.

a Measurements of intracranial pressure (ICP) and b representative pressure readings were collected at various time points after TBI (Sham n = 4, 30 min n = 6, 2 h n = 7, 6 h n = 4, 24 h n = 4, 3 days n = 5, 4 days n = 4, 1 week n = 4; pooled data from three independent experiments). c Representative images of internal jugular vein ligation (JVL). d ICP readings from mice that underwent bilateral JVL or a sham procedure 3 or 24 h prior (Sham n = 8, 3 h n = 6, 24 h n = 6; pooled data from three independent experiments). e–j The internal jugular vein was ligated bilaterally and then 0.5 μm fluorescent beads were injected i.c.m. 3 h later. dCLN and meninges were then harvested from mice 2 h after bead injection. e Representative images of dCLN and graph showing drainage of beads (f) 3 h and (g) 24 h after jugular venous ligation. Each data point represents an average of the 2 dCLNs from an individual mouse (3 h: Sham n = 10, JVL n = 10, 24 h: Sham n = 9, JVL n = 10; pooled data from two independent experiments). Solid boxes of the node images on the left show zoomed insets of the images on the right. h Representative images of meningeal whole-mounts with 0.5 μm beads (green) stained with DAPI (blue) and Lyve-1 660 (gray) and graph depicting percent area of bead coverage (i) 3 h and (j) 24 h post-JVL. Solid box shows a zoomed inset of the hotspot along the transverse sinus on the right (3 h: Sham n = 10, JVL n = 10, 24 h: Sham n = 9, JVL n = 10; pooled data from two independent experiments). All n values refer to the number of mice used and the error bars depict mean ± s.e.m. P values calculated by one-way ANOVA with Bonferroni’s multiple comparison test (a) and Tukey’s multiple comparison test (d) and two-tailed unpaired Student’s t-test (f, g, i, j). ICP intracranial pressure, JVL jugular venous ligation, h hour(s), min minute(s). Source data (a, d, f–g, i–j) are provided as a Source data file.