Fig. 7: VEGF-C treatment of aged mice results in decreased neuroinflammation after TBI.

Aged mice (18–20 months old) received 2 μl of artificial CSF containing 10¹³ genome copies per ml of either AAV1-CMV-mVEGF-C or control AAV1-CMV-eGFP by i.c.m. injection to rejuvenate meningeal lymphatic drainage function. Young mice (8–10 weeks of age) received 2 μl of artificial CSF containing 10¹³ genome copies per ml of control AAV1-CMV-eGFP by i.c.m. injection. Mice were rested for two weeks and then were subjected to either TBI or sham procedures. Two weeks after injury, brains were harvested, sectioned and stained for markers of gliosis. a) Representative image of a meningeal whole mount 1 month after viral vector administration showing Lyve-1 (gray), DAPI (blue), and AAV1-CMV-eGFP (green). b Righting times (Young-GFP + TBI n = 10, Aged-GFP + TBI n = 14, Aged-VEGFC + TBI n = 16; pooled data from two independent experiments) and c 10-point gross neuroscore of mice at 1 h after TBI (Young-GFP + TBI n = 9, Aged-GFP + TBI n = 14, Aged-VEGFC + TBI n = 16; pooled data from two independent experiments). d Representative images of hemisphere ipsilateral to the site of injury stained with Iba1 (gray), GFAP (red), and DAPI (blue). Dashed boxes in merge column indicate lesion site. e–h Quantification of the percent area of (e–f) Iba1 and (g–h) GFAP immunoreactivity in the hemispheres contralateral and ipsilateral to the site of injury. (Young-GFP + TBI n = 10, Aged-GFP + TBI n = 13, Aged-VEGFC + TBI n = 16; 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 Tukey’s multiple comparison correction (b, c, e, f, g, h). SSS superior sagittal sinus, TS transverse sinus. Source data (b–c, e–h) are provided as a Source data file.