Fig. 5: Region-specific perivascular-independent transventricular, transleptomeningeal, and transependymal circulation of large CSF tracers.

a–b Gross (a) and histology (b) images of 15 nm gold nanoparticle (AuNP) (magenta) distribution 10 min, 30 min, and 4 h after intraventricular injection in P7 rodents. c 15 nm AuNP influx distance from the center of the olfactory bulb; rostral migratory stream; ependyma of the lateral ventricle medial wall (LV), ventral third ventricle (v3V), dorsal 3V (d3V); and floor of the fourth ventricle (4V) 10 minutes and 4 h post-intraventricular injection. Data are mean ± S.D., n = 3 rodents, unpaired two-tailed t-test. d Transependymal distance traveled by 15-nm AuNPs into the brain parenchyma from the LV medial wall compared to depth of penetration via influx from the dorsal convexity subarachnoid space 4 h post-intraventricular injection. Data are mean ± S.D., n = 3 rodents, unpaired two-tailed t-test. e–g Schematic (e), X-ray microtomography (XRM) (f), and histology (g) demonstrating transependymal 15 nm AuNP circulation through the medial (MW) and superior walls (SW) (black asterisks) and the subventricular zone (SVZ) (blue asterisk) of the right LV 4 h post-injection. There was very little 15 nm AuNP influx across the lateral wall (LW) lateral and inferior to the SVZ (red asterisk). Scalebars = 250 µm. Abbreviations: CP, caudate putamen; SVZ, subventricular zone; cg, cingulum; cc, corpus callosum; LS, lateral septal nucleus; MS, medial septal nucleus; df, dorsal fornix; LV, lateral ventricle; d3V, dorsal third ventricle; v3V, ventral third ventricle. h Higher magnification image of the right LV choroid plexus and MW. Scalebar = 50 µm. i Intraparenchymal distance traveled by 15 nm AuNPs from the LV MW, SW, and LW. Data are mean ± S.D., n = 3 rodents, one-way ANOVA with post hoc Tukey. j Histology and schematic showing 15 nm AuNP circulation into the hippocampus. scale bar = 500 µm, inset scalebar = 100 µm k Histology and schematic showing 15 nm AuNP influx into the hippocampus through the d3V (black asterisk) with sparse 15-nm AuNPs observed in the thalamus (red asterisk). scalebar = 1 mm. l 15 nm AuNP mean intensity in the hippocampus and thalamus. Data are mean± S.D., n = 3 rodents, unpaired two-tailed t-test d–l all observations and quantifications were made 4 h post-15 nm AuNP injection into the right LV across 3 rodents. Source data are provided in Supplementary Information. Figure 5e, j, and k were created with BioRender.com.