Fig. 3.

The outflow of meningeal lymphatics in mice and humans. a In mice, on in vivo fluorescent microscopy and ex vivo histologic studies, zipper-like junctions in the young and button-like junctions are differentially found in dorsal (SSS: superior sagittal sinus, TS: transverse sinus) and in basal (SS: sigmoid sinus, PSS: petrosquamosal sinus), respectively. Aging resulted in hyperplasia, impaired valves, and disrupted junctions. PSF petrosquamous fissure, SMF stylomastoid foramen, JF jugular foramen. Reprinted with permission from Ahn et al. [27]. b After intrathecal injection of gadodiamide, at 15 h, putative meningeal lymphatic vessels were visualized on these 3D CUBE-T2-FLAIR MRI images. Unenhanced superior sagittal sinuses (white arrows) were surrounded by putative meningeal lymphatic vessels. Reprinted with permission from Zhou et al. [22]. c On stereomicroscope in Prox1-GFP mice after intraventricular injection of infrared pegylated dye (40 kDa), the outflow of CSF was found to reach mandibular (superficial cervical) and deep cervical lymph nodes within an hour. The flow was followed through lymphatic vessels and shown as arrowheads on this schematic drawing. Reprinted with permission from Ma et al. [30]. d On T2 FLAIR MRI, TOF angiography was done to reveal the direction of the flow, saturation band posterior to the image section showed bright signal in superior sagittal sinus due to influx of unsaturated venous blood from anterior to posterior direction (left image; yellow arrowhead). In reverse, the saturation band anterior to the image section showed an expected low signal but the white signal in meningeal lymphatic vessels (right image: blue arrow). Countercurrent lymphatic flow from posterior to anterior compared with the venous flow was concluded in humans. Reprinted with permission from Absinta et al. [35]