3D-imaging reveals conserved cerebrospinal fluid drainage via meningeal lymphatic vasculature in mice and humans

Abstract

Meningeal lymphatic vessels (MLVs) contribute to waste product elimination and immune surveillance in brain tissues. MLVs were identified in the dorsal and caudo-basal regions of the dura mater, where they ensure the clearance of cerebrospinal fluid (CSF). Whether MLVs exist in the complex anterior part of the murine and human skull, and how they connect with the glymphatic system and extracranial lymphatic vasculature remained unclear. Here, we generated three-dimensional (3D) maps of MLV drainage by light-sheet fluorescence microscopy (LSFM) imaging of mouse whole-head preparations following fluorescent OVA-A555 tracer injections into the CSF. In humans, we performed real-time magnetic resonance vessel wall imaging (MR-VWI) after systemic gadobutrol injections. We observed a conserved 3D-anatomy of MLVs in mice and humans, and we discovered an extended anterior network around the dural cavernous sinus including multiple capillary beds and exit routes through the foramina of emissary veins. MR-VWI may provide a diagnostic tool for patients with CSF drainage defects and neurological diseases.

The Olfactory Organ Is a Unique Site for Neutrophils in the Brain

“…Similar to the tubular lymphatic described in the meninges, we observed a second lyve1b:EGFP + LV with tubular morphology similar to HEVs, in association with the OE/EN on the extracranial side of the cribriform plate localized to the distal tips of the LOE. These tubular LV have connections leading away from the region of the respiratory epithelia as has been described for mammals (79) and are severed during our dissections. Preliminary imaging suggests this LV extends across the face of the adult fish and terminates in a region posterior to the eye, and like the dorsal meningeal lymphatic network (78) may also be a candidate region for an (as-yet-undiscovered) analogue of cervical lymph nodes of mammals.…”

Demonstration of chemotherapeutic mediated lymphatic changes in meningeal lymphatics in vitro, ex vivo, and in vivo

“…We also observed differences in remodeling outcomes based on location of the lymphatic vessels. With the transverse sinus and superior sagittal sinus, recent studies noted differences of remodeling and functionality at the two different locations 19,[44][45][46] . There were no significant differences between the average number of branches and loops in terms of remodeling in both locations along the meningeal layer at the superior sagittal sinus.…”

Immune compartments at the brain’s borders in health and neurovascular diseases

“…Moreover, the subarachnoid space under the parietal bone, the most commonly used location for in vivo imaging, extends only 30-80 µm in a healthy mouse which renders it difficult to attribute cells under observation to a specific compartment [31]. Recent developments in whole body tissue clearing combined with light sheet fluorescent microscopy (vDISCO [32]) have the potential to overcome some of these limitations and similar techniques have been applied to study the vascular structure and bone development of the calvarium [33] and the meningeal lymphatic vasculature [34].…”