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Recent work has shown that meningeal lymphatic vessels (mLVs), mainly in the dorsal part of the skull, are involved in the clearance of cerebrospinal fluid (CSF), but the precise route of CSF drainage is still unknown. Here we reveal the importance of mLVs in the basal part of the skull for this process by visualizing their distinct anatomical location and characterizing their specialized morphological features, which facilitate the uptake and drainage of CSF. Unlike dorsal mLVs, basal mLVs have lymphatic valves and capillaries located adjacent to the subarachnoid space in mice. We also show that basal mLVs are hotspots for the clearance of CSF macromolecules and that both mLV integrity and CSF drainage are impaired with ageing. Our findings should increase the understanding of how mLVs contribute to the neuropathophysiological processes that are associated with ageing.
It has been proposed that mLVs represent a vasculature that clears CSF and interstitial fluid (ISF) into the cervical lymph nodes (cLNs)1-8. These previous studies focused mainly on dorsal mLVs, which are located within dural folds along the superior sagittal sinus (SSS) and transverse sinus, and emphasized their functional importance1-6. However, although the drainage of exogenous tracers and T cells from the CSF into cLNs has been described1-5, dorsal mLVs do not take up and drain CSF tracers9. Indeed, mLVs in other parts of the CNS, such as lateral or basal parts of the skull (basal mLVs), have largely been unexplored. This is attributable to the fact that the skull base is an extremely complicated region that contains enormous bony structures and subarachnoid cisterns, as well as foramina that contain blood vessels and cranial nerves10,11, thus making it more difficult to study the lymphatic vessels of this area.
In this study, we successfully characterized the specialized morphologic features of basal mLVs in distinct locations by careful dissection of the skull base in mice. The basal mLVs revealed to be more suitable for CSF uptake and clearance compared with dorsal mLVs. Functional assessment of mLVs using CSF contrast-enhanced magnetic resonance imaging (MRI) and fluorescent imaging further revealed that basal mLVs are the major routes for CSF macromolecular uptake and drainage. Finally, we demonstrate that the basal mLVs undergo lymphedematous changes with age, which may be associated with the impaired...