Objective: To provide independent validation in human dura obtained at autopsy of the reported presence of dural lymphatic vessels.

Background: Two recent studies have challenged the dogma that the brain is an immune privileged organ devoid of classical lymphatic drainage and described in mice the presence of functional lymphatic vessels lining the dural sinuses that drain both fluid and immune cells from the CSF to the deep cervical lymph nodes^{1, 2}. This exciting discovery has wide reaching implications for the etiology of neuroinflammatory and neurodegenerative proteinopathies including Parkinson’s disease, if these vessels are present in human dura as described to date in a single autopsy specimen.

Methods: Human dura mater at the level of the superior saggital sinus was collected at autopsy from a 77 year old male with no history of neurologic disease. Tissue was fixed in formalin, paraffin embedded and sectioned at 4 microns. Immunohistochemistry was performed for the lymphatic vessel endothelial cell marker podloplanin (mouse monoclonal antibody D2-40, Bio care medical at 1:100 dilution) using a OPTI-KIT in a Ventana Immunostainer. 

Results: Microscopic examination of the tissue revealed the presence of multiple podloplanin positive structures distributed throughout the superior saggital sinus. At high magnification there were several examples of podloplanin staining appearing to encircle a distinct lumen, suggesting the presence of vessel-like structures throughout the region.

Conclusions: We provide independent validation in human dura mater of the presence of structures with a vessel-like morphology that are positive for the lymphatic endothelial cell marker podloplanin. These vessels provide a putative infrastructure for drainage of macromolecules from the brain parenchyma and therefore represent an exciting avenue of exploration for involvement in the pathogenesis of neurodegenerative proteinopathies including Parkinson’s disease. 

References: 1.         Aspelund A, Antila S, Proulx ST, et al. A dural lymphatic vascular system that drains brain interstitial fluid and macromolecules. The Journal of experimental medicine 2015;212(7):991-999.

2.         Louveau A, Smirnov I, Keyes TJ, et al. Structural and functional features of central nervous system lymphatic vessels. Nature 2015;523(7560):337-341.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/dural-lymphatic-vasculature-in-human-superior-saggital-sinus-the-brain-drain/