{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T04:47:12Z","timestamp":1791089232240,"version":"4.1.0"},"reference-count":34,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,9,19]],"date-time":"2023-09-19T00:00:00Z","timestamp":1695081600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006095","name":"Helse S\u00f8r-\u00d8st RHF","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006095","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:p><jats:bold>Background and purpose:<\/jats:bold> Previous experimental studies have shown that meningeal lymphatic vessels are located primarily along the walls of the dural sinus veins. Whether they are more widespread throughout human dura mater has presently not been characterized. The present study explored in humans whether meningeal lymphatic vessels may be identified remote from the sinus veins and whether they differ in the various location of dura mater.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> We included 15 patients who underwent neurosurgery, in whom dura mater was removed as part of the planned procedure. Tissue was prepared for immunohistochemistry using the lymphatic endothelial cell markers lymphatic vessel endothelial hyaluronan receptor 1 protein (LYVE-1), podoplanin and vascular endothelial growth factor receptor 3 (VEGFR3).<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> Lymphatic endothelial cell positive cells were found in dura mater at the posterior fossa (n = 8), temporal skull base (n = 5), frontal convexity (n = 1), and cranio-cervical junction (n = 1). They were most commonly seen remote from blood vessels, but also occurred along blood vessels, and seemed to be most abundant at the skull base.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> The present observations show that human lymphatic vessels are widespread in dura mater, not solely lining the dural sinuses.<\/jats:p>","DOI":"10.3389\/fcell.2023.1228344","type":"journal-article","created":{"date-parts":[[2023,9,20]],"date-time":"2023-09-20T04:33:39Z","timestamp":1695184419000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":23,"title":["Widespread distribution of lymphatic vessels in human dura mater remote from sinus veins"],"prefix":"10.3389","volume":"11","author":[{"given":"C\u00e9sar Luis","family":"Vera Quesada","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shreyas Balachandra","family":"Rao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reidun","family":"Torp","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Per Kristian","family":"Eide","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,9,19]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1038\/s41586-019-1419-5","article-title":"Meningeal lymphatic vessels at the skull base drain cerebrospinal fluid","volume":"572","author":"Ahn","year":"2019","journal-title":"Nature"},{"key":"B2","doi-asserted-by":"publisher","first-page":"991","DOI":"10.1084\/jem.20142290","article-title":"A dural lymphatic vascular system that drains brain interstitial fluid and macromolecules","volume":"212","author":"Aspelund","year":"2015","journal-title":"J. Exp. Med."},{"key":"B3","doi-asserted-by":"publisher","first-page":"2349","DOI":"10.1084\/jem.20062596","article-title":"Functionally specialized junctions between endothelial cells of lymphatic vessels","volume":"204","author":"Baluk","year":"2007","journal-title":"J. Exp. Med."},{"key":"B4","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1097\/moh.0000000000000711","article-title":"Meningeal Lymphatic vasculature in health and disease","volume":"29","author":"Bush","year":"2022","journal-title":"Curr. Opin. Hematol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"3159","DOI":"10.1038\/s41467-020-16851-z","article-title":"Meningeal lymphatics clear erythrocytes that arise from subarachnoid hemorrhage","volume":"11","author":"Chen","year":"2020","journal-title":"Nat. Commun."},{"key":"B6","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1038\/s41586-018-0368-8","article-title":"Functional aspects of meningeal lymphatics in ageing and Alzheimer's disease","volume":"560","author":"Da Mesquita","year":"2018","journal-title":"Nature"},{"key":"B7","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1038\/s41586-021-03489-0","article-title":"Meningeal lymphatics affect microglia responses and anti-A\u03b2 immunotherapy","volume":"593","author":"Da Mesquita","year":"2021","journal-title":"Nature"},{"key":"B8","doi-asserted-by":"publisher","first-page":"411","DOI":"10.1038\/s41591-020-01198-1","article-title":"Impaired meningeal lymphatic drainage in patients with idiopathic Parkinson's disease","volume":"27","author":"Ding","year":"2021","journal-title":"Nat. Med."},{"key":"B9","doi-asserted-by":"publisher","first-page":"e0196893","DOI":"10.1371\/journal.pone.0196893","article-title":"Borrelia burgdorferi adhere to blood vessels in the dura mater and are associated with increased meningeal T cells during murine disseminated borreliosis","volume":"13","author":"Divan","year":"2018","journal-title":"PloS one"},{"key":"B10","doi-asserted-by":"publisher","first-page":"7194","DOI":"10.1038\/s41598-018-25666-4","article-title":"Magnetic resonance imaging provides evidence of glymphatic drainage from human brain to cervical lymph nodes","volume":"8","author":"Eide","year":"2018","journal-title":"Sci. Rep."},{"key":"B11","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1002\/ar.1092300105","article-title":"The subdural space interpreted as a cellular layer of meninges","volume":"230","author":"Frederickson","year":"1991","journal-title":"Anat. Rec."},{"key":"B12","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1038\/s41422-020-0287-8","article-title":"Meningeal lymphatic vessels regulate brain tumor drainage and immunity","volume":"30","author":"Hu","year":"2020","journal-title":"Cell. Res."},{"key":"B13","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1227\/00006123-199301000-00017","article-title":"The \"subdural\" space: A new look at an outdated concept","volume":"32","author":"Haines","year":"1993","journal-title":"Neurosurgery"},{"key":"B14","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1038\/s41467-018-08163-0","article-title":"Neuroinflammation-induced lymphangiogenesis near the cribriform plate contributes to drainage of CNS-derived antigens and immune cells","volume":"10","author":"Hsu","year":"2019","journal-title":"Nat. Commun."},{"key":"B15","doi-asserted-by":"publisher","first-page":"e20220035","DOI":"10.1084\/jem.20220035","article-title":"Conserved meningeal lymphatic drainage circuits in mice and humans","volume":"219","author":"Jacob","year":"2022","journal-title":"J. Exp. Med."},{"key":"B16","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1186\/1743-8454-1-2","article-title":"Evidence of connections between cerebrospinal fluid and nasal lymphatic vessels in humans, non-human primates and other mammalian species","volume":"1","author":"Johnston","year":"2004","journal-title":"Cerebrospinal fluid Res."},{"key":"B17","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1186\/s40478-020-0888-y","article-title":"Subdural haematomas drain into the extracranial lymphatic system through the meningeal lymphatic vessels","volume":"8","author":"Liu","year":"2020","journal-title":"Acta neuropathol. Commun."},{"key":"B18","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1038\/nature14432","article-title":"Structural and functional features of central nervous system lymphatic vessels","volume":"523","author":"Louveau","year":"2015","journal-title":"Nature"},{"key":"B19","doi-asserted-by":"publisher","first-page":"1380","DOI":"10.1038\/s41593-018-0227-9","article-title":"CNS lymphatic drainage and neuroinflammation are regulated by meningeal lymphatic vasculature","volume":"21","author":"Louveau","year":"2018","journal-title":"Nat. Neurosci."},{"key":"B20","doi-asserted-by":"publisher","first-page":"1434","DOI":"10.1038\/s41467-017-01484-6","article-title":"Outflow of cerebrospinal fluid is predominantly through lymphatic vessels and is reduced in aged mice","volume":"8","author":"Ma","year":"2017","journal-title":"Nat. Commun."},{"key":"B21","doi-asserted-by":"publisher","first-page":"14974","DOI":"10.1038\/s41598-020-72031-5","article-title":"In vivo assessment of cerebrospinal fluid efflux to nasal mucosa in humans","volume":"10","author":"Melin","year":"2020","journal-title":"Sci. Rep."},{"key":"B22","doi-asserted-by":"publisher","first-page":"e2002574118","DOI":"10.1073\/pnas.2002574118","article-title":"An immunohistochemical study of lymphatic elements in the human brain","volume":"118","author":"Mezey","year":"2021","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B23","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1016\/j.nbd.2014.07.012","article-title":"Evidence for lymphatic A\u03b2 clearance in Alzheimer's transgenic mice","volume":"71","author":"Pappolla","year":"2014","journal-title":"Neurobiol. Dis."},{"key":"B24","doi-asserted-by":"publisher","first-page":"1723","DOI":"10.3171\/2010.12.Jns101732","article-title":"The collagenic architecture of human dura mater","volume":"114","author":"Protasoni","year":"2011","journal-title":"J. Neurosurg."},{"key":"B25","doi-asserted-by":"publisher","first-page":"354","DOI":"10.1038\/s41467-019-14195-x","article-title":"Cerebrospinal fluid tracer efflux to parasagittal dura in humans","volume":"11","author":"Ringstad","year":"2020","journal-title":"Nat. Commun."},{"key":"B26","doi-asserted-by":"publisher","first-page":"1464","DOI":"10.1093\/brain\/awab388","article-title":"Molecular trans-dural efflux to skull bone marrow in humans with CSF disorders","volume":"145","author":"Ringstad","year":"2022","journal-title":"Brain"},{"key":"B27","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1038\/s41586-022-05474-7","article-title":"Brain borders at the central stage of neuroimmunology","volume":"612","author":"Rustenhoven","year":"2022","journal-title":"Nature"},{"key":"B28","doi-asserted-by":"publisher","first-page":"538","DOI":"10.1038\/s41591-019-0417-3","article-title":"A (delayed) history of the brain lymphatic system","volume":"25","author":"Sandrone","year":"2019","journal-title":"Nat. Med."},{"key":"B29","doi-asserted-by":"publisher","first-page":"689","DOI":"10.1038\/s41586-019-1912-x","article-title":"VEGF-C-driven lymphatic drainage enables immunosurveillance of brain tumours","volume":"577","author":"Song","year":"2020","journal-title":"Nature"},{"key":"B30","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1186\/s12987-023-00426-3","article-title":"Immunohistochemical visualization of lymphatic vessels in human dura mater: methodological perspectives","volume":"20","author":"Vera Quesada","year":"2023","journal-title":"Fluids barriers CNS"},{"key":"B31","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1016\/j.neulet.2017.11.001","article-title":"Lymphatic vasculature in human dural superior sagittal sinus: implications for neurodegenerative proteinopathies","volume":"665","author":"Visanji","year":"2018","journal-title":"Neurosci. Lett."},{"key":"B32","doi-asserted-by":"publisher","first-page":"363","DOI":"10.1007\/s00401-018-1809-z","article-title":"The meninges as barriers and facilitators for the movement of fluid, cells and pathogens related to the rodent and human CNS","volume":"135","author":"Weller","year":"2018","journal-title":"Acta Neuropathol."},{"key":"B33","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1016\/s1286-0115(05)83235-7","article-title":"Microscopic morphology and histology of the human meninges","volume":"89","author":"Weller","year":"2005","journal-title":"Morphologie"},{"key":"B34","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1186\/s40035-019-0147-y","article-title":"Blocking meningeal lymphatic drainage aggravates Parkinson's disease-like pathology in mice overexpressing mutated alpha-synuclein","volume":"8","author":"Zou","year":"2019","journal-title":"Transl. Neurodegener."}],"container-title":["Frontiers in Cell and Developmental Biology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcell.2023.1228344\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,20]],"date-time":"2023-09-20T04:33:44Z","timestamp":1695184424000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcell.2023.1228344\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9,19]]},"references-count":34,"alternative-id":["10.3389\/fcell.2023.1228344"],"URL":"https:\/\/doi.org\/10.3389\/fcell.2023.1228344","relation":{},"ISSN":["2296-634X"],"issn-type":[{"value":"2296-634X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,9,19]]},"article-number":"1228344"}}