Two recent paper s (Aspelund et al. 2015; Louveau et al.
2015) reported the presence in mice of lymphatics in the
cerebra l dura mater , the most external of the meningeal
layers covering the brain. This datum was reporte d as a
novel discovery in the \ufb01elds of neuroanatomy and neuroim-
munology

Bucchieri, F.

Cappello, F.

Farina, F.

Zummo, G.

PubMed

Two recent paper s (Aspelund et al. 2015; Louveau et al.
2015) reported the presence in mice of lymphatics in the
cerebra l dura mater , the most external of the meningeal
layers covering the brain. This datum was reporte d as a
novel discovery in the fields of neuroanatomy and neuroim-
munology

BUCCHIERI, Fabio

FARINA, Felicia

ZUMMO, Giovanni

CAPPELLO, Francesco

Archivio istituzionale della ricerca - Università di Palermo

MATTERS ARISINGLymphatic vessels of the dura mater: a new discovery?Fabio Bucchieri,1,2 Felicia Farina,1 Giovanni Zummo1 and Francesco Cappello1,21Human Anatomy Section, Department of Experimental Biomedicine and Clinical Neuroscience, University of Palermo,Palermo, Italy2Euro-Mediterranean Institute of Science and Technology, Palermo, ItalyKey words: blood–brain barrier; brain; central nervous system; dura mater; lymphatics; Mascagni;neuroanatomy; neuroimmunology; transudate.Dear Editor,Two recent papers (Aspelund et al. 2015; Louveau et al.2015) reported the presence in mice of lymphatics in thecerebral dura mater, the most external of the meningeallayers covering the brain. This datum was reported as anovel discovery in the fields of neuroanatomy and neuroim-munology. However, for the sake of clarity, we would liketo highlight the following issues:1. The presence of lymphatics in human dura mater hasalready been described by other authors: the first, toour knowledge, was Mascagni (1787) in his ‘Vasorumlymphaticorum corporis humani historia et ichono-graphia’ (Fig. 1). More recent reports (Lecco, 1953;Li et al. 1996) have also confirmed this historicobservation.2. The most recent studies (Aspelund et al. 2015; Lou-veau et al. 2015) did not confute the dogma thatlymphatics in the central nervous system (CNS) donot exist. In fact, dura mater is not a component ofthe neuraxis but covers, along with the othermeningeal layers, both the brain and the spinalcord.3. The so-called blood–brain barrier (BBB) (an anatomi-cal structure that, despite its name, is present in allparts of the neuraxis, with some small exceptions)prevents the formation of transudate (interstitialfluid) in the nervous tissue, thus preventing anychange in the volume of these structures that wouldinterfere with the functioning of the nervous cells;e.g. disruption of the BBB is the main cause of cere-bral oedema, a very severe pathological condition.As transudate does not form in the CNS, it is notnecessary to have any lymphatic vessel in this part ofthe human body.4. In the two most recent papers (Aspelund et al. 2015;Louveau et al. 2015), the experiments were per-formed on mice. Lecco (1953) examined the duramater of 30 human subjects and found lymphaticsstructures in four of them. Hence he concluded thatthese lymphatics probably developed in the duramater of these subjects for functional reasons, inde-pendently of the age of the subjects.5. Dural lymphatics, when present, can take part in theabsorption of cerebrospinal fluid (CSF), produced bythe choroid plexus, a dedicated region of the CNS cavi-ties (‘ventricles’) covered by ependymal cells, whichlack the BBB, and the formation of a transudate is aprerequisite for formation of this fluid. Lymphatic cellsmay migrate through the ependymal cell layer to theCSF, in turn reaching the dural lymphatics.We agree with the authors of the two most recent stud-ies (Aspelund et al. 2015; Louveau et al. 2015) who believethat a better knowledge of dural lymphatics can shedlight on the circulation of lymphatic cells from the arach-noid liquid to the venous bloodstream; and, as these cellsmay be a hallmark of disease, such as neuroinflammatoryor neurodegenerative pathologies, the study of these cellsmay open up new scenarios in the context of CNS diseasepathogenesis, early diagnosis, follow up and therapy. Wewould also like to thank the authors of both papers(Aspelund et al. 2015; Louveau et al. 2015) for havingdirected their attention to a sometimes forgotten chapterof human anatomy. However, in our opinion, their workhas not resulted in a new discovery, nor can they claimthat these lymphatics are present in the entire central ner-vous system, but only in its covering layers. We would liketo make these observations known for the benefit of ourstudents and colleagues.CorrespondenceFrancesco Cappello, Human Anatomy Section, Department of Experi-mental Biomedicine and Clinical Neuroscience, University of Palermo,Via alla Falconara 120, Palermo 90136, Italy. T: + 39 091 6553505;F: + 39 091 6553580; E: francapp@hotmail.comAccepted for publication 18 August 2015© 2015 Anatomical SocietyJ. Anat. (2015) doi: 10.1111/joa.12381Journal of AnatomyReferencesAspelund A, Antila S, Proulx ST, et al. (2015) A dural lymphaticvascular system that drains brain interstitial fluid and macro-molecules. J Exp Med 212, 991–999.Lecco V (1953) Di una probabile modificazione delle fissure lin-fatiche della della parte dei seni venosi della dura madre.Arch Ital Otol Rinol Laringol 64, 287–296.Li J, Zhou J, Shi Y (1996) Scanning electron microscopy ofhuman cerebral meningeal stomata. Ann Anat 178, 259–261.Louveau A, Smirnov I, Keyes TJ, et al. (2015) Structural andfunctional features of central nervous system lymphatic ves-sels. Nature 523, 337–341.Mascagni P (ed.) (1787) De lymphaticis profundis capitis et colli.Vasorum lymphaticorum corporis humani historia et ichno-graphia. Pars Prima Section VII, Art. VI. Siena: Pazzini Carli.Fig. 1 This picture shows the reproduction ofthe first page of the chapter of the book‘Vasorum lymphaticorum corporis humanihistoria et ichnographia’ in which PaoloMascagni first described the presence oflymphatics in the cerebral dura mater. Thearrow shows the incipit of the sentence inwhich Mascagni describes the course of theselymphatic vessels.© 2015 Anatomical SocietyMatters Arising2

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