An immunohistochemical study of lymphatic elements in the human brain
| Autor: | Christopher T. Hogden, Péter Sótonyi, Eva Mezey, Ildiko Szalayova, Miklós Palkovits, Agnes Dosa, Alexandra Brady |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Central Nervous System
Male 0301 basic medicine T-Lymphocytes government.form_of_government Dura mater T cells Vesicular Transport Proteins cranial nerves CSF Antibodies Subarachnoid Space Lymphatic System 03 medical and health sciences 0302 clinical medicine Cell Movement meninges medicine Humans Perivascular space Aged Lymphatic Vessels Aged 80 and over Membrane Glycoproteins Multidisciplinary Pia mater business.industry Cranial nerves Meninges Brain Anatomy Biological Sciences Vascular Endothelial Growth Factor Receptor-3 Immunohistochemistry podoplanin Lymphatic Endothelium 030104 developmental biology medicine.anatomical_structure Lymphatic system government Female Autopsy Dura Mater Endothelium Lymphatic Subarachnoid space business Glymphatic System 030217 neurology & neurosurgery Neuroscience |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.2002574118 |
| Popis: | Significance The connection between brain and peripheral lymphatics has been studied for 250 y, mainly in animals. Specific markers for lymphatic endothelial cells (LECs) were discovered about a decade ago. We stained postmortem human brains with LYVE1 and PDPN to identify LECs. Marker-positive cells were found in membranes covering the brain, walls of vessels, and perivascular spaces, and among nerve fibers. These spaces also seem to contain T cells and are connected to peripheral lymphatics through passageways in the nasal cavity, optic nerve, and base of the skull. Our findings show a path that brain waste products take when they leave the central nervous system, paths that may be bidirectional. Almost 150 papers about brain lymphatics have been published in the last 150 years. Recently, the information in these papers has been synthesized into a picture of central nervous system (CNS) “glymphatics,” but the fine structure of lymphatic elements in the human brain based on imaging specific markers of lymphatic endothelium has not been described. We used LYVE1 and PDPN antibodies to visualize lymphatic marker-positive cells (LMPCs) in postmortem human brain samples, meninges, cavernous sinus (cavum trigeminale), and cranial nerves and bolstered our findings with a VEGFR3 antibody. LMPCs were present in the perivascular space, the walls of small and large arteries and veins, the media of large vessels along smooth muscle cell membranes, and the vascular adventitia. Lymphatic marker staining was detected in the pia mater, in the arachnoid, in venous sinuses, and among the layers of the dura mater. There were many LMPCs in the perineurium and endoneurium of cranial nerves. Soluble waste may move from the brain parenchyma via perivascular and paravascular routes to the closest subarachnoid space and then travel along the dura mater and/or cranial nerves. Particulate waste products travel along the laminae of the dura mater toward the jugular fossa, lamina cribrosa, and perineurium of the cranial nerves to enter the cervical lymphatics. CD3-positive T cells appear to be in close proximity to LMPCs in perivascular/perineural spaces throughout the brain. Both immunostaining and qPCR confirmed the presence of adhesion molecules in the CNS known to be involved in T cell migration. |
| Databáze: | OpenAIRE |
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