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An immunohistochemical study of lymphatic elements in the human brain
- Source :
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Year :
- 2021
- Publisher :
- Proceedings of the National Academy of Sciences, 2021.
-
Abstract
- 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.<br />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.
- Subjects :
- 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
Subjects
Details
- ISSN :
- 10916490 and 00278424
- Volume :
- 118
- Database :
- OpenAIRE
- Journal :
- Proceedings of the National Academy of Sciences
- Accession number :
- edsair.doi.dedup.....87b0dc3fd3395d7a0973487070feaf89