Human and nonhuman primate meninges harbor lymphatic vessels that can be visualized noninvasively by MRI

Author:

Absinta Martina1ORCID,Ha Seung-Kwon1ORCID,Nair Govind1ORCID,Sati Pascal1,Luciano Nicholas J1,Palisoc Maryknoll2,Louveau Antoine3,Zaghloul Kareem A4ORCID,Pittaluga Stefania2,Kipnis Jonathan3,Reich Daniel S1ORCID

Affiliation:

1. Translational Neuroradiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, United States

2. Hematopathology Section, Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, United States

3. Center for Brain Immunology and Glia, Department of Neuroscience, School of Medicine, University of Virginia, Charlottesville, United States

4. Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, United States

Abstract

Here, we report the existence of meningeal lymphatic vessels in human and nonhuman primates (common marmoset monkeys) and the feasibility of noninvasively imaging and mapping them in vivo with high-resolution, clinical MRI. On T2-FLAIR and T1-weighted black-blood imaging, lymphatic vessels enhance with gadobutrol, a gadolinium-based contrast agent with high propensity to extravasate across a permeable capillary endothelial barrier, but not with gadofosveset, a blood-pool contrast agent. The topography of these vessels, running alongside dural venous sinuses, recapitulates the meningeal lymphatic system of rodents. In primates, meningeal lymphatics display a typical panel of lymphatic endothelial markers by immunohistochemistry. This discovery holds promise for better understanding the normal physiology of lymphatic drainage from the central nervous system and potential aberrations in neurological diseases.

Funder

National Institute of Neurological Disorders and Stroke

National Multiple Sclerosis Society

Conrad N. Hilton Foundation

National Cancer Institute

National Institute on Aging

Lymphatic Education and Research Network

Publisher

eLife Sciences Publications, Ltd

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience

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