The brain’s drainage system in 3D

Overview: The CSF drainage pathways are similar between mice and humans, researchers found.

Source: Yalea

Meningeal lymphatics are potential targets for the treatment of brain diseases. Yale labs and the Paris Brain Institute (Pitié-Salpêtrière Hospital, Paris) have imaged brain drainage through meningeal lymphatics in mice and humans.

The recent Journal of Experimental Medicine paper led by Jean-Leon Thomas, Ph.D., professor of neurology, and Anne Eichmann, Ph.D., Ensign Professor of Medicine and professor of cellular and molecular physiology and co-director of Yale’s Cardiovascular Research Center (YCVRC), shows that CSF drainage pathways are similar between mice and humans and reports a novel MRI-based imaging technique for patients with neurological disorders.

The lymphatic vascular system controls the immune system’s surveillance and the elimination of waste products in tissues and organs. Lymphatics are absent from the central nervous system (CNS) but present at the CNS borders, in the meninges that protect the brain and spinal cord. The meningeal lymphatics flow to the lymph nodes of the neck and the peripheral immune system, making them important players in the control of brain immunity.

The meningeal lymphatics are also important for the elimination of wastes from the brain by participating in the clearance of interstitial fluid and soluble proteins, as well as the drainage of CSF which provides the brain with a protective fluid buffer against injury, a pathway for essential nutrients and a cellular waste disposal system.

The meningeal lymphatic system influences neurological diseases in many mouse models, including Alzheimer’s disease, multiple sclerosis, brain tumors and other conditions. “Because of its involvement in many diseases, the meningeal lymphatic system has generated a lot of therapeutic interest,” explains Laurent Jacob, Ph.D., lead author of the study and member of the Paris research team.

“However, it remained unclear where the lymphatic recapture of CSF molecules occurs in the context of the whole head, in mice or in humans.”

To learn more about the architecture and function of the meningeal lymphatic network, the team examined CSF lymphatic drainage using postmortem light-sheet imaging in mice and real-time magnetic resonance imaging in humans. By combining these approaches, the authors rebuilt the entire lymphatic drainage network of the CSF.

The 3D imaging showed that the meningeal lymphatics make contact with the venous sinuses of the dura mater, revealing an extensive meningeal lymphatic network surrounding the cavernous sinus in the anterior part of the skull. From there, meningeal lymphatics exit the skull through cranial foramina and drain to cervical lymph nodes.

This shows a 3D map of the brain's drainage system
Meningeal lymphatics are potential targets for the treatment of brain diseases. Image is credited to the researchers

Stéphanie Lenck, MD, also at Pitié-Salpêtrière Hospital, performed quantitative lymphatic MRI in 11 patients with various neurological disorders. She established a procedure for 3D visualization of all blood and lymphatic vasculature in the meninges and neck that revealed a significantly greater meningeal lymphatic volume in males than females.

Future research will have to determine whether these anatomical data are causally related to women’s greater predisposition to develop neurological diseases, such as multiple sclerosis, meningiomas or intracranial hypertension.

“Meningeal lymphatics are potential targets for treating brain diseases,” Eichmann said. “Yale labs are making progress in elucidating their function by imaging brain drainage through meningeal lymphatics in mice and humans.”

About this neuroscience research news

Author: Elisabeth Reitman
Source: Yalea
Contact: Elisabeth Reitman – Yalea
Image: The image is attributed to the researchers

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Original research: Open access.
“Preserved Meningeal Lymphatic Drainage Circuits in Mice and Humans” by Laurent Jacob et al. Journal of Experimental Medicine


Abstract

Preserved Meningeal Lymphatic Drainage Circuits in Mice and Humans

Meningeal lymphatic vessels (MLVs) have been identified in the dorsal and caudobasal regions of the dura mater, where they provide elimination of waste products and immune surveillance of brain tissues. Whether MLVs exist in the anterior portion of the mouse and human skull and how they are connected to the glymphatic system and extracranial lymphatics has remained unclear.

Here we used light-sheet fluorescence microscopy (LSFM) imaging of mouse whole head preparations after OVA-A.555 tracer injection into the cerebrospinal fluid (CSF) and performed real-time vessel wall (VW) magnetic resonance imaging (VW-MRI) after systemic injection of gadobutrol in patients with neurological pathologies.

We observed a conserved three-dimensional anatomy of MLVs in mice and humans aligned with dural venous sinuses but not with nasal CSF outflow, and we discovered an extensive anterior MLV network around the cavernous sinus, with exit pathways through the foramina of secreted veins. VW-MRI can be a diagnostic tool for patients with CSF drainage defects and neurological disorders.

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