The brain drainage system in 3D

Summary: CSF drainage pathways are similar between mice and humans, the researchers found.

Source: Yale

The meningeal lymphatic vessels are potential targets for treating brain diseases. The laboratories of Yale and the Institut du Cerveau de Paris (Hôpital Pitié-Salpêtrière, Paris) have imaged cerebral drainage by the meningeal lymphatics in mice and in humans.

The recent Journal of Experimental Medicine article 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 the Yale Cardiovascular Research Center (YCVRC), demonstrates that CSF drainage pathways are similar between mice and humans and reports a new MRI-based imaging technique for patients with neurological diseases.

The lymphatic vascular system controls immune surveillance and waste disposal in tissues and organs. The lymphatic vessels are absent from the central nervous system (CNS) but present at the borders of the CNS, in the meninges which protect the brain and the spinal cord. Meningeal lymphatic vessels drain into the lymph nodes of the neck and peripheral immune system, making them key players in the control of cerebral immunity.

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

The meningeal lymphatic system affects 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 is of great therapeutic interest,” explains Laurent Jacob, Ph.D., first author of the study and member of the Parisian research team.

“However, it remains unclear where lymphatic reuptake 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 studied CSF lymphatic drainage using post-mortem light sheet imaging in mice and CSF imaging. real-time magnetic resonance in humans. By combining these approaches, the authors reconstructed the entire CSF lymphatic drainage network.

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

This shows a 3D map of the brain's drainage system
The meningeal lymphatic vessels are potential targets for treating brain diseases. The image is credited to the researchers

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

Future research should explore whether these anatomical data are causally related to the greater predisposition of women to develop neurological diseases such as multiple sclerosis, meningiomas or intracranial hypertension.

“The meningeal lymph vessels are potential targets for treating brain disease,” Eichmann said. “Yale Laboratories are making progress toward elucidating their function by imagining cerebral drainage by meningeal lymphatics in mice and humans.”

About this neuroscience research news

Author: Elizabeth Reitman
Source: Yale
Contact: Elizabeth Reitman-Yale
Image: The image is attributed to the researchers

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Original research: Free access.
“Conserved meningeal lymphatic drainage circuits in mice and humans” by Laurent Jacob et al. Journal of Experimental Medicine


Conserved 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 waste disposal and immune surveillance of brain tissue. Whether MLVs exist in the anterior part of the murine and human skull and how they connect 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-A555 Cerebrospinal fluid (CSF) tracer injection and real-time magnetic resonance imaging (VW-MRI) of the vascular wall after systemic injection of gadobutrol in patients with neurological pathologies.

We observed a conserved three-dimensional anatomy of MLVs in mice and humans that aligned with the dural venous sinuses but not the CSF nasal discharge, and found an extensive anterior MLV network around the cavernous sinus, with exit routes through the foramina of the emissary veins. VW-MRI can provide a diagnostic tool for patients with CSF drainage defects and neurological diseases.

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