The drainage system of the brain in 3D

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

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Meningeal lymphatic vessels are potential targets for treating brain diseases. Yale Laboratories and the Paris Brain Institute (Pitié-Salpêtrière Hospital, Paris) have imaged brain drainage by meningeal lymphatic vessels in mice and humans.

the recent Journal of Experimental Medicine article led by Jean-Leon Thomas, Ph.D., professor of neurology, and Anne Eichmann, Ph.D., professor of medicine and professor of molecular and cellular physiology and co-director of the Yale Cardiovascular Research Center (YCVRC), demonstrates that CSF drainage pathways are similar between mice and humans and reports on a new imaging technique based on magnetic resonance for patients with neurological diseases.

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

The meningeal lymphatic vessels are also important for the removal of waste from the brain, being involved in the removal of interstitial fluid and soluble proteins, as well as in the drainage of CSF that provides the brain with fluid that protects against injury, a pathway for essential processes. nutrients and cellular waste removal 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 has attracted much therapeutic interest,” explains Laurent Jacob, Ph.D., first author of the study and member of the Paris research team.

“However, it was not clear 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 investigated CSF lymphatic drainage using post-mortem light sheet imaging in mice and real-time magnetic resonance imaging in humans. By combining these approaches, the authors reconstructed the entire CSF lymphatic drainage network.

3D images showed that the meningeal lymphatic vessels contact the dural venous sinuses 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.
Meningeal lymphatic vessels are potential targets for treating brain diseases. The image is attributed to the researchers.

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

Future research should explore whether these anatomical data have a causal relationship with the greater predisposition of women to develop neurological diseases such as multiple sclerosis, meningiomas or intracranial hypertension.

“Meningeal lymphatic vessels are potential targets for treating brain diseases,” Eichmann said. “Yale Laboratories are making progress in elucidating its role by imaging brain drainage by meningeal lymphatics in mice and humans.”

About this neuroscience research news

Author: Elizabeth Reitman
Font: yale
Contact: Elisabeth Reitman – Yale
Image: The image is attributed to the researchers.

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


Preserved meningeal lymphatic drainage circuits in mice and humans

Meningeal lymphatic vessels (MLVs) were identified in the dorsal and caudobasal regions of the dura mater, where they ensure the removal of waste products and immunological surveillance of brain tissues. Whether MLVs exist in the anterior part of the murine and human skull and how they connect to the glymphatic system and extracranial lymphatic vessels remained unclear.

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

We observed a preserved three-dimensional anatomy of MLV in mice and humans that aligned with the dural venous sinuses but not with nasal CSF flow, and discovered an extended anterior MLV network around the cavernous sinus, with exit routes through 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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