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Newly discovered anatomical brain shields and monitors

Newly discovered anatomical brain shields and monitors

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Summary: Researchers have discovered a previously unidentified component of the brain’s anatomy that acts as both a protective barrier and a platform through which immune cells monitor the brain for signs of inflammation and infection.

source: University of Rochester

From the complexity of neural networks to basic biological functions and structures, the human brain is reluctant to reveal its secrets. Advances in neuroimaging and molecular biology have only recently allowed scientists to study the living brain at a level of detail not previously achievable, unlocking many of its mysteries.

The latest discovery, described today in the journal Scienceis a previously unknown component of the brain’s anatomy that acts as both a protective barrier and a platform from which immune cells monitor the brain for infection and inflammation.

The new study comes from the laboratories of Maiken Nedergaard, co-director of the Center for Translational Neuromedicine at the University of Rochester and the University of Copenhagen, and Kjeld Møllgård, MD, professor of neuroanatomy at the University of Copenhagen. Nedergaard and her colleagues have transformed our understanding of the fundamental mechanics of the human brain and made significant discoveries in the field of neuroscience, including detailing many critical functions of previously overlooked cells in the brain called glia and the brain’s unique waste removal process, which the lab called the glymphatic system.

“The discovery of a new anatomical structure that secretes and helps control the flow of cerebrospinal fluid (CSF) in and around the brain now gives us a much greater appreciation of the complex role that CSF plays in not only transporting and removing waste from the brain, but also to support its immune defenses,” Nedergaard said.

The research focuses on the membranes that surround the brain, which create a barrier from the rest of the body and keep it bathed in CSF. The traditional understanding of what is collectively called the meningeal layer, a barrier consisting of distinct layers known as the dura, arachnoid, and pia matter.

The new layer, discovered by the US- and Denmark-based research team, further divides the space below the arachnoid layer, the subarachnoid space, into two compartments separated by the newly described layer, which the researchers call SLYM, short for Subarachnoid LYmphatic Membrane. While much of the research in the paper describes SLYM’s function in mice, they also report its actual presence in the adult human brain.

SLYM is a type of membrane called mesothelium, which is known to cover other organs in the body, including the lungs and heart. Mesothelium normally surrounds and protects organs and contains immune cells.

The idea that such a membrane might exist in the central nervous system was a question first raised by Møllgård, the first author of the study. His research focuses on the neurobiology of development and the barrier systems that protect the brain.

The new membrane is very thin and delicate and consists of only one or a few cells in thickness. Yet SLYM is a tight barrier and allows only very small molecules to pass; appears to separate “clean” and “dirty” CSF.

A new study in Nature Aging describes a new anatomical structure in the brain called SLYM, short for Subaracnoidal LYmphatic-like Membrane, which acts as a barrier and platform from which immune cells can monitor the brain. Credit: University of Copenhagen

This latter observation hints at a possible role for SLYM in the glymphatic system, which requires controlled CSF flow and exchange, allowing the influx of fresh CSF while flushing toxic proteins associated with Alzheimer’s disease and other neurological diseases from the central nervous system.

This finding will help researchers better understand the mechanics of the glymphatic system, which was the subject of a recent $13 million grant from the National Institutes of Health’s BRAIN Initiative to the Center for Translational Neuromedicine at the University of Rochester.

SLYM also appears to be important for brain protection. The central nervous system maintains its own natural population of immune cells, and membrane integrity prevents the entry of outside immune cells. In addition, SLYM appears to host its own population of central nervous system immune cells that use SLYM to monitor the surface of the brain, allowing them to scan passing CSF for signs of infection.

The discovery of SLYM opens the door to further research into its role in brain diseases. For example, researchers note that greater and more diverse concentrations of immune cells gather on the membrane during inflammation and aging. When the membrane is ruptured during traumatic brain injury, the resulting interruption of CSF flow damages the glymphatic system and allows immune cells from outside the central nervous system to enter the brain.

These and similar observations suggest that diseases as diverse as multiple sclerosis, central nervous system infections, and Alzheimer’s may be caused or exacerbated by abnormalities in SLYM function. They also suggest that the delivery of drugs and gene therapeutics to the brain may be affected by SLYM function, which will need to be taken into account as new generations of biologic therapies are developed.

Additional co-authors include Felix Beinlich, Peter Kusk, Leo Miyakoshi, Christine Dele, Virginia Pla, Nathalie Hauglund, Tina Esmail, Martin Rasmussen, Ryszard Gomolka, and Yuki Mori with the Center for Translational Neuromedicine at the University of Copenhagen.

See also

Newly discovered anatomical brain shields and monitors

About this neuroanatomy research news

Author: Press office
source: University of Rochester
Contact: Press Office – University of Rochester
Image: Image attributed to the University of Copenhagen

Original Research: Closed access.
The mesothelium divides the subarachnoid space into functional compartments” by Kjeld Møllgård et al. Science


Summary

The mesothelium divides the subarachnoid space into functional compartments

The central nervous system is covered by meninges, classically known as the dura, arachnoid, and pia mater.

We show the existence of a fourth meningeal layer that separates the subarachnoid space in the mouse and human brain, called the subarachnoid lymphoid membrane (SLYM). SLYM is morpho- and immunophenotypically similar to the mesothelial membrane lining of peripheral organs and body cavities and encloses blood vessels and contains immune cells.

Functionally, the tight adherence of SLYM to the endothelial lining of the meningeal venous sinus allows direct exchange of small solutes between CSF and venous blood, thus representing the murine equivalent of arachnoid granulations.

Functional characterization of SLYM provides fundamental insight into brain immune barriers and fluid transport.


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