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Newly discovered anatomy protects and monitors the brain

Summary: Researchers have discovered a previously unidentified component of the brain’s anatomy that acts as a protective barrier and a platform by 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 only reluctantly reveals its secrets. Advances in neuroimaging and molecular biology have only recently allowed scientists to study the living brain at a previously unattainable level of detail, unlocking many of its mysteries.

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

The new study comes from the labs 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 his colleagues have transformed our understanding of the fundamental mechanics of the human brain and made significant discoveries in the field of neuroscience, including detailing the many critical functions of previously neglected cells in the brain called glia and the brain’s unique process of waste removal, 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 provides us with a much greater appreciation of the sophisticated role that CSF plays not only in transporting and removing waste products. of the brain, but also in supporting their immune defenses,” said Nedergaard.

The study 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 made up of individual layers known as the dura mater, arachnoid mater and pia materia.

The new layer discovered by the US and Danish 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, an abbreviation for subarachnoid ALphatic type 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 line other organs in the body, including the lungs and heart. Mesothelia normally surrounds and protects organs and harbors immune cells.

The idea that a similar membrane might exist in the central nervous system was a question first posed by Møllgård, the study’s first author. His research focuses on developmental neurobiology 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 thick. However, SLYM is a rigid barrier and allows only very small molecules to pass through; seems to separate “clean” from “dirty” CSF.

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

This last observation suggests the likely role played by SLYM in the glymphatic system, which requires a controlled flow and exchange of CSF, allowing the influx of fresh CSF while releasing the toxic proteins associated with Alzheimer’s disease and other neurological diseases of the central nervous system.

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

SLYM also appears to be important for the brain’s defenses. The central nervous system maintains its own native population of immune cells, and membrane integrity prevents outside immune cells from entering. Furthermore, SLYM appears to host its own population of central nervous system immune cells that use SLYM for surveillance on the surface of the brain, allowing them to scan the CSF for signs of infection.

The discovery of SLYM opens the door to further study of its role in brain disease. For example, researchers observe that larger and more diverse concentrations of immune cells gather at the membrane during inflammation and aging. When the membrane was ruptured during a traumatic brain injury, the resulting interruption in CSF flow impaired the glymphatic system and allowed non-central nervous system immune cells 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 triggered or exacerbated by abnormalities in SLYM function. They also suggest that drug and gene therapy delivery to the brain may be affected by SLYM function, which will need to be considered as new generations of biological therapies are being developed.

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

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About this neuroanatomy research news

Author: Press office
Source: University of Rochester
Contact: Press Office – University of Rochester
Image: The image is credited to the University of Copenhagen

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


Summary

A mesothelium divides the subarachnoid space into functional compartments

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

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

Functionally, the close apposition of SLYM with the endothelial lining of the meningeal venous sinus allows direct exchange of small solutes between cerebrospinal fluid and venous blood, thus representing the mouse equivalent of arachnoid granulations.

The functional characterization of SLYM provides fundamental information about brain immune barriers and fluid transport.