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Scientists recently identified a new anatomical structure in the brain called SLYM, short for Subarachnoidal LYmphatic-like Membrane, which acts as a barrier and platform from which immune cells can monitor the brain.
The human brain, with its intricacies ranging from neural networks to basic biological functions and structures, remains elusive when it comes to revealing its secrets. However, recent advances in neuroimaging and molecular biology have given scientists the ability to study the living brain in unprecedented detail, uncovering many previously unknown mysteries.
A recent discovery reported in the Journal Science, describes a previously undiscovered component of brain anatomy. This new component serves both as a protective barrier and as a base from which immune cells can look for signs of infection or inflammation in the brain.
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 her colleagues have transformed our understanding of the basic mechanics of the human brain and made important discoveries in the field of neuroscience, including detailing the many critical functions of previously overlooked cells in the brain called glia and the unique process of… brain for waste disposal. which the lab called the glymphatic system.
A newly discovered membrane in the brain called SLYM is a thin but firm barrier that separates what appears to be “clean” and “dirty” CSF and houses immune cells.
“The discovery of a new anatomical structure that separates and controls the flow of cerebrospinal fluid (CSF) in and around the brain now gives us a much greater understanding of the intricate role that CSF plays, not just in the transport and removal of waste the brain but also to support the immune system,” said Nedergaard.
The study focuses on the membranes that encase the brain, which form 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 dural, arachnoid, and pial matter.
Central nervous system immune cells (shown here expressing CD45) use SLYM as a platform near the brain surface to monitor cerebrospinal fluid for signs of infection and inflammation. Photo credit: University of Rochester
The new layer, discovered by the US-Denmark-based team of researchers, further divides the space beneath the arachnoid layer, the subarachnoid space, into two compartments, separated by the newly described layer, which the researchers are calling SLYM, an acronym for Subarachnoidal LYmphatic – like membrane. While much of the research in the publication describes the function of SLYM in mice, they also report its actual presence in the adult human brain.
The SLYM is a type of membrane called the mesothelium that is known to line other organs in the body, including the lungs and heart. Mesothelia typically surround and protect organs and house immune cells. The idea that a similar membrane might exist in the central nervous system was a question first asked by Møllgård, the study’s first author. His research focuses on developmental neurobiology and on the barrier systems that protect the brain.
The new membrane is very thin and delicate, being only one or a few cells in thickness. But the SLYM is a tight barrier and only allows very small molecules to pass; it seems to separate “clean” and “dirty” CSF.
This last observation points to the likely role SLYM plays in the glymphatic system, which requires a controlled flow and exchange of CSF, allowing for the influx of fresh CSF while the associated toxic proteins are flushed out[{” attribute=””>Alzheimer’s and other neurological diseases from the central nervous system.
This discovery will help researchers more precisely 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.
The SLYM also appears important to the brain’s defenses. The central nervous system maintains its own native population of immune cells, and the membrane’s integrity prevents outside immune cells from entering. In addition, the SLYM appears to host its own population of central nervous system immune cells that use the SLYM for surveillance at the surface of brain, allowing them to scan passing CSF for signs of infection.
The Discovery of the SLYM opens the door for further study of its role in brain disease. For example, the researchers note that larger and more diverse concentrations of immune cells congregate on the membrane during inflammation and aging. When the membrane was ruptured during traumatic brain injury, the resulting disruption in the flow of CSF 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 might be triggered or worsened by abnormalities in SLYM function. They also suggest that the delivery of drugs and gene therapeutics to the brain may be impacted by SLYM function, which will need to be considered as new generations of biologic therapies are being developed.
Reference: “A mesothelium divides the subarachnoid space into functional compartments” by Kjeld Møllgård, Felix R. M. Beinlich, Peter Kusk, Leo M. Miyakoshi, Christine Delle, Virginia Plá, Natalie L. Hauglund, Tina Esmail, Martin K. Rasmussen, Ryszard S. Gomolka, Yuki Mori and Maiken Nedergaard, 5 January 2023, Science.
DOI: 10.1126/science.adc8810
The study was funded by the Lundbeck Foundation, Novo Nordisk Foundation, the National Institute of Neurological Disorders and Stroke, the U.S. Army Research Office, the Human Frontier Science Program, the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation, and the Simons Foundation.
