The central nervous system is lined with meninges, classically known as dura, arachnoid, and pia mater. A new study from the University of Rochester Medical Center demonstrates the existence of a fourth meningeal layer that divides the subarachnoid space in the mouse and human brain into compartments, which the researchers call the SLYM, short for Subarachnoidal LYmphatic-like membrane.

This previously unknown part of brain anatomy acts as a protective barrier and platform from which immune cells monitor the brain for infection and inflammation. The study has transformed our understanding of the fundamental mechanics of the human brain and provided important findings in the field of neuroscience, including detailing the many critical functions of previously overlooked cells in the brain called glia and the unique the brain’s process of waste removal, which the lab called the glymphatic system.

Nedergaard said, “The discovery of a novel anatomical structure that separates and helps control the flow of cerebrospinal fluid (CSF) in and around the brain now gives us a much greater appreciation for the advanced role CSF plays, not just in transporting and removing waste products from the brain, but also in supporting the defense of the immune system.”

The SLYM is a mesothelium-type membrane, which is also known to line the lungs and heart, among other human organs. Immune cells are often housed in and around mesothelium, which also protects organs. Møllgård, the study’s first author, raised the possibility that a similar membrane might exist in the central nervous system. His work focuses on the systems of barriers that protect the brain and developmental neurobiology.

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

This latter finding suggests the potential function of SLYM in the glymphatic system, which requires controlled flow and exchange of CSF to allow the entry of new CSF while keeping the harmful proteins associated with Alzheimer’s disease and other neurological diseases out of the central nervous system are flushed out.

Scientists noted, “This discovery 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.”

Maiken Nedergaard, co-director of the Center for Translational Neuromedicine at the University of Rochester, said: “The discovery of the SLYM opens the door for further research into its role in brain diseases. For example, the researchers note that during inflammation and aging, greater and more diverse concentrations of immune cells converge on the membrane. When the membrane ruptured during traumatic brain injury, the resulting disruption in the flow of CSF compromised 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 disease may be caused or exacerbated by abnormalities in SLYM function. The observations also suggest that the delivery of drugs and gene therapeutics to the brain may be affected by SLYM function, which should be considered in the development of new generations of biologic therapies.”

Magazine reference:

  1. Kjeld Møllgård, Felix RM Beinlich, Peter Kusk, Leo M. Miyakoshi, Christine Delle, Virginia Plá, Natalie L. Hauglund, Tina Esmail, Martin K. Rasmussen, Ryszard S. Gomolka, Yuki Mori, Maiken Nedergaard. A mesothelium divides the subarachnoid space into functional compartments. Science, 2023; 379 (6627): 84 DOI: 10.1126/science.adc8810