From the complexity of neural networks to basic biological functions and structures, the human brain has only reluctantly revealed its secrets. Only recently, advances in neuroimaging and molecular biology have allowed scientists to study living brains at previously unattainable levels of detail, unraveling many of its mysteries.The latest findings, described today in the journal sciencea previously unknown component of brain anatomy that acts as both a protective barrier and a platform for immune cells to monitor infection and inflammation in the brain.
The new research comes from the labs of Maiken Nedergaard, co-director of the Center for Translational Neuromedicine at the Universities of Rochester and Copenhagen, and Kjeld Møllgård, MD, professor of neuroanatomy at the University of Copenhagen. Nedergaard and her colleagues transformed our understanding of the fundamental mechanics of the human brain and made major discoveries in neuroscience, including the detailed description of many key functions of glial cells in the brain that were previously overlooked, and the brain’s unique waste removal process, which the laboratory named the glymphatic system.
“The discovery of a new anatomical structure that insulates and helps control the flow of cerebrospinal fluid (CSF) in and around the brain now adds to our understanding of the complex role CSF plays not only in transporting and removing waste from the brain, but also in supporting its immune defenses,” Nedergaard said.
The research focused on the membrane that wraps the brain, which forms a barrier to the rest of the body and bathes it in cerebrospinal fluid. The traditional understanding of what are collectively referred to as the meninges consists of layers called the dura mater, arachnoid mater, and pia mater.
The new layer, discovered by a team of researchers in the United States and Denmark, further divides the space below the arachnoid layer, known as the subarachnoid space, into two compartments separated by a newly described layer, which the researchers named SLYM, is the arachnoid Abbreviation for subretinal space smallsubarachnoid space Luakin ricemembrane. While most of the studies in the paper describe the function of SLYM in mice, they also report its actual presence in the adult brain.
SLYM is a membrane called the mesothelium, which is known to line other organs in the body, including the lungs and heart. Mesothelial cells normally surround and protect organs and harbor immune cells. Møllgård, the study’s first author, was the first to suggest the possibility of similar membranes in the central nervous system. His research focuses on developmental neurobiology, and the barrier system that protects the brain.
The neomembrane is very thin and fragile, consisting of only one or a few cells in thickness. However, SLYM is a tight barrier that allows only very small molecules to pass through; it appears to separate “clean” and “dirty” CSF. This last observation hints at a possible role for SLYM in the glymphatic system, which is required to control the flow and exchange of cerebrospinal fluid, allowing the inflow of fresh cerebrospinal fluid while clearing it from the central nervous system linked to Alzheimer’s and other neurological diseases Associated toxic proteins. The discovery will help researchers more precisely understand the mechanisms of the glymphatic system, which is the subject of a recent $13 million grant from the National Institutes of Health’s BRAIN program to the University of Rochester’s Center for Translational Neuromedicine.
SLYM also appears to be important for the brain’s defenses. The CNS maintains its own population of innate immune cells, and the integrity of the membrane prevents the entry of external immune cells. In addition, SLYM appears to have its own population of central nervous system immune cells that use SLYM for surveillance on 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 disorders. For example, the researchers note that during inflammation and aging, larger and more diverse immune cells accumulate on cell membranes. When membranes rupture during traumatic brain injury, disruption of CSF flow can damage the lymphatic system and allow non-CNS immune cells to enter the brain.
These and similar observations suggest that abnormal SLYM function may initiate or worsen a variety of diseases, such as multiple sclerosis, CNS infections, and Alzheimer’s. They also show that the delivery of drugs and gene therapies to the brain may be affected by SLYM function, which needs to be considered when developing next-generation biological therapies.
Additional co-authors include Felix Beinlich, Peter Kusk, Leo Miyakoshi, Christine Delle, Virginia Pla, Natalie Hauglund, Tina Esmail, Martin Rasmussen, Ryszard Gomolka and Yuki Mori from the University of Copenhagen’s Center for Translational Neuromedicine. This research was supported by the Lundbeck Foundation, Novo Nordisk Foundation, National Institute of Neurological Disorders and Stroke, U.S. Army Research Office, Human Frontier Science Program, Dr. Miriam and Sheldon G. Adelson Medical Research Foundation, and the Simons Foundation.
