Newly discovered anatomy protects and monitors the brain
Abstract: Researchers have discovered a previously unidentified component of the brain’s anatomy that acts as both 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 is only reluctantly revealing its secrets. Advances in neuro-imaging and molecular biology have only recently enabled scientists to study the living brain at a level of detail not previously possible, unlocking many of its mysteries.
The latest discovery, described today in the journal Scienceis a previously unknown component of brain 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 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 fundamental mechanics of the human brain and made significant discoveries in the field of neuroscience, including details of many critical functions of previously overlooked cells in the brain called glia and a unique waste-removal process from the brain, which the lab calls the glymphatic system.
“The discovery of a new anatomical structure that separates and helps control the flow of cerebrospinal fluid (CSF) in and around the brain now gives us a much greater understanding of the sophisticated role that CSF plays not only in transporting and removing waste from the brain, but also in supporting its immune defenses,” Nedergaard said.
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 cerebrospinal fluid. The traditional understanding of what is collectively called the meningeal layer, a barrier consisting of individual layers known as the dura, arachnoid and pia matter.
The new layer discovered by the US-Denmark-based research team further divides the space below the arachnoid layer, the subarachnoid space, into two compartments, separated by a newly described layer, which the researchers call SLYM, short for WITHubarachnoid LYempathically similar Mmembrane. Although much of the research in the paper describes the function of SLYM 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. Mesothelioma usually 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 raised by Møllgård, the first author of the study. His research focuses on developmental neurobiology and 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. However, SLYM is a solid barrier and allows only very small molecules to pass through; it appears to separate “clean” and “dirty” cerebrospinal fluid.
This latter observation points to a likely 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.
The discovery will help researchers more precisely understand the mechanics of the glymphatic system, which was recently the subject of a $13 million grant from the National Institutes of Health BRAIN Initiative to the Center for Translational Neuromedicine at the University of Rochester.
SLYM also appears to be important for brain defense. The central nervous system maintains its own natural population of immune cells, and membrane integrity prevents the entry of external immune cells. Additionally, 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 passing cerebrospinal fluid for signs of infection.
The discovery of SLYM opens the door to further study of its role in brain diseases. For example, researchers note that higher and more diverse concentrations of immune cells gather at the membrane during inflammation and aging. When the membrane ruptured during traumatic brain injury, the resulting disruption in CSF flow damaged the glymphatic system and allowed 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 disease may be driven or exacerbated by abnormalities in SLYM function. They also suggest that delivery of drugs and gene therapeutics to the brain may be influenced by SLYM function, which will need to be considered as new generations of biologic therapies are developed.
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 Center for Translational Neuromedicine at the University of Copenhagen.
About this neuroanatomy research news
Original research: Closed access.
“The mesothelium divides the subarachnoid space into functional compartments” Kjeld Møllgård et al. Science
The mesothelium divides the subarachnoid space into functional compartments
The central nervous system is lined with meninges, classically known as dura, arachnoid and pia mater.
We show the existence of a fourth meningeal layer that divides the subarachnoid space in the mouse and human brain, called the subarachnoid lymphatic membrane (SLYM). SLYM is morpho- and immunophenotypically similar to the mesothelial membrane envelope of peripheral organs and body cavities, and envelops blood vessels and contains immune cells.
Functionally, the close apposition of SLYM to the endothelial lining of the meningeal venous sinus allows direct exchange of small solutes between the cerebrospinal fluid and venous blood, thus representing the murine equivalent of arachnoid granulations.
Functional characterization of SLYM provides fundamental insights into brain immune barriers and fluid transport.