Newly Discovered Anatomy Shields and Monitors 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 reveals its secrets only reluctantly. Advances in neuroimaging and molecular biology have only recently enabled scientists to study the living brain at a level of detail previously unattainable, unlocking many of its mysteries.

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

The new study comes from the laboratories 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, a 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 many critical functions of previously overlooked cells in the brain called glia and the unique process of garbage disposal brain. which the lab called the glimpatic 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 provides us with a much greater appreciation of the sophisticated role that CSF plays in not only transporting and removing brain waste. but also in supporting her immune defense,” 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 meaning of what is collectively called the meningeal layer, a barrier composed of individual layers known as the dura, arachnoid, and pia.

The new layer discovered by the US- and Denmark-based 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, short for Subarachnoid LYmphatic – like a membrane. While 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 as well.

SLYM is a type of membrane called mesothelium, which is known to line other organs in the body, including the lungs and heart. The mesothelium normally surrounds and protects organs and houses immune cells.

The idea that a similar membrane might exist in the central nervous system was a question first posed by Møllgård, the first author of the study. His research focuses on developmental neurobiology and the barrier systems that protect the brain.

The new membrane is very thin and delicate and is only one or a few cells in thickness. However SLYM is a narrow barrier and allows only very small molecules to pass; appears to separate “clean” and “dirty” CSF.

The new study in Nature Aging describes a new anatomical structure in the brain called SLYM, short for Subarachnoid Lymphatic Membrane, that acts as a barrier and a platform from which immune cells can monitor the brain. Credit: University of Copenhagen

This latter observation hints at the potential role played by SLYM in the lymphatic system, which requires a controlled flow and exchange of CSF, allowing the influx of fresh CSF while clearing toxic proteins associated with Alzheimer’s and other diseases. other neurological from the central nervous system.

The 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.

SLYM also appears important for brain protection. The central nervous system maintains its native population of immune cells, and membrane integrity prevents foreign immune cells from entering. 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 passing CSF 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 greater and more diverse concentrations of immune cells accumulate in the membrane during inflammation and aging. When the membrane ruptured during traumatic brain injury, the interruption of CSF flow damaged 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 caused or exacerbated by abnormalities in SLYM function. They also suggest that the delivery of drugs and gene therapies to the brain may be affected by SLYM function, which will need to be considered as new generations of biologic therapies are developed.

Other co-authors 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.

See also

About this neuroanatomy research news

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

Original Research: Closed Access.
“A mesothelium divides the subarachnoid space into functional compartments” by Kjeld Møllgård et al. science

abstract

A mesothelium divides the subarachnoid space into functional compartments

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

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

Functionally, the close adjacency of SLYM to the endothelial layer of the meningeal venous sinus allows direct exchange of small solutes between 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.