A new part of the brain serves as a shield and watchdog

Researchers have discovered a previously unknown part of brain anatomy that acts both as a protective barrier and a platform from which immune cells monitor the brain for infection and inflammation.

From the complexity of neural networks to basic biological functions and structures, the human brain only reluctantly reveals its secrets.

Advances in neuroimaging and molecular biology have only recently allowed scientists to study the living brain in a level of detail never before achieved, revealing many of its mysteries.

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, professor of neuroanatomy at the University of Copenhagen.

Nedergaard and his colleagues transformed our understanding of the fundamental mechanics of the human brain and made important discoveries in the field of neuroscience, including detailing the many critical functions of previously overlooked brain cells called glia and the brain’s unique process of elimination. waste, which the laboratory has named 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 allows us to better understand the sophisticated role that CSF plays not only in transporting and removing waste from the brain, but also in supporting its immune defences,” says Nedergaard.

The study focuses on the series of membranes that wrap around the brain, creating a barrier from the rest of the body and keeping the brain bathed in CSF. The traditional understanding of what is collectively called the meningeal layer identifies the three individual layers as the dura, arachnoid, and pia matter.

The new layer discovered by the research team based in the United States and Denmark further divides the space between the arachnoid and pia layers, the subarachnoid space, into two compartments, separated by the newly described layer, than the researchers name SLYM, an abbreviation of Subarachnoidal LYmphatic-like membrane.

While much of the research in the article describes the function of SLYM in mice, it also points to its presence in the adult human brain.

SLYM is a type of membrane that lines other organs in the body, including the lungs and the heart, called the mesothelium. These membranes usually 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 posed by Møllgård, the study’s first author, whose research focuses on developmental neurobiology and the barrier systems that protect the brain.

The new membrane is very thin and delicate, composed of only a few cells thick. Yet SLYM is a tight barrier, letting only very small molecules through and also seems to separate “clean” and “dirty” CSF.

This last observation alludes to the probable role played by SLYM in the glymphatic system, which requires a controlled flow and exchange of CSF, allowing the influx of fresh CSF while flushing the toxic proteins associated with Alzheimer’s disease and other neurological diseases of the central nervous system.

This discovery will help researchers understand the mechanics of the glymphatic system more precisely.

SLYM also appears to be important for brain defenses. The central nervous system maintains its own native population of immune cells, and the integrity of the membrane prevents outside immune cells from entering. Additionally, the membrane appears to harbor its own population of central nervous system immune cells that use SLYM as an observation point near the surface of the brain from which to scan cerebrospinal fluid for signs of infection or of inflammation.

The discovery of SLYM opens the door to 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. Additionally, when the membrane ruptured during traumatic brain injury, the resulting disruption of CSF flow 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 disease could be triggered or worsened by abnormalities in SLYM function. They also suggest that the delivery of drugs and gene therapies to the brain may be affected by SLYM, which will need to be considered as new generations of biological therapies are developed.

The research appears in the journal Science. Other co-authors come from the University of Copenhagen.

The study was supported by the Lundbeck Foundation, the Novo Nordisk Foundation, the National Institute of Neurological Disorders and Stroke, the US Army Research Office, the Human Frontier Science Program, the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation, and the Simons Foundation.

Source: University of Rochester