Neuroscientists Discover Previously Unknown Component of Brain Anatomy

A new study in the journal *Nature Aging* describes a new anatomical
structure in the brain called SLYM, an abbreviation of Subarachnoidal
LYmphatic-like Membrane, that acts as a barrier and a platform from which
immune cells can monitor the brain.

>From the complexity of neural networks to basic biological functions and
structures, the human brain only reluctantly reveals its secrets. Advances
in neuro-imaging and molecular biology have only recently enabled
scientists to study the living brain at level of detail not previously
achievable, unlocking many of its mysteries. The latest discovery,
described on January 5 in the journal *Science*, is a previously unknown
component of brain anatomy that acts as both a protective barrier and
platform from which immune cells monitor the brain for infection and
inflammation.

“The discovery of a new anatomic structure that segregates and helps
control the flow of cerebrospinal fluid (CSF) in and around the brain now
provides us much greater appreciation of the sophisticated role that CSF
plays not only in transporting and removing waste from the brain, but also
in supporting its immune defenses,” said Nedergaard.

The study focuses on the membranes that encase the brain, which create a
barrier from the rest of the body, and keep it bathed in CSF. The
traditional understanding of what is collectively called the meningeal
layer, a barrier comprised of individual layers known as the dura,
arachnoid, and pia matter.

The new layer discovered by the U.S. 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 name the SLYM, an abbreviation of *S*ubarachnoidal *LY*
mphatic-like *M*embrane. 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.

The SLYM is a type of membrane called mesothelium, which is known to line
other organs in the body, including the lungs and heart. Mesothelia
typically surround and protect organs, and harbor 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 on the systems of
barriers that protect the brain.

The new membrane is very thin and delicate, and consists of only one or a
few cells in thickness. Yet the SLYM is a tight barrier, and allows only
very small molecules to transit; it seems to separate “clean” and “dirty”
CSF. This last observation hints at the likely 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 and other neurological diseases from the
central nervous system.

The SLYM also appears important to the brain’s defenses. The central
nervous system maintains its own native population of immune cells, and the
membrane’s integrity prevents outside immune cells from entering. In
addition, the SLYM appears to host its own population of central nervous
system immune cells that use the SLYM for surveillance at the surface of
brain, allowing them to scan passing CSF for signs of infection.

Discovery of the SLYM opens the door for 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. When the membrane was ruptured during traumatic
brain injury, the resulting disruption in the flow of CSF 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 might be
triggered or worsened by abnormalities in SLYM function. They also suggest
that the delivery of drugs and gene therapeutics to the brain may be
impacted by SLYM function, which will need to be considered as new
generations of biologic therapies are being developed.

KR IRS 27123

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