Science discovers previously unknown components of the brain: the platforms on which immune cells monitor brain infections and inflammation

From the complexity of neural networks to basic biological functions and structures, we still don't
know enough about the human brain.
Until recently, advances in neuroimaging and molecular biology have enabled scientists to study the brain at previously unattainable levels of detail, unlocking many of its mysteries
.
The latest study has identified a previously unknown anatomical component of the brain that acts as both a protective barrier and a platform
for immune cells to monitor brain infections and inflammation.

The new study was led by the labs of Maiken Nedergaard, co-director of the Centre for Translational Neuromedicine at the University of Copenhagen, and Kjeld Møllgård
, professor of neuroanatomy.

Nedergaard and her colleagues have transformed our understanding of the fundamental mechanisms of the human brain and have made significant discoveries in the field of neuroscience, including detailing many of the key functions of previously overlooked brain cell glial cells, as well as the brain's unique waste removal process, which the lab has named the glymphatic system of the brain
.

"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 deeper 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 study focused on the membrane that surrounds the brain, which forms a barrier with the rest of the body and bathes it in
cerebrospinal fluid.
The traditional understanding is collectively referred to as the meningeal layer, which is a barrier
made up of individual layers called the dura, arachnoid and pia mater.

The new layer discovered by the U.
S.
and Danish 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 named Subarachnoidal LYmphatic-like Membrane (SLYM
).
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 mesothelium, which is known to line other organs of the body, including the lungs and heart
.
The mesothelium normally surrounds and protects organs and shelters immune cells
.
Kjeld Møllgård, the study's first author, first proposed the idea
that there might be a membrane-like in the central nervous system.

The new membrane is very thin and delicate, 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 seems to separate the "clean" and "dirty" cerebrospinal fluid
.
This final observation hints at the possible role SLYM may play in the lymphoid system, which needs to control the flow and exchange of CSF, allowing the inflow of fresh CSF while flushing toxic proteins associated with Alzheimer's and other neurological disorders out of the central nervous system
.
The discovery will help researchers more precisely understand the mechanisms of the lymphatic system, the subject of a recent $13 million grant from the National Institutes of Health to the University of
Rochester's Center for Translational Neuromedicine.

SLYM seems to be important
for the brain's defenses.
The central nervous system maintains its own population of immune cells, and the integrity of the membrane prevents external immune cells from entering
.
In addition, SLYM appears to have its own population of central nervous system immune cells that use SLYM to monitor the surface of the brain, allowing them to scan the passing CSF for signs of
infection.

SLYM's discovery opens the door
to further research into its role in brain diseases.
For example, the researchers noted that during inflammation and aging, larger, more diverse concentrations of immune cells accumulate on membranes
.
When the membrane ruptures in a traumatic brain injury, disruption of cerebrospinal fluid flow damages the brain's lymphoid system and allows non-central nervous system immune cells to enter the brain
.

These and similar observations suggest that a variety of diseases such as multiple sclerosis, central nervous system infections, and Alzheimer's may be triggered or worsened
by SLYM dysfunction.
They also note that the delivery of drugs and gene therapies to the brain may be influenced by SLYM function, which needs to be considered as a new generation of biological therapies
develops.