With its complicated networks of neurons and biological structures, the brain continues to prove a difficult machine to crack. Now, thanks to advances in neuroimaging techniques and molecular biology, scientists in the United States and Denmark have discovered a new structure in the brain.
They have named it SLYM -Subarachnoid Lymph Membrane-, and they describe it as a previously unknown component of the brain’s anatomy that acts as a protective barrier and a platform for monitoring infection and inflammation. The finding, published in the journal Science, was made by scientists from the Center for Translational Neuromedicine at the University of Rochester (USA) and the University of Copenhagen (Denmark).
The brain is covered by 3 membranes, called meninges: pia mater, arachnoid mater, and dura mater. These membranes create a barrier between the brain and the rest of the body. Between the pia mater and the arachnoid mater is a space called the subarachnoid space, filled with cerebrospinal fluid, which flows in and around the brain to help cushion it and provide nutrients.
The newly discovered new structure would be a fourth membrane located in the subarachnoid space, above the pia mater, which is the innermost membrane. As the researchers explain, the function of the SLYM membrane, in addition to lining the brain, appears to be to help control the flow of cerebrospinal fluid in and out of the brain. “Our hypothesis is that SLYM can act as a barrier between the “clean” cerebrospinal fluid that enters the brain, and the ‘dirty’ fluid that comes out, dragging waste proteins with it”, Dr. Virginia Plá Requena explains to BBC Mundo, a researcher at the Center for Translational Neuromedicine at the University of Copenhagen, and one of the study’s authors. “Consequently, the deterioration of this membrane would make it difficult to cleanse the brain, affecting neuronal function”, she adds.
Indeed, the researchers believe that the SLYM finding represents the discovery of a new level of organization in the circulation of cerebrospinal fluid. And the presence of the SLYM membrane seems to confirm the sophisticated role that this fluid plays in maintaining the brain’s immune defenses and in the transport and elimination of toxic waste. Much of this toxic waste has been associated with neurodegenerative diseases such as Alzheimer’s and other disorders of the central nervous system.
“Mesothelium of the brain”
The scientists explain that SLYM is a “mesothelium,” a type of membrane found covering other organs in the body, such as the lungs and heart. These membranes work by protecting organs and storing immune cells.
The researchers suggest that SLYM is the mesothelium of the brain and works by lining the blood vessels in the cavity between the brain and the skull. And it could also act as a lubricant in this cavity. “Physiological pulsations induced by the cardiovascular system, breathing, and changes in head position constantly move the brain within the cranial cavity”, the researchers explain. “Like other mesothelia, SLYM could reduce friction between the brain and skull during such movements”, they add.
The membrane was discovered in mice, but the researchers say they were later able to see it in human brains donated for research. They assure that it could not be observed before because it disintegrates when the brain is extracted from the skull in autopsies. Plus, they say, it is too thin -just a few cells thick- and cannot be seen in living people through brain scans.
Ten years ago, the same team of neuroscientists from the Universities of Rochester and Copenhagen transformed the understanding of brain processes and mechanics when they published the discovery of the so-called glymphatic system. Then they described it as a mechanism whose function is to eliminate or clean the waste that accumulates in the brain. These products include the so-called beta-amyloid and tau proteins, which are thought to be involved in Alzheimer’s when they accumulate in excessive amounts.
Since the discovery, several teams of researchers have been carrying out studies to unravel how exactly the glymphatic system works, why it fails in certain cases, and what happens when it does. Experts believe that the discovery of the SLYM membrane could have important implications for understanding the exact functions of the glymphatic system. And it could open the door for new research to monitor this structure and watch for signs of infection or inflammation that lead to diseases of the central nervous system.
For example, the researchers suggest that because of the role that the SLYM membrane may play in cerebrospinal fluid circulation, its deterioration could make it more difficult to remove toxic waste that contributes to the plaques that lead to Alzheimer’s. And the membrane also appears to play a role in defending the brain, preventing foreign immune cells from entering the native population of brain cells, which can contribute to inflammation and the progression of cognitive decline.
More research will now be needed to understand what the implications of the existence of the SLYM membrane are. But as Dr. Virgina Plá assures, understanding how this membrane works could be key to the design of new drugs, for example drugs that can cross the blood-cerebrospinal barrier.
Also, due to its location, the membrane could be “a key element in inflammatory processes, such as those that occur in head injuries, meningitis and multiple sclerosis. Finally, knowing how this membrane changes in response to neurodegeneration or aging may be essential in interventions to maintain cognitive function”, says the researcher.
For his part, Dr. Jordi Vilaplana, a professor in the Department of Biochemistry and Physiology at the University of Barcelona and a researcher on aging and neurodegeneration, considers that the possible presence of this membrane “is very interesting.” “It would be one more element to take into account for understanding the functioning of the glymphatic system, of which there are still some questions regarding its structure and functioning”, affirms the researcher, who was not involved in this study. “However, from my point of view, the main revolution is the discovery of the glymphatic system itself, and its possible involvement, among others, with neurodegenerative diseases”, says the expert.