Humans have a fourth meninges in our brains, shows study

(K. Møllgård et al. / Science, 2023 https://bit.ly/3GH50nA)

Neuroscientists from the University of Rochester Medical Center and the University of Copenhagen have discovered the fourth shell of the brain.

The thin membrane is located between the middle and inner meningeal membranes, is impermeable to large molecules and actively participates in inflammatory processes.

The neurons of the brain are not directly adjacent to the bones of the skull - they are covered with meningeal membranes, which differ in structure and function.

Classically, three layers are distinguished, and the outermost (the dura mater) is responsible for the mechanical protection and stabilization of the brain.

The middle, arachnoid membrane also protects against damage, and also forms thin villous outgrowths to absorb cerebrospinal fluid into the blood.

Finally, the thinnest, the soft shell that fits snugly to the brain and carries blood vessels.

Cerebrospinal fluid circulates between the membranes of the brain, it washes the brain and carries away metabolic products.

In 2012, scientists described the glymphatic system, the outflow of cerebrospinal fluid through the lymphatic vessels of the meninges.

This helped to better understand the metabolism and immunity of the central nervous system.

Nevertheless, there are still many questions about how substances are transported between the brain and the rest of the body.

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A NEW MEMBRANE
Now the Rochester team, led by Maiken Nedergaard is closer to understanding the complex structure of the meninges.

The neuroscientists studied the flow of cerebrospinal fluid and found a thin layer of cells that expressed the Prox1-EGFP gene, a marker of the lymphatic system.

The cell membrane was called the lymphatic-like subarachnoid membrane or “SLYM” (subarachnoid lymphatic-like membrane)

The membrane was located between the soft and arachnoid membranes and divided the subarachnoid space into two floors.

And although the bulk of research has traditionally been done in mice, scientists have confirmed the presence of the same membrane in humans.

To check whether the membrane creates an obstacle to the flow of substances, the scientists conducted an experiment.

(K. Møllgård et al. / Science, 2023 https://bit.ly/3XhFah7)

They took two substances with a molecular size of one micrometer, the blue substance was introduced into the space above the membrane, and the red one - under it.

So SLYM proved its barrier properties: the molecules could not pass through the membrane from either side.

However, there are many cytokines, growth factors and other substances in the body that are less than one micrometer in size.

In an experiment with mice, scientists used tetramethylrhodamine with a molecular size of three kilodaltons, in some mice it crossed the membrane, while in others it did not.

Thus, SLYM was found to be permeable to substances less than or equal to three kilodaltons.

On immunohistochemistry, SLYM stained positively for a unique set of markers, distinguishing it from other meninges and lymphatics.

This allowed the authors of the study to isolate SLYM as a separate fourth meningeal membrane.

In addition, SLYM was positive for podoplanin, making it similar to mesothelium, the tissue that lines the abdominal, pericardial, and other body cavities.

Scientists suggest that SLYM, like other mesothelial membranes, protects against friction that occurs between the brain and skull during head movements.

SLYM was also actively involved in the immune processes of the brain - it contained immune cells, and during inflammation, their number and diversity increased markedly.

Moreover, with mechanical damage to the brain, SLYM was torn, and immune cells rushed straight to the brain.

Scientists believe this may explain the long-term inflammation in the brain after injuries.

The discovery of an additional membrane will help to better understand the diseases of the nervous system, and SLYM will be studied further.

But it is already clear that the membrane is strongly involved in the immunity of the brain, and the permeability is a significant regulator of the transport of many proteins

These might include the infamous beta-amylamide and tau protein, associated with Alzheimer's disease.

Sources:

• Science: https://www.science.org/doi/10.1126/science.adc8810
• URM: https://www.urmc.rochester.edu/news/story/newly-discovered-anatomy-shields-and-monitors-brain
• New Scientist: https://www.newscientist.com/article/2353622-weve-just-discovered-a-new-part-of-the-brains-waste-disposal-system/

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