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MS immune cells may enter the brain via a newly discovered ‘sewer system’

In inflammatory neurological conditions like multiple sclerosis (MS), inflammatory immune cells can enter the brain through arachnoid cuff exit points (ACE), recently discovered structures that normally appear to serve as a type of immune system. sewer in the brain, helping to remove waste. .

Determining exactly how immune cells and inflammatory signaling molecules move across ACE points – leading to inflammation in the brain – could lead to new therapeutic strategies for MS and other disorders, researchers said in a study entitled “Identification of direct connections between the dura mater and the brain”, which was published in Nature.

The brain is surrounded by a series of membranes called the meninges. These membranes have long been thought to insulate the brain from the rest of the body, protecting it from potentially harmful substances.

However, this new study shows that there are actually spaces between the middle, or arachnoid, layer of the meninges and its outer layers, called the dura, which researchers described as the brain’s strong protective covering. The team discovered that some immune cells are able to move across these ACE points – and as such, they could provide a sort of gateway for immune cells to pass into the brain.

“The immune system uses molecules to communicate that pass from the brain to the dura mater,” said Jonathan Kipnis, PhD, professor at Washington University in St. Louis and author of the study, in a press release . “This crossover must be closely regulated, otherwise adverse effects on brain function may occur.”

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Waste fluids escape from the brain “much like sewage leaves our homes”

Gaps between layers of the meninges occur where blood vessels pass through them, the researchers noted. Instead of forming a tight seal around these vessels, the arachnoid layer instead forms a looser ring that is more akin to a cuff – leading the team to name these structures arachnoid cuff exit points, or points. ACE for short.

Through a series of imaging tests in mice and human volunteers, researchers showed that fluids, molecules, and even some immune cells are able to move across ACE points. Based on how these substances circulate under normal conditions, researchers believe it likely serves to clear waste from the brain.

Daniel Reich, MD, PhD, of the National Institute of Neurological Disorders and Stroke (NINDS) and co-author of the study, compares this function of ACE points to the way pipes carry sewage out of water. ‘a house.

In this study, we asked the question of what happens once the “drain pipes” leave the “house” – in this case, the brain – and connect to the city sewer system at inside the body.

“Waste fluids move from the brain to the body, much like sewage leaves our homes,” Reich said.

“In this study, we asked the question of what happens once the ‘drain pipes’ leave the ‘house’ – in this case, the brain – and connect to the city’s sewer system inside the body,” Reich said.

If ACE points do indeed serve the brain to eliminate waste, then they could have important implications in many neurological disorders, such as Alzheimer’s disease, characterized by abnormal protein clumps in the brain.

“If your sink is clogged, you can remove the water from the sink or repair the faucet, but ultimately you have to repair the drain,” Reich said.

“In the brain, blockages at ACE points can prevent waste from coming out. If we can find a way to clear these plugs, we may be able to protect the brain,” he said.

This work is a collaboration between scientists at the University of Washington and NINDS, part of the National Institutes of Health. It was funded by the NINDS Intramural Research Program, the National Institute on Aging, and the Cure Alzheimer’s Fund BEE Consortium.

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An illustration of white and red blood cells, photographed up close.

More immune cells observed at ACE points in the brain in an MS mouse model

As part of the study, the researchers also looked at what happens to ACE points in mice with experimental autoimmune encephalomyelitis (EAE) – a laboratory-induced inflammatory disease that is commonly used to model MS.

The results showed that, under inflammatory conditions, there was a marked increase in the number of immune cells clustered around ACE spots. The ACE dots cells themselves also showed changes that appeared to make it easier for immune cells to pass through.

Based on these results, the researchers hypothesized that ACE dots may provide an important entry point for inflammatory immune cells in disorders like MS.

If true, this implies that preventing movement via ACE points could be a therapeutic strategy in neuroinflammatory disorders. The researchers stressed, however, that much more work is needed to understand the exact biological mechanisms involved.

“Unraveling the processes that govern the movement of cells and molecules across ACE points could provide therapeutic targets in neurological diseases,” the team wrote.

The scientists said the results of this study provide “a conceptual framework to underpindiscover how the arachnoid barrier allows both separation and communicationcommunication between the meningeal layers.

“We describe a new aspect of ffunctional anatomy… and propose that ACE points are essential for… waste elimination and for neuroimcommon communication in physiology and pathology (disease development),” they concluded.

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