Research Shows Brain’s “Drain Pipes” Connect to Immune System

Researchers from Washington University in St. Louis and scientists from the National Institute of Neurological Disorders and Stroke (NINDS), a division of the National Institute of Health (NIH), have found a direct link between the dura mater, the brain’s hard protective covering, and the waste drainage system of the brain. These connections might let waste products exit the brain while exposing it to immune cells and other dura-derived signals. This contradicts the traditional understanding, which holds that the brain is shielded from harmful substances and pollutants present in the environment by a network of walls separating it from its surroundings.  

According to Daniel S. Reich, M.D., Ph.D. of NINDS, “waste fluid moves from the brain into the body much like how sewage leaves our homes.” “What happens once the ‘drain pipes’ leave the ‘house,’ in this case the brain, and connect up with the city sewer system within the body, is the question we asked in this study.” Reich’s group collaborated with the lab of Washington University in St. Louis professor Jonathan Kipnis, Ph.D.  

Reich’s lab observed the relationship between the human body’s lymphatic system and brain using high-resolution magnetic resonance imaging (MRI). In the meantime, Kipnis’s group was independently studying these systems in mice using live-cell and other tiny brain imaging techniques.  

The researchers employed magnetic resonance imaging (MRI) to scan the brains of a group of healthy volunteers who had been injected with gadobutrol, a magnetic dye used to visualize blood vessel damage and disturbances in the blood brain barrier. The MRI scans made visible the large veins that are known to move blood away from the brain through the arachnoid barrier. A ring of dye that gradually expanded around those massive veins as the scan went on suggested that fluid could be able to get through the area where those enormous veins cross past the arachnoid barrier and enter the dura.  

Similar findings in mice were being observed by Kipnis’s lab. His team gave mice injections of compounds that emit light. Similar to the MRI tests, it was observed that fluid containing these light-emitting molecules could flow through the blood vessel-passing arachnoid barrier.  
The laboratories collectively discovered a “cuff” of cells that encircles blood vessels as they move through the arachnoid region. These regions, known as arachnoid cuff exit (ACE) sites, seem to function as conduits for fluid, chemicals, and even some cells to go from the dura into the brain and vice versa without allowing the two fluids to completely mix. Disease-causing proteins may accumulate as a result of poor waste clearance in some conditions, such in Alzheimer’s disease. Kipnis continued the sewage analogy and described how there might be a link to ACE points:  
“In the end, you need to fix the drain if your sink is clogged. You can clear the water or adjust the faucet,” he advised. Waste may not be able to exit the brain if there are blockages at ACE sites. It could be able to safeguard the brain if we can figure out how to clear these obstructions.  

ACE points suggest, among other things, that the immune system can respond to changes in the brain by being exposed to these regions. Immune cells were seen surrounding ACE points and even between the blood vessel wall and the cuff cells in mice that Dr. Kipnis’s lab had been used to produce a condition where the immune system assaults the myelin in the brain and spinal cord. Over time, this resulted in a collapse of the actual ACE point. The degree of infection was decreased when immune cells’ capacity to engage with ACE sites directly was inhibited.  
According to Kipnis, “molecules that cross from the brain into the dura mater are used by the immune system to communicate.” “Tight regulation of this crossing is necessary to prevent negative effects on brain function.”  
Reich and his colleagues also noticed an intriguing relationship between the age of the individuals and the ACE sites’ leakiness. More dye spilled into the surrounding fluid and the area around the blood vessels in the elderly participants.  
According to Reich, “this might indicate a gradual breakdown of the ACE points over the course of aging, and this could be consequential in that the immune system and brain can now interact in ways that they shouldn’t.”  
The relationship between aging and the breaking down of an immune system-brain barrier aligns with observations made in aging animals and autoimmune diseases such as multiple sclerosis. More research is required to validate this connection, but it may help explain why our age-related increase in the risk of neurodegenerative disorders is related to this newly discovered link between the brain and immune system. 

News Reference  

National Institute of Health, https://www.nih.gov/news-events/news-releases/new-direct-links-discovered-between-brain-its-surrounding-environment.