Two new grants, totalling more than $4.5 million, are going to the lab of University of Rochester Medical Center scientist Maiken Nedergaard, M.D., D.M.Sc. to study a somewhat newly discovered system that keeps the brain clean. The new grants include $3.8 million from the National Institute of Neurological Disorders and Stroke (NINDS) and $769,000 from the Department of Defense.

The system that cleans out waste from the brain has been dubbed “the glymphatic system.” It pays a role in many neurological diseases, such as Alzheimer’s, amyotrophic lateral sclerosis, Huntington’s. It is named after the glial cells, which play an important role in the process, and its similarity to the lymphatic system, which cleans out other organs just not the brain.

After the glymphatic system was discovered, the findings were published in Science Translational Medicine in August 2012. Scientists have known that cerebrospinal fluid is part of the system that cleans out the brain. They found that the glymphatic system is like a layer of piping that surrounds the brain’s existing blood vessels. The glial cells called astrocytes form a channel around the outside of veins and arteries inside the brain.

The end feet of the star-shaped glial cells called astrocytes are filled with aquaporins that move cerebrospinal fluid through the brain. The cerebrospinal fluid is pumped into the brain along channels that surround arteries. Then the fluid washes through the brain tissue before collection in channels around veins. Finally, it drains from the brain.

In earlier research, the team injected amyloid beta into the brains of mice. This protein can accumulate and clump up in Alzheimer’s disease. When the researchers compared mice with a normal glymphatic system to mice with a disabled one, they found that the normal mice were able to clear the protein from the brain rapidly. The amyloid removal was diminished in brains with a disabled glymphatic system. So the brains that have a problem with the glymphatic system have the protein build up and build up until it forms plaque that clogs up the brain.

The team has also shown that the glymphatic system works primarily when we sleep, and is disrupted after traumatic brain injury in prior research.

The future research will study a couple of different topics. The NINDS grant will be used to study the incidence of “mini-strokes” in the brain. As mini-strokes accumulate over time, the result can be dementia. Nedergaard hypothesizes that the glymphatic system plays a role in these mini-strokes. Specifically, the glymphatic system isn’t working properly, which causes buildup of cerebrospinal fluid, triggering inflammation and disrupting blood flow.

The Department of Defense grant is meant to determine what happens when the glymphatic system is disrupted, like what happens after a traumatic brain injury. Amyloid beta and tau, which are normally cleared, can build up and cause problems cognitively and behaviorally. The research is geared toward service men who experience cognitive problems after TBI. The goal of the research is to develop a test to determine glymphatic system impairment and to identify treatments that could help repair the system.

Gordon Johnson

Attorney Gordon Johnson is one of the nations leading brain injury advocates. He is Past-Chair of the TBILG, a national group of more than 150 brain injury advocates. He has spoken at numerous brain injury seminars and is the author of some of the most read brain injury web pages on the internet.

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