Brain pumps waste products away

This discovery caused quite a stir: the brain disposes of its waste products via a kind of parallel circuit next to the blood vessels. Such a separate cleaning system does not occur anywhere else in the body. However, Beatrice Bedussie, who recently obtained her doctorate from the University of Amsterdam, discovered this route is different than expected.

In 2012, Danish researcher, Maiken Nedergaard discovered that discharge via a parallel circuit mainly occurs when we are sleeping. So, the brain cleans itself. This prevents the waste products produced by the brain cells from accumulating and disrupting the functioning of the brain. Nedergaard gave this cleaning system its own name: the glymphatic system. The Danish researcher and her colleagues saw in mice that, next to the blood vessels in the brain, there is a space along which brain fluid is pumped towards the veins. The waste is immediately taken along this route. When the glymphatic system is not functioning properly, waste accumulates in the form of protein clumps. “This process could play a role in Alzheimer's disease,” says Beatrice Bedussi's co-supervisor, Dr. Erik Bakker from the Department of Biomedical Engineering and Physics. 

3D reconstruction 

Partly in view of the link with Alzheimer's disease, Bakker's group is very interested in the way in which brains dispose of their waste. “For example, we want to know what the driving forces of these fluid flows are and how high blood pressure or a stroke disrupts the cleaning system.” AMC PhD Candidate, Bedussi tried to copy Nedergaard's mouse studies, so that she could build on them. “To do this, we made a part of the mouse skull thinner, so that you can see through it with a light microscope. We used microspheres - tiny spheres that can be filled with a specific substance. We then followed these spheres along these blood vessels”. In other experiments, Bedussi injected a fluorescent substance into the brain and made a 3D reconstruction based on hundreds of microscopic samples. “This allowed us to study the glymphatic system.”

Alternative explanation

It was clearly visible through the light microscope that next to the blood vessels of the brain, there is indeed a kind of tubing through which the cerebrospinal fluid flows. However, Bedussi could not confirm that the fluid flows through the brain in the direction of the veins. On the contrary, it seems that everything flows exactly in the other direction, towards the arteries.

On the basis of the images with the light microscope, the PhD student provides an alternative explanation of the way in which the collection of the waste materials works. Bakker: “Because the arteries pulsate a little, there is movement in the space next to them. As a result, the waste products from the brain mix with the brain and spinal fluid. Compare it to a tea bag that you move back and forth in a cup of water.”

Sieve with residue

Bedussi also wanted to know which factors can disrupt the glymphatic system. She saw that the fluid flow in the brains of rats with high blood pressure is much greater than in animals with normal blood pressure. “At first sight that may seem favourable, but we think that this disrupts the normal disposal of waste. Water and salts are quickly removed, while larger molecules accumulate in many places. It is, as it were, a sieve, in which residue remains. And that residue causes damage. This is sufficient reason to further investigate the relationship between high blood pressure and dementia in the coming years”, says co-supervisor Bakker.

Source: Irene Elzakker