A clear solution for cleaning your brain

May 14th, 2024

Written by: Joe Stucynski

If you have ever woken up from a good night’s sleep and felt particularly alert, refreshed, and clear-headed, you might not have realized that during the night your brain cleaned itself! Since the brain consumes a huge amount of your body’s energy, it generates a lot of waste. But unlike the rest of your body, which deposits waste products in your bloodstream to be filtered out by your kidneys, the brain, trapped in your skull, must do things differently. Instead, all of those waste products float in cerebrospinal fluid or CSF, a clear liquid similar to blood plasma that flows in and around the brain. CSF does many things for your brain including acting as a cushion and delivering hormones and nutrients. But exactly how CSF cleans the brain was somewhat of a mystery. Fortunately, recent research studies have filled in key pieces of the puzzle. It turns out that the large brain waves you experience while sleeping help push CSF and the garbage it carries, just like trash floating on the surface of the ocean!

Brain Baths – what we know

The importance of understanding how the brain deals with waste has grown tremendously. Incurable neurodegenerative disorders like Alzheimer’s and dementia are characterized by buildup of unwanted waste products and severe sleep problems.¹ As the prevalence of these disorders grows, it’s important to understand whether being unable to clean the brain at night can be a cause or a symptom of these diseases (or both!).

To that end, almost 10 years ago researchers discovered a network of plumbing in the brain they dubbed the glymphatic system.² This system acts like the sewers of a city, providing an important network of disposal pipes lining the arteries and veins throughout the brain that the cerebrospinal fluid can drain waste into. However, since this plumbing network only lines arteries and major veins, scientists didn’t understand how the brain might push waste from interior, hard to reach areas of the brain, to outer arteries. In essence, a city needs workers to wash the alleys between densely packed buildings in order to push waste to the major sewer drains.

One key clue to how the brain might do this is that when you are asleep or under some types of anesthesia, neurons shrink in size, causing the space between cells to become larger. This allows CSF and waste products to move more freely around the neurons.² This would be like if during the nighttime, all of the city buildings suddenly shrank, causing all of the streets to get wider. In this case, it would be much easier to get in there and clean the streets. And this happens across the entire brain! But still the question remains… who does the sweeping?

To answer this question, a group of neuroscientists looked at fluid movement in the brain using a method called functional Magnetic Resonance Imaging (fMRI). They found that when a brain area becomes very active and needs more oxygen, the blood volume around those active neurons increases.³ Hence, when the neurons quiet down, it causes the blood flow to recede. Because the skull has a fixed volume, when the arteries shrink again new cerebrospinal fluid is sucked in and fills the space, washing away the old waste filled CSF. So it seems that at least on a large scale, the brain itself washes itself during sleep. But what about on the small scale? What exactly are neurons doing that cause these rushes of CSF, and can they actually do any of the cleaning themselves?

Motion of the ocean

You can think of the brain when it’s awake like the ocean on a clear sunny day. There may be currents, but the surface of the water is flat because waves are moving in every direction and cancelling each other out. So too, the brain has lots of desynchronized activity. However, the sleeping brain is like the ocean on a stormy and windy day, with lots of large, slow and synchronized electrical waves. These waves carry energy and can push things. Just ask any fisherman.

The authors of a recent study⁴ reasoned that large, slow electrical waves in the brain when you are asleep can actually drag along charged molecules in the space surrounding neurons, thereby creating waves in the fluid as well. To test this, while mice were sleeping, the neuroscientists silenced the hippocampus, an area of the brain involved in learning and memory. They then injected a dye into the CSF of the mice. If it is true that large brain waves during sleep can create waves in the CSF as well, they expected to see lots of dye in every area of the brain except for the silent hippocampus. And this is what they found – very little of the dye was able to penetrate into the hippocampus compared to the rest of the sleeping brain! In other words, the CSF around those neurons was completely stagnant and any waste would not be cleared.

They then tried the reverse experiment to directly test the idea that lack of large brain waves prevents waste removal. They reasoned that if they silenced neurons in the hippocampus and no brain waves occur there, it would prevent waste filled CSF from leaving. They again injected a dye into the sleeping brains, but this time they waited for it to spread all over the brain. Only after the dye spread everywhere did they silence the hippocampus. They then waited for the mice to continue sleeping and observed that, while the dye levels in the rest of the sleeping brain decreased over time, the hippocampus was still filled with dye! This confirmed that not having large electrical brain waves that occur during sleep prevented waves in the CSF from forming and cleaning the brain!

While there’s still a lot to be learned about how the brain cleans itself, and there’s still some debate among scientists over how this exactly happens and the role of sleep,⁵ we now have a much better picture. In the future, it might even be possible to help the brain get rid of its garbage in order to help people with debilitating diseases!

References

1. Cedernaes, J., Osorio, R.S., Varga, A.W., Kam, K., Schioch H.B., Benedict, C. Candidate mechanisms underlying the association between sleep-wake disruptions and Alzheimer’s disease. Sleep Medicine Reviews, 2017.
2. Xie, L., Kang, H., Xu, Q., Chen, M., Liao, Y., Thiyagarajan, M., O’Donnell, J., Chistensen, D.J., Nicholson, C., Iliff, J., Takano, T., Deane, R., Nedergaard, M. Sleep drives metabolite clearance from the adult brain. Science, 2013.
3. Fultz, N., Bonmassar, G., Setsompop, K., Stickgold, R., Rosen, B.R., Polimeni, J.R., Lewis, L.D. Coupled electrophysiological, hemodynamic, and cerebrospinal fluid oscillations in human sleep. Science, 2019.
4. Jiang-Xie, L., Drieu, A., Bhasiin, K., Quintero, D., Smirnov, I., Kipnis, J. Neuronal dynamics direct cerebrospinal fluid perfusion and brain clearance. Nature, 2024.
5. Miao, A., Luo, T., Hsieh, B., Edge, C.J., Gridley, M., Wong, R.T.C., Constandinou, T.G., Wisden, W., Franks, N.P. Brain clearance is reduced during sleep and anesthesia. Nature Neuroscience, 2024.

Cover photo by upklyak on Freepik.com