Waste in the brain? Why the brain needs “cleaning” – and what this has to do with migraine

Waste in the brain? Why the brain needs “cleaning” – and what this has to do with migraine 

For your brain to stay healthy and work properly, it needs regular cleaning. The brain works hard around the clock, and that constant activity produces waste. If these waste products aren’t cleared away, the brain can’t do its job properly. In the rest of the body, this clean-up is handled by the lymphatic system. It picks up the waste that builds up during all the processes going on in the body and helps carry it away for disposal. The brain, however, isn’t directly connected to this system. For a long time, scientists didn’t understand how waste removal worked there. What wasn’t in doubt was that the brain would need an especially efficient system. Brains do all our thinking and have a very high metabolic rate. As a result, they produce lots of waste - and the nerve cells of the brain are highly sensitive to it.

A major breakthrough came in 2012, when Danish-American neuroscientist Maiken Nedergaard and her team described the “glymphatic” system. This system works alongside the body’s lymphatic system and helps clear waste from the brain in a reliable and effective way. (See this article describing the glymphatic system and what it does.) This trailblazing discovery drew instant interest from researchers all over the world, and the glymphatic system is now a key topic in neuroscience.  

What powers the brain’s cleaning process?

One big question researchers have been asking themselves is this: what keeps the glymphatic system moving? It turns out that the pulse of the brain’s blood vessels plays an important role. As the vessels rhythmically expand and contract, they set the fluid in the glymphatic system in motion. The spaces around the blood vessels where this fluid flows (known as perivascular spaces or PVS) widen and narrow with each pulse, effectively driving circulation and helping clear waste.

This immediately raised additional questions: what happens if this process is disturbed, and what might cause this? Clues came from dementia research. Scientists had already noted that certain waste products, known as plaques, can build up in the brain. These plaques are linked to dementia and suggest that the brain’s clean-up system doesn’t always do a perfect job.

The glymphatic system and migraine

This led researchers to wonder whether natural limitations in brain clearance might also be relevant in headache disorders and conditions such as migraine. During a migraine attack, waves of activity spread across the brain. This process is known as cortical spreading depression (CSD) (read more about it in this article). Cortical spreading depression was known to increase the risk of blood flow disorders in the brain, including strokes. Given the known impact of cortical spreading depression on blood vessels, it was logical to wonder whether it might also interfere with the delicate balance governing the glymphatic system’s brain clearance efforts.

Going with the flow – or maybe not?

A team at Harvard Medical School in Boston, Massachusetts took a closer look at cortical spreading depression and its possible association with migraine. Using advanced imaging techniques in mice, they were able to watch the perivascular spaces in real time and see how they changed during a cortical spreading depression wave. What they found was quite clear: the perivascular spaces where the “cleaning fluid” flowed became narrower, and fluid flow was significantly reduced. The sophisticated field potential techniques employed in these studies showed exactly what was happening in the brain tissue.

The scientists concluded that, during cortical spreading depression, the disrupted flow clearly prevents the glymphatic system from doing its cleaning job properly. In their animal models, the researchers noted that simulated migraine attacks disrupted normal brain activity, impairing blood flow in the affected parts of the brain and interfering with toxin and waste removal. If these findings translate to humans, the hypothesis is that frequent or prolonged migraine attacks could damage or significantly add to the burden on the brain due to buildup of metabolic waste.

Left-behind free radicals and peptides: potential troublemakers

Among all the waste products that might be left behind if the glymphatic system does a poor job of cleaning the brain, which are the most likely to cause migraine attacks? Scientists have narrowed it down to two main suspects.

First, you have the reactive oxygen species (ROS) implicated in neurodegeneration. Also known as free radicals, reactive oxygen species are produced in large amounts because the brain is so active. At the same time, nerve tissue is highly sensitive to them. If reactive oxygen species are not cleared away properly, they can build up and trigger immune cells in the brain (microglia). These cells then release substances that promote inflammation. In excess, reactive oxygen species and the substances they produce can trigger nerve cell death. This process culminates in inflammatory processes in the brain that many researchers have long suspected of triggering migraine attacks. Pro-inflammatory substances can also significantly increase pain perception and activate pain receptors (nociceptors). All of this can make a migraine worse, researchers believe.

The second suspect is a molecule called CGRP (calcitonin gene-related peptide). Researchers have had their eye on CGRP for quite some time. CGRP is a protein-like substance that normally performs regulatory functions in the body, but has recently been implicated in contributing to migraine attacks. Like reactive oxygen species, CGRP needs to be removed efficiently from brain tissue. If it isn’t, it can accumulate, especially near the meninges (the membranes surrounding the brain). This build-up is thought to be another possible trigger for migraine attacks.

What about sleep?

Getting enough proper sleep is hugely important for a healthy, functioning glymphatic system. Brain clearance works best during deep sleep, meaning that getting enough deep sleep is essential for brain health. When sleep is disturbed, various signalling and inflammatory substances can build up, many of which are known to be linked to migraine.

The problem is that headaches themselves can disrupt sleep. This can lead to a vicious cycle, where poor sleep triggers migraines, and migraines in turn can seriously affect your sleep. Many studies report that people with migraine often experience worse sleep, with a tendency for attacks to occur in the morning. This has led researchers to suspect a link between nighttime disruption of glymphatic activity and morning onset of symptoms.

That said, these studies need to be interpreted carefully. They can be difficult to reproduce, and most of them are small studies with a limited number of participants. More research will be needed to fully understand what’s going on. Even so, more and more studies are pointing in the same direction: sleep, the glymphatic system and migraine seem to be closely connected.

Sleep and migraine: what you need to know

Brain clearance during sleep is hard work for the brain. It takes both time and energy. If you don’t get enough sleep, your brain will not have the time it needs to complete its “cleaning shift”. On the other hand, sleeping too long puts more strain on the brain, without refilling its energy stores in time. Either way, the instability is a typical migraine trigger.

Anyone prone to migraine attacks should aim for a consistent sleep schedule, going to bed and getting up at similar times every day – weekends included. For people with migraine, regularity matters a lot. Good sleep hygiene also helps. For a proper night’s sleep, you need to wind down before going to bed. Avoiding screens before bed is a good idea. If switching off is difficult, you may want to try relaxation techniques before bedtime. Jacobson’s progressive muscle relaxation is a highly recommended technique for headache prevention (available in the app or here). When you get up in the morning, it’s important to eat a proper breakfast soon after waking. After a hard night’s work, your brain urgently needs new energy to get through the day.

Published: March 2026