"Brain washing": How nightly brain cleaning prevents headaches

Our bodies are engaged in countless processes around the clock. Most of these happen without us consciously initiating them, and many go completely unnoticed. We breathe in and out all day long without thinking about it, digest food, and pump blood through our veins. All this is work that our bodies do for us. A lot of these tasks generate waste products or residues from metabolic processes. To prevent these byproducts from becoming a burden on our system, they need to be carried away for disposal.

The lymphatic system: high performance behind the scenes

This cleaning task is handled by our lymphatic system, working continuously and unnoticed. It consists of a network of fine-walled vessels that transport a yellowish-white interstitial fluid, known as "lymph," into the venous system, up to two liters daily. The lymph carries away dead cells, proteins, foreign substances, bacteria, fats and metabolic end products, eventually expelling them from the body. The lymphatic system extends throughout almost the entire body, but, interestingly, ends just outside the brain, at the meninges.

How does our brain clean itself?

The absence of lymphatic vessels in the brain has puzzled researchers for generations. The hypothesis that the brain must have some form of waste disposal mechanism was repeatedly put forward. The brain is an organ with high metabolic activity, producing a significant amount of waste, and nerve cells are especially sensitive to these substances.  Until ten years ago, there were no indications that the brain had its own cleaning system comparable to the lymphatic system. It was assumed that the waste and toxin disposal processes were largely managed by the cells themselves.

This view changed fundamentally in 2012. A research group led by Danish scientist Maiken Nedergaard discovered a physiological mechanism in the brain’s glial cells, which they named the "glymphatic system" (a portmanteau of "glia" and "lymphatic system"). They were the first to describe this functional unit.

A sensational discovery: the glymphatic system

The network of channels in this system resembles a "pipe-in-pipe" setup. The inner pipe comprises our arterial blood vessels that permeate the brain. The outer layer, called the "perivascular space" because it wraps around the vessels like a second skin, is formed by specialized nerve cells known as "astrocytes" and their extensions. A mixture of brain fluid (cerebrospinal fluid, CSF) and between-cell fluid (interstitial fluid, ISF) flows in this outer pipe. From there, it enters the brain tissue, picking up both dissolved and undissolved substances. The flow is driven by the waves of movement that travel through the walls of our arteries with each heartbeat. Once the fluid reaches the capillary veins (the "venules"), it transports waste to larger veins and releases its load into the body's lymphatic system. At this point, the brain clearance flow merges with the lymphatic system of the rest of the body. The waste is eventually eliminated through the liver and kidneys.

This discovery provides the lymphatic system with a cleaning apparatus that is just as effective as the lymphatic system, and its quantitative performance is impressive too: According to recent expert estimates, the brain produces about seven grams of waste per day—amounting to two and a half kilograms per year, almost double the brain's mass. In most cases, the neural waste disposal system handles these quantities with ease. But what happens when this process is disrupted, not effective enough or temporarily stops working?

Cleaning only happens at night

Waste disposal in the body occurs at night, making deep sleep essential for the nervous system's proper functioning. According to current research, poor sleep could contribute to a range of neurological disorders. Although findings from animal studies cannot be directly applied to humans, it is interesting to note that sleep deprivation in animals leads to a greater accumulation of harmful protein particles.

The glymphatic system and headaches

There is a close relationship between sleep and headaches. A survey by a research group in Madrid found that about half of people with tension headaches or migraines also suffer from severe sleep disturbances. The research paper postulates common causes of headaches and sleep problems. We have highlighted the importance of good sleep in preventing tension headaches and migraines in previous articles about tension headaches (here), circadian rhythm (here) and the right amount of sleep (here). Many headache sufferers notice the impact of a poor night’ sleep right away, commonly experiencing headaches the next day.

New insights shed light on this connection. Before a migraine attack, especially with aura, a wave of neural excitation spreads through the brain. During this state, the perivascular spaces can close for several minutes. This could halt the movement of brain fluid needed to clear toxins. Clearance of toxic substances comes to a standstill for a period that might not seem that lengthy, but is long enough to be dangerous for sensitive neural systems. The result is damage to nerve cells, which can trigger a migraine attack.

Chronic migraine and medication overuse: the role of the glymphatic system

A 2024 study from Taiwan used advanced imaging techniques to understand better the glymphatic system's role in migraines and medication-overuse headaches.  Researchers examined the structures and functions of the glymphatic system and the draining lymphatic vessels in the meninges, which is where the glymphatic clearance flow merges with the body's lymphatic system. They found reduced functionality in these areas in people with chronic migraines, more so than in those with episodic migraines. The impairment was most pronounced in people who developed medication-overuse headaches in addition to chronic migraines. This aligns with observations that the impact of migraines on brain cleaning worsens with attack frequency.

The study also found that impairments correlated with other clinical parameters, such as headache intensity, migraine-related disability, and sleep quality. The authors also found evidence that high usage of headache medication can adversely affect brain cleaning.

Proven strategies and new perspectives in prevention and treatment

These findings raise radically new questions. For instance, could treating sleep disorders stabilize the glymphatic system and in that way help prevent headaches? Further research might uncover additional therapeutic approaches to positively impact brain cleaning. In the quest for effective and sustainable headache prevention, the research investigating the brain's ingenious cleaning mechanism supports the hypothesis that affected individuals should put regular, restorative sleep at the heart of their preventive efforts.