New research sheds light on how sleep helps the brain to clean itself, raising concerns about how a widely used sleep aid may interfere with this process.
Scientists have long believed that sleep acts as a cleaning system for the brain, allowing special fluids to flush out waste that accumulates during waking hours. However, the mechanics behind this process remained unclear.
A study published in the journal Cell reveals that rhythmic contractions of blood vessels, driven by a chemical similar to adrenaline, may play a key role in pushing these fluids through the brain.
Discovery of the Glymphatic System
The brain lacks the lymphatic vessels that clear fluid in other body parts. Instead, researchers discovered in 2012 that cerebrospinal fluid—a liquid that surrounds the brain—flows through tiny pathways near blood vessels.
This system, known as the glymphatic system, works most actively during sleep, carrying away harmful molecules and waste. Dysfunction in this system has been linked to conditions like Alzheimer’s disease.
How the brain gets rid of its chemical waste through the glymphatics during sleep, via blood vessel oscillations, regulated by norepinephrine. Impeded by Ambien.https://t.co/0Pqg2lh28r @CellCellPress https://t.co/EPyqafXJHW @ScienceMagazine pic.twitter.com/neB4p5bq2e
— Eric Topol (@EricTopol) January 9, 2025
In the new study, neuroscientist Maiken Nedergaard and her University of Rochester Medical Center team explored what drives cerebrospinal fluid to circulate. They implanted electrodes and fiber optic filaments into mice, allowing the animals to sleep naturally while the researchers tracked brain activity, blood flow, and fluid movement.
Their findings showed that during non-REM sleep—a stage critical for tissue repair—levels of norepinephrine, a chemical similar to adrenaline, fluctuate in regular cycles, peaking every 50 seconds.
These cycles cause blood vessels in the brain to contract and relax rhythmically. The researchers observed that cerebrospinal fluid followed this pattern, moving more efficiently during non-REM sleep unlike wakefulness or REM sleep, which is associated with memory processing.
Testing the fluid flow mechanism
To confirm the role of blood vessel movements, the scientists injected a glowing molecule into the mice to track cerebrospinal fluid flow. They then artificially sped up norepinephrine cycles, increasing blood vessel pulses from every 50 seconds to every 10 seconds. This enhanced fluid penetration into deeper brain areas.
The contraction and relaxation of blood vessels act like a pump. As vessels contract, cerebrospinal fluid flows in to fill the space, and when they relax, it is pushed further along.
The study also tested the impact of zolpidem, a common sleep medication sold under the name Ambien. Researchers found that the drug disrupted norepinephrine cycles and reduced cerebrospinal fluid flow in the mice.
While zolpidem is widely used, Nedergaard and other experts cautioned against immediate alarm. This study doesn’t mean people should stop taking their sleep medication, said researcher Olaia Lewis. However, it does highlight the need for further studies in humans to determine if these effects occur in people.
These findings emphasize the complexity of sleep and its critical role in brain health. Researchers hope the study will lead to new sleep aids that support, rather than disrupt, the brain’s natural cleaning system.
