From New Scientist magazine:
The glymphatic system is the brain’s recently discovered network for flushing out toxins. Now, we’re uncovering surprising ways to boost it to protect brain health
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Why sleep is key to cleaning the brain
In 2013, Maiken Nedergaard at the University of Rochester in New York state and her team, which included Iliff, injected a green tracer into the cerebrospinal fluid of sleeping mice and watched it stream around the brain. After the mice were gently woken, this flow fell by about 95 per cent. The researchers also showed that beta-amyloid, a key waste product associated with Alzheimer’s disease, was cleared roughly twice as fast when the mice were asleep.
Then last year, Natalie Hauglund, a sleep scientist now at the University of Oxford, and her colleagues helped identify a control mechanism. Studying mice, they showed that concentrations of the neurotransmitter noradrenaline rose and fell about every 50 seconds during non-REM sleep. This caused arteries in the brain to alternately swell and constrict, gently pumping the fluid along the outside.
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Boosting glymphatic clearance in the brain
In theory, then, we may be able to intervene to ensure people’s glymphatic systems work better to prevent such conditions. While there’s currently no approved treatment that does so, several interventions are being explored.
One uses near-infrared light, which is invisible to the naked eye but can penetrate flesh and bone, reaching deep into the brain, where it alters cellular functions and affects pathways involved in inflammation and vascular function. A 2022 review described evidence from animal experiments that transcranial near-infrared light could help treat neurodegenerative conditions, possibly by changing the shape of blood vessels and astrocytes to improve glymphatic flow. However, “we do not yet know that near-infrared light directly increases glymphatic flow in humans”, says Bill.
There are hints it might. In one study, 57 people who had been diagnosed with or showed symptoms of dementia wore a near-infrared light helmet for 6 minutes twice daily for eight weeks and showed some small cognitive improvements. One participant saw an 80 per cent improvement in their ability to draw a clock, for example, while others showed better learning and memory. Results varied considerably across the group, though, leaving uncertainty about how well the treatment works.
Another pilot study tested a headset developed by Canadian company Vielight, which delivers near-infrared light to the brain through the skull and nose. After 12 weeks of regular use, the five participants showed improvements in cognitive tests, while caregivers reported better sleep and less anxiety. But with no placebo group and a larger trial suspended because of recruitment difficulties, the evidence is still too thin to justify buying your own red-light therapy device for home use.
Another approach uses focused ultrasound with microbubbles. Researchers inject tiny bubbles into a vein, where they travel to the brain. Focused ultrasound waves are aimed at the head, which causes the microbubbles to vibrate, jostling blood vessels, changing the flow of glymphatic fluids around them. In mice, this can accelerate the removal of beta-amyloid from the brain.
Meanwhile, Sephira Ryman at the University of New Mexico in Albuquerque has been experimenting with a different way to get brain vessels pumping – carbon dioxide. If people alternate between inhaling high doses of CO2 for about 30 seconds and breathing normal air, it seems to improve the clearance of harmful proteins from the brain. The extra CO2 causes blood vessels in the brain to widen, while switching back to regular air allows them to narrow, thus generating the pumping motion needed for glymphatic function – echoing what happens during sleep.
This isn’t safe to try at home: inhaling CO2 is extremely dangerous. However, when carried out under the watchful eye of Ryman and her colleagues, this simple technique can help remove alpha-synuclein, a protein that seems to contribute to Parkinson’s. At a conference in July, Ryman reported similar findings for beta-amyloid. Together, they offer some of the most tantalising signs that we may be able to boost clearance in people – although whether doing so protects their brain health is still unknown.
Ultimately, Bill would like to develop “a statin for the brain”: a medication that would enhance the blood vessel-driven pumping in older people. “You could take a pill before you went to bed and open up your sluice gates, and the fluid would flow away,” she says.
A study published in March, which Iliff worked on, hints at this possibility. Older adults without any brain-related conditions received the drugs midodrine and dexmedetomidine, which increase the pulsing of blood vessels in the brain. During a single sleep, clearance of tau and beta-amyloid increased by about 10 per cent – although the findings await peer review.
Full article: Can we harness the brain’s deep-cleaning system to prevent Alzheimer’s?