Inside the brain’s night shift: Sleep research on biological ‘wash cycle’ shows promise

SINGAPORE – The 2026 World Sleep Day treats sleep as seriously as diet and exercise with its new “sleep well, live better” theme.

The rallying call is built around a simple premise: Sleep is not a luxury but an everyday health behaviour that shapes how well people think, feel and age.

World Sleep Day is the official campaign arm of World Sleep Society. It has been organised by the non-profit group since 2008, and is described as a global call to action by the US-based society.

Just as societies plan for clean water or safe food, people also need to plan for regular, good-quality sleep to boost brain health, say sleep experts and advocates.

But sleep is more than just about rest and memory consolidation. It is also a time for the brain’s glymphatic system to kick into high gear.

This is the body’s neural waste removal mechanism, which clears out toxic proteins and metabolic waste produced during the day.

It works mainly during deep sleep, when clear brain fluid called cerebrospinal fluid (CSF) flows through brain tissues, washing away waste and carrying it into veins to be removed.

In December 2025, Monash University in Melbourne, Australia, reported that a team of scientists – led by Professor Natalie Trevaskis and collaborating with Yale School of Medicine in the US – developed a non-invasive way to boost the brain’s lymphatic “clean-up” system to improve recovery after ischaemic stroke and other neurological diseases.

The lymphatic system cleans waste from most of the body, while the glymphatic system is the brain’s own version, using fluid around blood vessels during deep sleep to wash waste out of brain tissue.

An ischaemic stroke occurs when a blood clot or fatty plaque blocks an artery supplying blood to the brain, cutting off oxygen and nutrients, causing brain cells to die.

The team used gentle, externally applied stimulation over the neck to activate lymphatic drainage pathways that help carry waste fluid away from the brain after a stroke.

Early animal and imaging work suggests this approach can enhance the brain’s own clearance system without surgery or drugs, though it is still far from routine clinical use.

This is a promising proof‑of‑concept but not a near‑term cure.

While it gives an intriguing glimpse of future stroke care, for now, the most powerful glymphatic support most can reliably access is still regular good-quality sleep, say sleep science specialists.

Harvard’s early-stage lab work

Over at Harvard University’s Wyss Institute, Dr Katharina Meyer tells The Straits Times over e-mail that her team is using engineered human brain models to probe how a disrupted “clean-up” system might contribute to brain disease, rather than directly running glymphatic trials in patients.

She is a senior scientist for Biologically Inspired Engineering at Harvard, where she develops human stem cell-derived 3D brain models to study neurodegenerative, neuroinflammatory diseases and bipolar disorder. Trained in biophysics and molecular biomedicine in Germany, she moved to Harvard Medical School for post-doctoral research on brain ageing, Alzheimer’s disease and neuropsychiatric disorders.

The institute is a cross-disciplinary research institute at the university focusing on biologically inspired engineering – using principles from nature to design new technologies for health and the environment.

It operates like a hybrid between an academic laboratory and a research-and-development outfit, geared towards turning high-risk scientific ideas into commercial products, start-ups and therapies to benefit mankind.

Harvard University is at the forefront of synthetic biology, engineering diverse cell types and tissues, including components of the glymphatic system, to study their effects on neurological diseases.

At the institute, Dr Meyer is part of a team working on the early discovery side, rather than running clinical trials.

Scientists there develop complex 3D brain organoids, which are tiny, laboratory-grown human brain cells from stem cells, then add simple vessel-like structures and supporting brain cells to better mimic how real brain tissue sits next to blood vessels.

This vascularised set-up is designed to allow miniature brains in a dish to establish their own drainage-like pathways so researchers can study waste clearance and fluid flow under controlled conditions.​

This allows the group to control and manipulate fluid flow around organoids and to see how changes in waste clearance and stress-related signals affect the brain-like tissue.

By bringing these approaches together, the team hopes to link very basic processes in the brain’s waste-clearance system to the reality of clinical conditions such as stroke, dementia and bipolar disorder, based on the understanding that this research is still at an early stage.

Dr Meyer prefers to call the glymphatic system the “night-shift cleaning crew”.

“The brain has no classic lymphatic system, so it uses clear fluid flowing along blood vessels to rinse away waste proteins, toxins and excess fluid from between brain cells. This ‘wash-through’ helps remove substances linked to stroke damage and neurodegenerative diseases,” she says.

“Deep, restorative sleep is when this system is most active. During deep sleep, brain cells shrink slightly, opening more space between them so fluid can circulate more easily and carry waste away,” she adds.

“Most of this housekeeping work happens during deep sleep, which is why regular, high-quality sleep is so important for brain health over the long term. This process is also fine-tuned by our internal body clock, so chronic insomnia or disrupted circadian rhythms may interfere with the brain’s natural clean-up over time.”

New findings in research

What is exciting about the Monash-Yale report published in 2025 is that it shows that the team has moved from simply observing the brain’s drainage system to trying to support it as a treatment strategy, says Dr Meyer.

It highlights a new target after a stroke that is not just about removing the blood clot, but also about clearing the toxic molecules and excess fluid that remain in the brain afterwards.

It also explores non-invasive ways to stimulate drainage pathways in the neck and suggests there may be gender differences in these vessels. This could help explain why diseases such as stroke and Alzheimer’s often affect women differently, even after accounting for their longer life expectancy, which is why researchers are currently probing gender-specific differences in the brain’s waste-drainage systems.

Data from the Geneva-based World Stroke Organization shows that women bear a higher lifetime risk and often worse outcomes than men from both stroke and Alzheimer’s.

The group’s 2025 Global Stroke Fact Sheet pulls together data from 1990 to 2021, showing that women account for roughly half of people living after a stroke and about half of stroke deaths and disability worldwide, with a higher lifetime stroke risk than men. Alzheimer’s work over the past couple of decades also shows that about two‑thirds of people living with Alzheimer’s are women, and that women’s lifetime risk is higher, even after you factor in longer life expectancy.

“For stroke, I would say we are at an advanced preclinical and imaging stage, but not yet at dedicated glymphatic-targeted add-on trials in patients,” Dr Meyer says.

“Reviews and preclinical work strongly suggest that the glymphatic and meningeal lymphatic systems are promising therapeutic targets, and several groups are actively exploring them in animal models and with advanced imaging in humans.”

The meningeal lymphatic system refers to three thin layers of tissue that protect the brain and spinal cord.

“On that basis, I expect to see more structured early-phase clinical studies over the next few years, most likely as add-ons to standard treatments such as clot-busting drugs or mechanical clot removal, rather than standalone therapies.”

She says that turning any of these approaches into routine care is a longer journey. To reduce long-term dementia risk, the horizon is likely even further out because doctors need reliable ways to measure glymphatic function in people and then to prove that altering it truly changes disease risk, not just through laboratory markers.

“This is still early-stage research,” Dr Meyer points out, as large clinical trials showing clear benefits on real-world outcomes such as better functional recovery and independence after a stroke typically take years from the first promising human data.

“Much of the evidence comes from animal models or small human studies. We do not yet know which patients will benefit most, what the ideal ‘dose’ of stimulation is, or whether pushing this system too hard could, in some situations, worsen swelling or inflammation.

“For conditions beyond stroke, such as dementia, the datasets are even more preliminary, so it is important to be hopeful but cautious.”

Unclogging the brain’s drainage system in Singapore

In Singapore, surgeons are now testing whether a delicate neck operation can help “unclog” the brain’s night-time cleaning system and slow diseases such as dementia.

At the National Neuroscience Institute (NNI), neurosurgery consultant Chen Min Wei says the institute is running a clinical trial built around the glymphatic system, with other public hospitals also moving into this space.

This trial was conceptualised based on the findings of ground-breaking research, such as that from Monash and Yale, as well as the anatomical knowledge of how glymphatic fluid eventually drains into the lymph nodes of the neck.

“By performing an established surgical procedure called lymphaticovenous bypass in the neck – which involves connecting lymphatic vessels in the neck with neighbouring veins – we aim to improve the downstream (neck) clearance of glymphatic fluid. The postulation is that this will improve the flow of glymphatic fluid in the brain, resulting in improved clearance of neurotoxins,” says Dr Chen.

“Our research is part of a larger global effort, mainly in Asia, to explore surgery as a means to positively influence diseases such as dementia and neurodegeneration. So far, the early results are promising, and we await longer-term results.”

Associate Professor Adeline Ng, from SingHealth Duke-NUS Academic Medical Centre’s Neuroscience Academic Clinical Programme, notes that the Monash-Yale research findings on mice fills in crucial anatomical details of the brain’s drainage routes. The research shows how cerebrospinal fluid can reach neck lymph nodes within minutes via meningeal lymphatic vessels.

But at the same time, Prof Ng stresses that directly tracking this drainage in people is technically difficult and will likely depend on specialised magnetic resonance imaging (MRI) scans, such as the one used in the Monash-Yale study.

“Such techniques allow for visualisation of how the contrast dye is drained by the brain’s ‘drainage system’ into the lymph nodes in the neck,” says Prof Ng, who is also a senior consultant of neurology at NNI.

Prof Ng says these observations are essential, but it is worth noting that such studies require the use of contrast which can carry risk in some people, therefore it is not routinely used for research studies.

She adds that NNI is studying the use of standard non-contrast MRI to track the efficiency of fluid clearance from the brain and matching the MRI results to the memory test scores in patients with Alzheimer’s type of dementia.

The authors in the Monash-Yale study also speculate about the potential differences and implications of a smaller size of the drainage system – the meningeal lymphatic volume in female patients.

But it is important to consider caveats such as the small sample size and these studies need to be replicated in a larger study, Prof Ng highlights.

“More studies with larger numbers of patients and healthy persons acting as ‘controls’ incorporating the use of the MRI techniques developed by the authors is needed. This is to allow us to reliably discriminate between the effects of sex, age and disease on the brain’s drainage architecture.”