Summary: Researchers have discovered a safe, non-invasive way to enhance the brain’s waste clearance system by mechanically stimulating lymphatic vessels just beneath the facial skin. This gentle technique significantly improves cerebrospinal fluid (CSF) drainage—a critical function that declines with age and contributes to cognitive disorders like Alzheimer’s.
The team used fluorescent tracers in mice and monkeys to uncover a new drainage pathway connecting facial lymphatics to deep lymph nodes, which remains intact even in older individuals. A handheld device that lightly strokes the skin restored youthful CSF flow in aged animals, opening up exciting potential for wearable treatments that prevent or slow neurological decline.
Key Facts:
- New Drainage Route: Scientists mapped a previously unknown CSF drainage pathway through facial lymphatics to submandibular nodes.
- Non-Invasive Method: Gentle mechanical stimulation of the face and neck enhanced CSF clearance without drugs or surgery.
- Age-Proof Vessels: Superficial facial lymphatics retain function in aging, making them ideal targets for therapeutic stimulation.
Source: Institute for Basic Science
Scientists at the Institute for Basic Science (IBS) have uncovered a non-invasive method to boost the brain’s natural waste drainage system—a discovery that could open new avenues for tackling age-related neurological disorders.
In a study published in Nature, researchers from the IBS Center for Vascular Research, led by Director KOH Gou Young, along with senior researchers JIN Hokyung, YOON Jin-Hui, and principal researcher HONG Seon Pyo, demonstrated that precisely stimulating the lymphatics under skin on the neck and face can significantly enhance the flow of cerebrospinal fluid (CSF)—the liquid that cushions the brain and helps remove toxic waste—through lymphatic vessels.
Credit: Neuroscience News
This offers a new approach to clearing brain waste using safe, non-invasive mechanical stimulation, rather than relying on drugs or surgical interventions.
The human brain produces waste at a high rate compared to other organs, and clearing it efficiently is essential for healthy brain function. This clearance is primarily carried out by CSF, which removes harmful substances such as amyloid-β and tau proteins—key factors in Alzheimer’s and other neurodegenerative diseases. However, as we age, this drainage slows down, contributing to cognitive decline.
The IBS Center for Vascular Research previously published landmark studies in Nature (2019 and 2024) demonstrating that CSF drains to deep cervical lymph nodes via meningeal lymphatic vessels at the base of the skull and the nasopharyngeal lymphatic plexus. They also showed that age-related degeneration of these lymphatics impairs CSF clearance.
Furthermore, the team found that CSF drainage could be enhanced or suppressed pharmacologically by targeting cervical lymphatic vessels outside the skull. However, clinical applications remained limited because these lymphatics are located too deep in the neck for non-invasive access.
“This research not only completed the map of cerebrospinal fluid drainage pathways that clear brain waste, but also provided a new method to enhance CSF drainage from outside the brain,” stated KOH Gou Young, Center Director and corresponding author.
“We expect this will serve as a milestone for future research on neurodegenerative diseases including dementia.”
Now, using genetically modified mice and monkeys with fluorescent tracers, the researchers have mapped out a new CSF drainage route from the brain to superficial cervical lymph nodes—via a network of lymphatic vessels in the face, nose, and hard palate.
In older animals, many of these routes had degenerated—except for the vessels just beneath the facial skin, which retained full functionality despite aging.
“We confirmed that lymphatic vessels beneath facial skin connect to submandibular lymph nodes through various pathways,” explained JIN Hokyung, Senior Researcher and co-first author.
“Through these connections, we can regulate the reduced cerebrospinal fluid drainage function seen in aging and neurodegenerative diseases. Further research is needed to determine how this newly identified pathway can be applied in actual patients.”
Recognizing this, the team developed a force-regulated mechanical stimulator—a handheld device that gently presses and strokes the skin in a controlled manner. When applied to aged mice, the device restored CSF clearance to youthful levels, dramatically improving drainage without disrupting natural lymphatic contractions.
“I am pleased that we found a safer and more effective method to enhance cerebrospinal fluid drainage from outside the skull,” said YOON Jin-Hui, co-first author and neurovascular physiologist.
“We are conducting follow-up studies to investigate how this newly identified drainage pathway is altered in various brain disease patients and how this new stimulation method can be applied therapeutically.”
This technique could pave the way for wearable or clinical devices that enhance brain waste clearance in older adults or patients with neurological conditions.
The team is now investigating how this drainage system behaves in diseases like Alzheimer’s—and whether mechanical stimulation could serve as a preventive or therapeutic tool.
About this neuroscience research news
Author: William Suh
Source: Institute for Basic Science
Contact: William Suh – Institute for Basic Science
Image: The image is credited to Neuroscience News
Original Research: Open access.
“Increased CSF drainage by non-invasive manipulation of cervical lymphatics” by KOH Gou Young et al. Nature
Abstract
Increased CSF drainage by non-invasive manipulation of cervical lymphatics
Cerebrospinal fluid (CSF) in the subarachnoid space around the brain drains to lymph nodes in the neck, but the connections and regulation have been challenging to identify.
Here we used fluorescent tracers in Prox1–GFP lymphatic reporter mice to map the pathway of CSF outflow through lymphatics to superficial cervical lymph nodes.
CSF entered initial lymphatics in the meninges at the skull base and continued through extracranial periorbital, olfactory, nasopharyngeal and hard palate lymphatics, and then through smooth muscle-covered superficial cervical lymphatics to submandibular lymph nodes.
Tracer studies in adult mice revealed that a substantial amount of total CSF outflow to the neck drained to superficial cervical lymph nodes.
However, aged mice had fewer lymphatics in the nasal mucosa and hard palate and reduced CSF outflow to cervical lymph nodes.
Superficial cervical lymphatics in aged mice had increased endothelial cell expression of Nos3, encoding endothelial nitric oxide synthase (eNOS), but had less eNOS protein and impaired nitric oxide signalling.
Manipulation of superficial cervical lymphatics through intact skin by a force-regulated mechanical device doubled CSF outflow and corrected drainage impairment in aged mice.
This manipulation increased CSF outflow by compressing superficial cervical lymphatics while having little effect on their normal spontaneous contractions.
Overall, the findings highlight the importance of superficial cervical lymphatics for CSF outflow and the potential for reversing CSF drainage impairment by non-invasive mechanical stimulation.
