A recent study has conclusively demonstrated the presence of a system previously theorized to remove metabolic waste from the human brain. The research utilizes imaging techniques on neurosurgery patients to illustrate how the brain’s glymphatic system operates and suggests that certain lifestyle choices can enhance its function.
For years, scientists have speculated about a network of pathways in the brain that help eliminate metabolic proteins, which could accumulate and potentially cause Alzheimer’s and other types of dementia. However, evidence of this network in humans had remained elusive until now.
This fresh study involved five patients who were undergoing brain surgery at Oregon Health & Science University, providing the first images of this network of perivascular spaces—fluid-filled structures surrounding arteries and veins in the brain.
“No one has definitively shown this before,” remarked senior author Juan Piantino, M.D., an associate professor of pediatrics (neurology) at OHSU School of Medicine and a member of the Neuroscience Section at the Papé Family Pediatric Research Institute. “I had my doubts as well, and many others still do. This finding is truly groundbreaking.”
The findings were published today in the Proceedings of the National Academy of Sciences.
The research combined an injection of an inert contrasting agent with a specialized magnetic resonance imaging method to trace the flow of cerebrospinal fluid through specific pathways in the brain at intervals of 12, 24, and 48 hours post-surgery. This study provides definitive evidence of an efficient waste-clearance mechanism in the human brain, reinforcing the importance of lifestyle changes and medications currently under development to maintain and improve this system.
“This indicates that cerebrospinal fluid does not just randomly enter the brain, as if soaking a sponge in a bucket,” Piantino explained. “It travels through designated channels.”
More than ten years ago, researchers at the University of Rochester proposed that the brain contains a network of waste-clearance pathways similar to the lymphatic system in the body, which is part of the immune system. They confirmed this through real-time imaging of live mice, coining the term “glymphatic system” due to its reliance on glial cells.
However, confirmation of the glymphatic system’s existence through imaging in humans had yet to occur.
Identifying pathways in patients
The recent study involved five patients at OHSU who had tumors removed between 2020 and 2023. Each patient consented to receive a gadolinium-based inert contrasting agent injected through a lumbar drain, a standard part of the surgical procedure for tumor removal, allowing the tracer to mix with cerebrospinal fluid and enter the brain.
Subsequently, each patient underwent magnetic resonance imaging (MRI) at various points to track the flow of cerebrospinal fluid.
The images revealed that fluid did not spread uniformly through the brain; instead, it moved along specific pathways through the perivascular spaces. Researchers documented these findings using a specialized type of MRI known as fluid-attenuated inversion recovery (FLAIR), which, unlike standard MRI sequences, highlighted the gadolinium tracer in the brain.
“That was pivotal,” Piantino stated.
“You can visibly see the previously dark perivascular spaces light up,” noted co-lead author Erin Yamamoto, M.D., a neurological surgery resident at OHSU. “The imaging was strikingly similar to that which the Rochester group used in mice.”
Removing waste from the brain
Researchers believe this network effectively helps eliminate metabolic waste produced by the brain’s energy-intensive activities. This waste includes proteins like amyloid and tau, which can form clumps and tangles seen in the brains of Alzheimer’s patients.
Emerging studies indicate that certain medications could be beneficial, but much attention to the glymphatic system has focused on lifestyle changes to improve sleep quality, such as keeping a consistent sleep schedule, creating a relaxing bedtime routine, and avoiding screens before sleep. Researchers suggest that during deep sleep, a properly functioning glymphatic system efficiently transports waste proteins towards veins that exit the brain.
“Though many suspected the importance of these perivascular spaces, it was never proven until now,” said Piantino.
The authors of the study acknowledged the late Justin Cetas, M.D., Ph.D., who initiated this research as a neurosurgeon at OHSU before moving to chair of neurological surgery at his alma mater, the University of Arizona Health Sciences Center in Tucson. Tragically, he passed away in a motorcycle accident in 2022.
