New Study Reveals Brain's Waste-Clearance Pathways for the First Time

Scientists have long speculated about a mysterious network of pathways in the brain that are thought to clear metabolic proteins and prevent the development of Alzheimer’s and other forms of dementia.

Now, a groundbreaking study involving five patients undergoing brain surgery at Oregon Health & Science University has unveiled this elusive network of perivascular spaces – fluid-filled structures along arteries and veins – within the brain. This discovery has the potential to revolutionize our understanding of brain health and neurodegenerative diseases.

“Nobody has shown it before now,” said senior author Juan Piantino, M.D., associate professor of pediatrics (neurology) in the OHSU School of Medicine and a faculty member of the Neuroscience Section of the Papé Family Pediatric Research Institute at OHSU. “I was always skeptical about it myself, and there are still a lot of skeptics out there who still don’t believe it. That’s what makes this finding so remarkable.”

The study employed a combination of an inert contrasting agent and specialized magnetic resonance imaging to track the flow of cerebrospinal fluid through specific brain pathways at 12, 24, and 48 hours post-surgery. By definitively demonstrating the presence of an efficient waste-clearance system within the human brain, this study advocates for the promotion of lifestyle interventions and medications aimed at preserving and enhancing this system.

“This shows that cerebrospinal fluid doesn’t just get into the brain randomly, as if you put a sponge in a bucket of water,” Piantino said. “It goes through these channels.”

Over a decade ago, scientists at the University of Rochester proposed the existence of a waste-clearance network in the brain resembling the body’s lymphatic system. This theory was later confirmed through real-time imaging of live mice brains. Dubbed the “glymphatic system” due to its reliance on glial brain cells, this discovery represented a significant milestone.

However, until now, the existence of the glymphatic system in humans has not been confirmed through imaging.

In the new study, researchers at OHSU have uncovered fascinating insights into the behavior of cerebrospinal fluid in the human brain. By examining five patients who underwent neurosurgery to remove brain tumors, the researchers made a stunning discovery.

Using a gadolinium-based inert contrasting agent injected through a lumbar drain, the researchers were able to track the movement of cerebrospinal fluid in the brain with unprecedented precision. They found that instead of diffusing uniformly, the fluid followed distinct pathways through perivascular spaces, revealing a complex network of channels within the brain.

This research, documented using a specialized MRI technique called fluid-attenuated inversion recovery (FLAIR), has the potential to revolutionize our understanding of brain function and could have far-reaching implications for neurosurgical procedures.

“You can actually see dark perivascular spaces in the brain turn bright,” said co-lead author Erin Yamamoto, M.D., a resident in neurological surgery at the OHSU School of Medicine. “It was quite similar to the imaging the Rochester group showed in mice.”

The intricate network of pathways in our brain serves a crucial role in flushing out metabolic wastes, including proteins like amyloid and tau. These proteins have been linked to the development of clumps and tangles in the brains of Alzheimer’s patients. While research on medications is ongoing, much attention has been focused on lifestyle-based approaches to enhance the glymphatic system.

Maintaining a consistent sleep schedule, establishing a relaxing pre-sleep routine, and avoiding screens in the bedroom before bedtime are believed to promote a well-functioning glymphatic system. During deep sleep, this system efficiently transports waste proteins out of the brain through the exiting veins.

“People thought these perivascular spaces were important, but it had never been proven,” Piantino said. “Now it has.”