Press Releases & Research Commentary

Maiken Nedergaard, M.D., D.M.Sc. has been awarded the International Prize for Translational Neuroscience of the Gertrud Reemtsma Foundation for her research in the glymphatic system, the brain's unique waste removal process.

Nedergaard's research was recognized by the Foundation for findings that "offer new approaches for treatments and preventive measures for Alzheimer's and other neurodegenerative diseases."

First discovered by researchers in the URMC Center for Translational Neuromedicine in 2012, the glymphatic system piggybacks on blood vessels and pumps cerebrospinal fluid, washing waste from the brain. The accumulation of toxic proteins like beta amyloid are linked neurological disorders, including Alzheimer's disease. Nedergaard's lab has since gone on to show how sleep disruption, age, and injury can impair the brain's ability to effectively remove waste.

Nedergaard was presented the award at a ceremony at the Max Plank Society in Cologne, Germany on September 10.

New research details how the complex set of molecular and fluid dynamics that comprise the glymphatic system -- the brain's unique process of waste removal -- are synchronized with the master internal clock that regulates the sleep-wake cycle. These findings suggest that people who rely on sleeping during daytime hours are at greater risk for developing neurological disorders.

"These findings show that glymphatic system function is not solely based on sleep or wakefulness, but by the daily rhythms dictated by our biological clock," said neuroscientist Maiken Nedergaard, M.D., D.M.Sc., co-director of the Center for Translational Neuromedicine at the University of Rochester Medical Center (URMC) and senior author of the study, which appears in the journal Nature Communications.

The findings add to a growing understanding of the operation and function of glymphatic system, the brain's self-contained waste removal process which was first discovered in 2012 by researchers in the Nedergaard's lab. The system consists of a network of plumbing that follows the path of blood vessels and pumps cerebrospinal fluid (CSF) through brain tissue, washing away waste. Research a few years later showed that the glymphatic system primarily functions while we sleep.

Since those initial discoveries, Nedergaard's lab and others have shown the role that blood pressure, heart rate, circadian timing, and depth of sleep play in the glymphatic system's function and the chemical signaling that occurs in the brain to turn the system on and off. They have also shown how disrupted sleep or trauma can cause the system to break down and allow toxic proteins to accumulate in the brain, potentially giving rise to a number of neurodegenerative diseases, such as Alzheimer's.

Each of us carts around a 3-lb. universe that orchestrates everything we do: directing our conscious actions of moving, thinking and sensing, while also managing body functions we take for granted, like breathing, keeping our hearts beating and digesting our food. It makes sense that such a bustling world of activity would need rest. Which is what, for decades, doctors thought sleep was all about. Slumber was when all the intricate connections and signals involved in the business of shuttling critical brain chemicals around went off duty, taking time to recharge. We're all familiar with this restorative role of sleep for the brain--pulling an all-nighter or staying awake during a red-eye flight can not only change our mood, but also affect our ability to think clearly until, at some point, it practically shuts down on its own. When we don't get enough sleep, we're simply not ourselves.

Yet exactly what goes on in the sleeping brain has been a biological black box. Do neurons stop functioning altogether, putting up the cellular equivalent of a Do Not Disturb sign? And what if a sleeping brain is not just taking some well-deserved time off but also using the downtime to make sense of the world, by storing away memories and captured emotions? And how, precisely, is it doing that?

A year later, a biological explanation for why poor sleep might be linked to Alzheimer's emerged. Dr. Maiken Nedergaard, co-director of the Center for Translational Neuromedicine at the University of Rochester, identified a previously ignored army of cells that is called to duty during sleep in the brains of mice and acts as a massive pump for sloshing fluid into and out of the brain. This plumbing system, which she dubbed the "glymphatic system" (it works in parallel to the lymph system that drains fluid from other tissues in the body), seemed to perform a neural rinsing of the brain, swishing out the toxic proteins generated by active neurons (including those amyloid fragments) and clearing the way for another busy daily cycle of connecting and networking.

Taken together with Holtzman's discovery that levels of amyloid spiked during the day and dropped during sleep, Nedergaard's findings gave further credence to the theory that sleep might perform a housekeeping function critical for warding off diseases like Alzheimer's. "These results very much support the notion that one of the roles of sleep is to actually accelerate the clearance of beta amyloid from the brain," says Nora Volkow, director of the U.S. National Institute on Drug Abuse.

A new study shows that when specific human brain cells are transplanted into animal models of multiple sclerosis and other white matter diseases, the cells repair damage and restore function. The study provides one of the final pieces of scientific evidence necessary to advance this treatment strategy to clinical trials.

"These findings demonstrate that through the transplantation of human glial cells, we can effectively achieve remyelination in the adult brain, " Steve Goldman, M.D., Ph.D., professor of Neurology and Neuroscience at the University of Rochester Medical Center (URMC), co-director of the Center for Translational Neuromedicine, and lead author of the study. "These findings have significant therapeutics implications and represent a proof-of-concept for future clinical trials for multiple sclerosis and potential other neurodegenerative diseases."

The findings, which appear in the journal Cell Reports, are the culmination of more than 15 years of research at URMC understanding support cells found in the brain called glia, how the cells develop and function, and their role in neurological disorders.

Goldman's lab has developed techniques to manipulate the chemical signaling of embryonic and induced pluripotent stem cells to create glia. A subtype of these, called glial progenitor cells, gives rise to the brain's main support cells, astrocytes and oligodendrocytes, which play important roles in the health and signaling function of nerve cells.

Maiken Nedergaard, M.D., D.M.Sc., co-director of the Center for Translational Neuromedicine, professor in the Departments of Neurology, Neuroscience and Neurosurgery, received the Thomas Willis Lecture Award from the American Stroke Association. The award honors Nedergaard's career of significant contributions to the basic science of stroke research.

The Nedergaard lab is dedicated to deciphering the role of neuroglia, cell types that constitute half of the entire cell population of the brain and spinal cord.

Last month, the lab published research showing that during a stroke the glymphatic system goes awry, triggers edema and drowns brain cells. In 2012, Nedergaard and her colleagues first described the glymphatic system, a network that piggybacks on the brain's blood circulation system and is comprised of layers of plumbing, with the inner blood vessel encased by a 'tube' that transports cerebrospinal fluid (CSF). The system pumps CSF through brain tissue, primarily while we sleep, washing away toxic proteins and other waste.

The Thomas Willis Award honors the prominent British physician credited with providing the first detailed description of the brain stem, the cerebellum and the ventricles, with extensive hypothesis about the functions of these brain parts. The award recognizes contributions to the investigation and management of stroke basic science.

Nedergaard was one of eleven leading scientists honored for their work by the American Stroke Association. The awards were given during the American Stroke Association's International Stroke Conference in Los Angeles.

Cerebral edema, swelling that occurs in the brain, is a severe and potentially fatal complication of stroke. New research, which was conducted in mice and appears in the journal Science, shows for the first time that the glymphatic system -- normally associated with the beneficial task of waste removal -- goes awry during a stroke and floods the brain, triggering edema and drowning brain cells.

"When you force every single cell, which is essentially a battery, to release its charge it represents the single largest disruption of brain function you can achieve -- you basically discharge the entire brain surface in one fell swoop," said Humberto Mestre, M.D., a Ph.D. student in the Nedergaard lab and lead author of the study. "The double hit of the spreading depolarization and the ischemia makes the blood vessels cramp, resulting in a level of constriction that is completely abnormal and creating conditions for CSF to rapidly flow into the brain."