More than $4.5 million in new grants to the lab of University of Rochester Medical Center scientist Maiken Nedergaard, M.D., D.M.Sc., underscore the important role the brain's waste disposal system may play in a range of neurological disorders. The new awards will advance understanding of how small vessel disease and traumatic brain injury can give rise to cognitive and behavioral problems.
Nedergaard and her colleagues first unveiled the brain's unique method of removing waste - dubbed the glymphatic system - in a paper in Science Translational Medicine in 2012. The research revealed that the brain possesses a circulation network that piggybacks on blood vessels and uses cerebral spinal fluid to flush away waste products from brain tissue. Since that time, the team has gone on to show that the glymphatic system works primarily while we sleep, could be a key player in diseases like Alzheimer's, and is disrupted after traumatic brain injury.
The two new grants - $3.8 million from the National Institute of Neurological Disorders and Stroke (NINDS) and $769,000 from the Department of Defense - bring the total amount of funding received by Nedergaard's lab to study aspects of the glymphatic system to $13.4 million since 2012.
The new NINDS grant will explore the role of the glymphatic system in small vessel disease (SVD). The blood supply in the brain is delivered via a complex web of micro-vessels that permeate the brain. When blood flow is interrupted in these vessels, the result can be a mini-stroke which often goes undetected but nevertheless causes damage in nearby brain tissue. As these mini-strokes accumulate over time, the result can be a form of dementia.
Unlike regular strokes, which are triggered by clots that block blood flow in the vessels, scientists are not entirely sure what causes these mini-strokes. They do know that certain risk factors, such as hypertension, diabetes, and obesity, contribute to SVD.
Nedergaard speculates that the glymphatic system may play a role in these mini-strokes. Namely, the system is not working properly in these individuals, causing cerebral spinal fluid to accumulate which in turn triggers inflammation and interrupts blood flow.
The new Department of Defense grant will examine what occurs when the glymphatic system is disrupted. Prior research has shown that the system is delicate and can be impaired after head trauma. When this occurs, cellular waste products such as amyloid beta and tau which are normally cleared from the brain can accumulate, leading to cognitive and behavioral problems.
The research will have particular application to the military and the treatment of servicemen and women who experience cognitive difficulties after traumatic brain injury. The goal of the research is to develop a diagnostic test to determine glymphatic system impairment and identify treatments that could help repair the system.
Nedergaard is the co-director of the Center for Translational Neuromedicine, which maintains labs in both the University of Rochester and the University of Copenhagen.