The brain鈥檚 system for removing waste is driven primarily by the pulsations of adjoining arteries, 人妻少妇专区 neuroscientists and mechanical engineers report in a new study. They also show that changes in the pulsations caused by high blood pressure slow the removal of waste, reducing its efficiency.
This might explain the association between high blood pressure and Alzheimer鈥� disease, the researchers say. Alzheimer鈥檚, the most common cause of dementia among older adults, is characterized by abnormal clumps and tangled bundles of fibers in the brain.
The study, reported in , builds upon groundbreaking discoveries about the brain鈥檚 waste removal system by Maiken Nedergaard, co-director of the University鈥檚 . Nedergaard and her colleagues were the first to describe how cerebrospinal fluid is pumped into brain tissue and flushes away waste. Subsequent research by her team has shown that this glymphatic waste removal system is more active while we sleep and can be damaged by stroke and trauma.
This latest research shows 鈥渋n much greater depth and much greater precision than before鈥� how the glymphatic system functions in the perivascular spaces that surround arteries in the outer brain membrane, says and an expert in fluid dynamics. His lab is collaborating with Nedergaard鈥檚 team as part of a $3.2 million National Institute on Aging grant.
For this study, Humberto Mestre, a PhD student in Nedergaard鈥檚 lab, injected minute particles in the cerebrospinal fluid of mice, and then used two-photon microscopy to create videos showing the particles as they moved through the perivascular spaces.
Jeff Tithof, a postdoctoral researcher working with Kelley, then used an automated particle tracking code developed by the Kelley lab that can follow a dot from frame to frame of a video, and after a few frames estimate its velocity and acceleration. From a typical video spanning 鈥渢ens of minutes,鈥� the code could track more than 20,000 individual particles and derive about a million total measurements to quantify their movements, which show up as 鈥渃omet tails鈥� behind each of the tracked dots in the videos.
By analyzing videos from experiments involving multiple mice, 鈥渨e were able to gather a really rich data set of what鈥檚 actually happening with this flow,鈥� Kelley says.
The researchers found that:
- The flow of cerebrospinal fluid is synchronized with the heartbeat, as seen in the animation below. 鈥淥ne of the main points of this paper is that this flow is mostly 鈥� and maybe purely — driven by the flexing of the artery wall,鈥� Kelley says.
- When high blood pressure was induced in the mice, the flow slowed down and was not as efficient. Artery walls are muscular; they have to flex harder in order to hold the same shape when there鈥檚 more pressure inside, and they get stiffer,鈥� Kelley says. 鈥淎nd that changes the waveform of the flexing of the artery wall.鈥�
鈥淭hat’s highly interesting because early onset high blood pressure is known to be a risk factor for Alzheimer鈥檚 in humans,鈥� Kelley says. 聽鈥淭here are still a few steps between what we did and chronic high blood pressure. But it may be that high blood pressure鈥攂y reducing the pumping of cerebrospinal fluid so that waste isn鈥檛 cleared out as well — is one mechanism that leads to Alzheimer鈥檚.鈥�
The findings should resolve a debate among researchers about whether the flow of cerebrospinal fluid in the glymphatic system is in the same direction as arterial blood flow, as demonstrated by this paper, is opposite, or is random molecular diffusion, Kelley says. 鈥淭his is going to quell a lot of those debates.鈥�
The collaboration with Nedergaard also includes Department of Mechanical Engineering faculty members John Thomas (a coauthor of this paper) and Jessica Shang, along with Ali Ert眉rk with the Institute for Stroke and Dementia Research at Ludwig Maximilians University of Munich. Other coauthors of this paper include Ting Du, Wei Song, Weiguo Peng, Amanda Sweeney, and Genaro Olveda of Nedergaard鈥檚 lab.
Learn more about Rochester鈥檚 role in understanding the brain’s waste removal system.
Maiken Nedergaard was recently awarded the 2018聽聽for her work that led to the discovery of the brain鈥檚 unique waste removal system and its role in a number of neurological disorders. Nedergaard maintains labs at the Medical Center and the University of Copenhagen.
In 2012, was the first to reveal the brain鈥檚 unique process of removing waste, dubbed the glymphatic system, which consists of a plumbing system that piggybacks on the brain鈥檚 blood vessels and pumps cerebral spinal fluid (CSF) through the brain鈥檚 tissue, flushing away waste.
Nedergaard鈥檚 lab has since gone on to show that the glymphatic system:
- ,
- could be a聽,
- 颈蝉听,
- may be聽, and
- could be harnessed as a new way to聽.
