Fluid flow in the brain: Sorting the good and the bad

It could end up being a very good thing for people with Alzheimer’s Disease that Jennifer Munson and Ian Kimbrough met.

 Ian Kimbrough, an assistant professor in the School of Neuroscience, a part of the College of Science, came to Virginia Tech in 2016. He specializes in research using live in vivo imaging to model neurological diseases, such as brain tumors and Alzheimer’s.

“Glioblastoma, which is what John McCain had, is one of the more deadly diseases,” Kimbrough said. “Like Alzheimer’s disease, with our current standard of care, there’s not much we can do once it’s diagnosed.”

Munson, an associate professor at the Fralin Biomedical Research Institute at VTC, specializes in how the fluid surrounding a tumor moves, particularly brain tumors. She came to Virginia Tech from the University of Virginia two years ago as an associate professor in the Department of Biomedical Engineering and Mechanics in the College of Engineering, and moved her laboratory to Roanoke this summer.

 “In brain cancer,” Munson explained, “that fluid flow is increased, and that increased flow can drive tumor cells to move away from the tumor.”

Those cells then form “satellite tumors,” making it nearly impossible for a surgeon to remove all the cancerous cells.

In a person with Alzheimer’s, instead of fluid flow increasing, it decreases – and scientists believe that certain proteins that cause Alzheimer’s disease accumulate instead of being carried away by the fluid.

Earlier this year, the National Cancer Institute, part of the National Institutes of Health, extended a grant awarded to Munson for research on “Interstitial fluid flow in Alzheimer’s Disease Progression” and funded the research with an additional $250,000. Munson is the principal investigator, teaming with Kimbrough and Michelle Olsen, associate professor and director of graduate studies in the School of Neuroscience.

At the confluence of the work that Kimbrough was doing independently, and the research Munson was doing independently, is where life-changing discovery could occur.

Before becoming a neuroscientist, Kimbrough specialized in digital media design. He has now combined the two specialties. He uses laser scanning microscopes and has developed novel imaging techniques to study brain diseases.

“Ian does beautiful imaging,” Munson said, “so when I moved here it was a way to look at all the work in a new way and see things we hadn’t seen before.”

“Jennifer’s group has done some excellent work looking at how interstitial fluid flow in the brain affects cancer cell invasion and overall disease progression," Kimbrough said. “It’s not something other people are looking at.”

Munson said that when she arrived at Virginia Tech, she was ready to start new collaborations. It didn’t take her long to find out who her research group could team up with.

“Ian had observed things one way, and I had observed things another way,” Munson said. “Then we both got to the same inherent question.”

The NIH grant will allow their research to start with what Munson’s team and others have learned about the increased fluid flow in brain cancer, and trying to figure out what happens when the opposite occurs with Alzheimer’s disease.

The standard view that “there’s just this junk that builds up” – the accumulated proteins – because of decreased fluid flow in the brain of a person with Alzheimer’s may not be the whole story, Kimbrough said.

Kimbrough’s research has shown that Amyloid beta, the protein that accumulates in the brains of people with Alzheimer’s disease, forms on blood vessels in the brain. The proteins form a “rigid cast” around the blood vessel, he explained, clamping his right fist over his left index finger to show how a blood vessel would be restricted.

“When we think,” Kimbrough said, “neurons require more energy and nearby blood vessels expand to get more blood to that area, but not if those blood vessels are no longer able to dilate.”

Munson and Kimbrough are exploring how specific cells are "activated" by mechanoreceptors that detect changes in the fluid flow around them and how this activation could lead to cellular changes that contribute to disease progression. Munson has published research about a drug-delivery system that can manipulate one of the routes that fluid uses to exit the brain. If successful, the drug could increase fluid flow to drive the built-up proteins out of the brain.

Their goal is to develop the work in this grant into a longer-term research program to develop a better drug-delivery system to target the mechano-receptors.

If it works, progression of Alzheimer’s could be stopped, possibly even reversed, she said.

“Our goal is to launch an entirely new area of research,” Munson said.

“This collaboration,” Kimbrough said, “is just the tip of the iceberg.”