Interstitial Fluid Flow in the Brain: Contributions to Disease

Jennifer M. Munson, Ph.D.
Assistant Professor in the Department of Biomedical Engineering
Virginia Tech
Bruggeman Room, CBIS, Rensselaer Polytechnic Institute
Thu, December 05, 2019 at 2:30 PM

Fluid flow in the brain is an emerging area of research with implications in Alzheimer’s, aging, brain homeostasis, development, and cancer. In cancers, fluid flow is increased, whereas in cognitive decline, fluid flow decreases. In my laboratory, we study the role of interstitial fluid flow, or the fluid flow within the spaces of tissues, on cellular behaviors. We have developed an array of techniques and tools to measure, model, and manipulate fluid flow in the brain. In glioblastoma, the deadliest form of brain cancer, cellular invasion is a defining factor of its resistance to therapeutic intervention and poor patient prognosis. Invasion in the brain follows distinctive routes that correlate with interstitial and bulk flow pathways. By conducting in vivo measurements of interstitial flow, using MRI techniques, we have identified specific flow velocities and correlated interstitial fluid flow to patterns of tumor invasion, glial activation, extracellular matrix deposition, and receptor activation in tumor-associated brain along these invasive pathways. To examine how interstitial fluid flow interacts with this specific invasive microenvironment,  we have developed tissue engineered models of the brain that recapitulate patient tissue.  We have found that interstitial flow can enhance invasion of brain cancer cells using both cell lines and patient-derived glioma stem cells. These effects are mediated simultaneously by chemical and mechanical mechanisms. Interstitial fluid flow also activates glial cells in the brain tumor microenvironment, initiating chemotactic spread of brain tumor cells. In Alzheimer’s disease, we have seen that alteration of tissue drainage via manipulation of the newly discovered meningeal lymphatics can increase or decrease interstitial fluid flow. These changes have downstream affects that can alter cognitive function in mice, and alter transport of large molecules in the brain. These findings implicate interstitial fluid flow as a driver of brain tissue morphology and indicate multiple mechanisms through which fluid flow can mediate cellular responses. In this talk, I will discuss the nature and implications of interstitial fluid flow in the brain, identifying both tissue-level and cellular-level mechanisms and how our lab uses diverse approaches (in vitro, in vivo, ex vivo, in silico) to study this phenomenon.

Jennifer M Munson, Ph.D.

Dr. Munson is an Assistant Professor in the Department of Biomedical Engineering at Virginia Tech and the Virginia Tech-Wake Forest School of Biomedical Engineering and Sciences and an affiliate member of the Wake Forest Comprehensive Cancer Institute. She received her Ph.D. from Georgia institute of Technology in 2011 and completed her postdoctoral training at the Swiss Federal Institute of Technology in Lausanne (EPFL). During her training, she was supported by the NSFGRFP, a Fulbright Fellowship, and a Whitaker Scholarship. Prior to her appointment at Virginia Tech, Dr. Munson was an Assistant Professor in the Department of Biomedical Engineering at the University of Virginia. Her laboratory studies the role of fluid flow in tissue homeostasis and disease with a specific focus on cancer and neurological disorders. She uses tissue engineered cell culture models, in vivo imaging methodology, and computational modeling to explore the nature and impact of interstitial fluid flow on cells and tissues. Dr. Munson has received funding from the NCI, NIBIB, Coulter Foundation, and the American Cancer Society. In 2016, Dr. Munson was awarded the Rita Schaffer Young Investigator Award from the Biomedical Engineering Society, and in 2017, she was awarded the Cellular and Molecular Bioengineering Young Innovator Award. She also serves as the Department Diversity and Inclusion Chair.