Modeling interstitial flow physics in the porous brain cortex

Interstitial fluid in the spaces between cells in the brain cortex can be driven by ionic waves that induce cell swelling, although the precise flow physics is not understood. Modeling interstitial fluid dynamics is crucial because of its essential role in brain health and neurological disorders. The brain tissue can be considered a porous medium consisting of a liquid phase and an absorbent solid phase (cells) that can swell. The overall goal of the project is to develop a swelling-porous media model to understand how traveling waves in the brain drive interstitial fluid flow during phases of sleep, during working memory, and during acute conditions like migraine, brain injury, and seizures. The research will advance the fields of porous media flows, biofluid dynamics, and neuroscience. It could drive the development of therapeutic strategies against neurological disorders that are the leading causes of death and disability worldwide. The project’s educational activities include mentoring PhD and undergraduate students, creating a course on “Neuro-fluid Dynamics,” and organizing a workshop for high school students. The project will develop a swelling-porous media model to understand how traveling waves in the brain during acute and physiological conditions drive interstitial fluid flow. The research proposes a rigorous system of volume-averaged conservation equations to model interstitial fluid dynamics in the porous brain cortex. The project will have the following objectives: 1. Model interstitial fluid dynamics by using a volume-averaging technique and deriving a modified Darcy’s law for flows through a porous media with spatiotemporally varying permeability profiles; 2. Quantifying interstitial fluid flow driven by traveling waves by implementing physiological reaction-diffusion equations, traveling wave models, and osmosis-induced porosity fluctuations that will be coupled with the interstitial fluid flow model; and 3. Quantifying the influence of wave properties on interstitial fluid flow by systematically varying the wave properties. Parameter regimes will be identified where interstitial fluid flow is optimized in healthy and diseased brains. The research will constitute the first model of traveling wave-induced interstitial fluid dynamics in the brain cortex and will side-step the experimental bottleneck of visualizing interstitial flow in the cortex. The broader impacts include providing insights into therapeutic strategies against neurological disorders, mentoring graduate and undergraduate students, creating a course on neuro-fluid dynamics, and organizing a workshop for high school students. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.