Modeling Neuro-Inflammatory Blood-Brain Barrier Dysfunction: A Computational Analysis of Molecular Diffusion

Overview

The blood–brain barrier (BBB) is a selective physiological barrier that regulates the movement of molecules between the bloodstream and the central nervous system. In neuroinflammatory conditions such as Multiple Sclerosis, BBB permeability is altered, which can significantly impact molecular transport into the brain. The purpose of this project was to develop a computational model to analyze how changes in BBB permeability affect molecular diffusion and to evaluate how modifying molecular properties may improve transport. My model was constructed based on principles of Fick’s First Law of Diffusion, where diffusion was calculated as a function of permeability and molecular weight. Three molecules: glycine, caffeine, and propranolol were analyzed under simulated healthy, mild, and severe neuroinflammatory conditions. For each condition, three trials were conducted with slight variability in permeability (±2%) to simulate biological variation, and average diffusion scores were calculated. Additionally, the model was extended to include lipophilicity (LogP) as a variable, and a 10% increase in lipophilicity was applied to a model compound to evaluate its effect on diffusion while maintaining biologically relevant constraints. Results indicated that increased BBB permeability led to higher diffusion scores across all molecules, with smaller molecules demonstrating greater overall transport. The addition of lipophilicity further enhanced predicted diffusion, supporting its role in membrane permeability. These findings suggest that both barrier conditions and molecular properties significantly influence transport across the BBB. My study demonstrates that computational modeling can be used to simulate BBB dysfunction and predict molecular behavior under neuroinflammatory conditions. My model also provides a framework for exploring strategies to optimize drug delivery to the brain in diseases such as Multiple Sclerosis.