Computational and In Vitro Studies of Blast-Induced Blood-Brain Barrier Disruption

Abstract

There is growing concern that blast-exposed individuals are at risk of developing neurological disorders later in life. Therefore, it is important to understand the dynamic properties of blast forces on brain cells, including the endothelial cells that maintain the blood-brain barrier (BBB), which regulates the passage of nutrients into the brain and protects it from toxins in the blood. To better understand the effect of shock waves on the BBB we have investigated an {\em in vitro} model in which BBB endothelial cells are grown in transwell vessels and exposed in a shock tube, confirming that BBB integrity is directly related to shock wave intensity. It is difficult to directly measure the forces acting on these cells in the transwell container during the experiments, and so a computational tool has been developed and presented in this paper. Two-dimensional axisymmetric Euler equations with the Tammann equation of state were used to model the transwell materials, and a high-resolution finite volume method based on Riemann solvers and the Clawpack software was used to solve these equations in a mixed Eulerian/Lagrangian frame. Results indicated that the geometry of the transwell plays a significant role in the observed pressure time series in these experiments. We also found that pressures can fall below vapor pressure due to the interaction of reflecting and diffracting shock waves, suggesting that cavitation bubbles could be a damage mechanism. Computations that include a simulated hydrophone inserted in the transwell suggest that the instrument itself could significantly alter blast wave properties. These findings illustrate the need for further computational modeling studies aimed at understanding possible blast-induced BBB damage.