Astrocytic Ion Dynamics: Implications for Potassium Buffering and Liquid Flow

We review modeling of astrocyte ion dynamics with a specific focus on the implications of so-called spatial potassium buffering, where excess potassium in the extracellular space (ECS) is transported away to prevent pathological neural spiking. The recently introduced Kirchoff-Nernst-Planck (KNP) scheme for modeling ion dynamics in astrocytes (and brain tissue in general) is outlined and used to study such spatial buffering. We next describe how the ion dynamics of astrocytes may regulate microscopic liquid flow by osmotic effects and how such microscopic flow can be linked to whole-brain macroscopic flow. We thus include the key elements in a putative multiscale theory with astrocytes linking neural activity on a microscopic scale to macroscopic fluid flow.Comment: 27 pages, 7 figure

Modeling concentration distribution and deformation during convection-enhanced drug delivery into brain tissue

Convection-enhanced drug delivery is a technique where a therapeutic agent is infused under positive pressure directly into the brain tissue. For predicting the final concentration distribution and optimizing infusion rate and catheter placement, numerical models can be of great help. However, despite advances in modeling this process, often the infused agent does not reach the targeted region prescribed in the modeling phase. In this study, patient-specific brain structure and parameters, obtained from diffusion tensor imaging (DTI), are implemented in a numerical model which describes the flow and transport in an elastic deformable matrix. To our knowledge, this is the first time that information from DTI is used in a numerical model which includes both transport of a therapeutic agent and tissue deformation. Fractional anisotropy (FA) is used to distinguish between gray and white matter and tortuosity to differentiate between inside and outside the brain tissue. One voxel in the DT-image is represented by one element of the numerical grid. The DT-images were in addition used to determine the orientation of the white matter fiber tracts and calibrate permeability and diffusion coefficients found in the literature. Values chosen for the porosity and Lamé parameters are also based on those found in the literature. Given realistic literature values, the calibration of the permeability and diffusion tensors are shown to be successful. Our result shows that preferential flow occur in direction of the white matter fiber tracts. The current model assumes linear deformation, corresponding to small porosity changes. But, because large porosity changes occur that may adversely affect drug transport, non-linear deformations should be included in the futur

A continuum mechanics model of enzyme-based tissue degradation in cancer therapies

We propose a mathematical model to describe enzyme-based tissue degradation in cancer therapies. The proposed model combines the poroelastic theory of mixtures with the transport of enzymes or drugs in the extracellular space. The effect of the matrix degrading enzymes on the tissue composition and its mechanical response are accounted for. Numerical simulations in 1D, 2D and ax-isymmetric (3D) configurations show how an injection of matrix degrading enzymes alters the porosity of a biological tissue. We eventually exhibit numerically the main consequences of a matrix degrading enzyme pretreatment in the framework of chemotherapy: the removal of the diffusive hindrance to the penetration of therapeutic molecules in tumors and the reduction of interstitial fluid pressure which improves transcapillary transport. Both effects are consistent with previous biological observations