Neural activity induces strongly coupled electro-chemo-mechanical interactions and fluid flow in astrocyte networks and extracellular space-A computational study.

The complex interplay between chemical, electrical, and mechanical factors is fundamental to the function and homeostasis of the brain, but the effect of electrochemical gradients on brain interstitial fluid flow, solute transport, and clearance remains poorly quantified. Here, via in-silico experiments based on biophysical modeling, we estimate water movement across astrocyte cell membranes, within astrocyte networks, and within the extracellular space (ECS) induced by neuronal activity, and quantify the relative role of different forces (osmotic, hydrostatic, and electrical) on transport and fluid flow under such conditions. We find that neuronal activity alone may induce intracellular fluid velocities in astrocyte networks of up to 14μm/min, and fluid velocities in the ECS of similar magnitude.

Validating a Computational Framework for Ionic Electrodiffusion with Cortical Spreading Depression as a Case Study.

Cortical spreading depression (CSD) is a wave of pronounced depolarization of brain tissue accompanied by substantial shifts in ionic concentrations and cellular swelling. Here, we validate a computational framework for modeling electrical potentials, ionic movement, and cellular swelling in brain tissue during CSD. We consider different model variations representing wild-type (WT) or knock-out/knock-down mice and systematically compare the numerical results with reports from a selection of experimental studies.

Accurate numerical simulation of electrodiffusion and water movement in brain tissue.

Mathematical modelling of ionic electrodiffusion and water movement is emerging as a powerful avenue of investigation to provide a new physiological insight into brain homeostasis. However, in order to provide solid answers and resolve controversies, the accuracy of the predictions is essential. Ionic electrodiffusion models typically comprise non-trivial systems of non-linear and highly coupled partial and ordinary differential equations that govern phenomena on disparate time scales.

Parametric exploration of cellular swelling in a computational model of cortical spreading depression.

Cortical spreading depression (CSD) is a slowly propagating wave of depolarization of brain cells, followed by temporary silenced electrical brain activity. Major structural changes during CSD are linked to neuronal and possibly glial swelling. However, basic questions still remain unanswered.

Finite Element Simulation of Ionic Electrodiffusion in Cellular Geometries.

Mathematical models for excitable cells are commonly based on cable theory, which considers a homogenized domain and spatially constant ionic concentrations. Although such models provide valuable insight, the effect of altered ion concentrations or detailed cell morphology on the electrical potentials cannot be captured. In this paper, we discuss an alternative approach to detailed modeling of electrodiffusion in neural tissue.