Mechano-chemical modeling of glia initiated secondary injury of neurons under mechanical load

Abstract

Traumatic Brain Injury (TBI) results from an impact or concussion to the head with the injury being specifically characterized through pathological degradation at various biological length scales. Following injury, various mechanical modeling techniques have been proposed in the literature that seek to quantify neuronal-scale to tissue-scale metrics of brain damage. Broadly, the two categories of degradation encompass physiological deterioration of neurons and upregulation of chemical entities such as neurotransmitters which causes initiation of downstream pathophysiological effects. Despite the many contributing pathways, in this work, we delineate and model a potential glia-initiated injury pathway that leads to secondary injury. The goal of this work is to demonstrate a continuum framework which models the multiphysics of mechano-chemical interactions underlying TBI. Using a coupled PDE (partial differential equation) formulation and FEM (finite element method) discretization, the framework highlights evolution of field variables which spatio-temporally resolve mechanical metrics and chemical species across neuronal clusters. The modeling domain encompasses microglia, neurons and the extracellular matrix. The continuum framework used to model the mechano-chemical interactions assumes a three dimensional viscoelastic network to capture the mechanical response underlying proteins constituting the neuron microstructure and advection-diffusion equations modeling spatio-temporal evolution of chemical species. We use this framework to numerically estimate key concentrations of chemical species produced by the strain field. In this work, we identify key biomarkers within the labyrinth of molecular pathways and build a framework that captures the core mechano-chemical interactions. This framework is an attempt to quantify secondary injury and thus assist in developing targeted TBI treatments.