Energy based mechano-electrophysiological model of CNS damage at the tissue scale

Injuries to the central nervous system (CNS) have become a major health challenge in our society. Such injuries can affect the electrophysiological properties, and thus functional behaviour of the nervous system. Most of the related computational studies to date have mainly been focussed on the cellular, subcellular or axonal scales. Although essential for understanding the characteristics of spinal cord injury and traumatic brain injury at the cellular level, these approaches suffer from a lack of scalability to meso- and macroscopic scenarios. To this end, this work presents a tissue level framework describing the coupled mechanical and electrophysiological behaviour of CNS tissue. The proposed mechanical large deformation constitutive model accounts for strain rate dependency, viscous effects and mechanical damage within a thermodynamically consistent framework. Coupled to it, a FitzHugh–Nagumo based model that includes axonal fibre informed anisotropic conduction describes the electrophysiological behaviour. The mechanical model is first calibrated against experimental deformation measurements of spinal cord white matter. The complete framework is then calibrated and used to study the mechano-electrophysiological coupling in spinal cord samples subjected to tension-free relaxation tests by considering electrophysiological damage as a function of mechanical energetic terms. The flexibility of the proposed model is illustrated with the case of mechano-electrophysiological coupling in spinal cord subjected to blast loading. After validation of the coupled model, the mechanical parameters are identified for white matter and an analysis of the influence of axonal dispersion on anisotropic AP conduction in an in silico rat model is presented. This work provides a novel mechano-electrophysiological framework able to model the mechanics of spinal cord and brain tissue and its translation into electrophysiological dysfunction through energetic terms at the tissue level.