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With the growing body of research on traumatic brain injury and spinal cord injury, computational neuroscience has recently focused its modeling efforts on neuronal functional deficits following mechanical loading. However, in most of these efforts, cell damage is generally only characterized by purely mechanistic criteria, functions of quantities such as stress, strain or their corresponding rates. The modeling of functional deficits in neurites as a consequence of macroscopic mechanical insults has been rarely explored. In particular, a quantitative mechanically based model of electrophysiological impairment in neuronal cells, Neurite, has only very recently been proposed. In this paper, we present the implementation details of this model: a finite difference parallel program for simulating electrical signal propagation along neurites under mechanical loading. Following the application of a macroscopic strain at a given strain rate produced by a mechanical insult, Neurite is able to simulate the resulting neuronal electrical signal propagation, and thus the corresponding functional deficits. The simulation of the coupled mechanical and electrophysiological behaviors requires computational expensive calculations that increase in complexity as the network of the simulated cells grows. The solvers implemented in Neurite—explicit and implicit—were therefore parallelized using graphics processing units in order to reduce the burden of the simulation costs of large scale scenarios. Cable Theory and Hodgkin-Huxley models were implemented to account for the electrophysiological passive and active regions of a neurite, respectively, whereas a coupled mechanical model accounting for the neurite mechanical behavior within its surrounding medium was adopted as a link between electrophysiology and mechanics. This paper provides the details of the parallel implementation of Neurite, along with three different application examples: a long myelinated axon, a segmented dendritic tree, and a damaged axon. The capabilities of the program to deal with large scale scenarios, segmented neuronal structures, and functional deficits under mechanical loading are specifically highlighted. [ABSTRACT FROM AUTHOR]

Traumatic brain injury and spinal cord injury have recently been put under the spotlight as major causes of death and disability in the developed world. Despite the important ongoing experimental and modeling campaigns aimed at understanding the mechanics of tissue and cell damage typically observed in such events, the differentiated roles of strain, stress and their corresponding loading rates on the damage level itself remain unclear. More specifically, the direct relations between brain and spinal cord tissue or cell damage, and electrophysiological functions are still to be unraveled. Whereas mechanical modeling efforts are focusing mainly on stress distribution and mechanistic-based damage criteria, simulated function-based damage criteria are still missing. Here, we propose a new multiscale model of myelinated axon associating electrophysiological impairment to structural damage as a function of strain and strain rate. This multiscale approach provides a new framework for damage evaluation directly relating neuron mechanics and electrophysiological properties, thus providing a link between mechanical trauma and subsequent functional deficits. [ABSTRACT FROM AUTHOR]

Abstract Traumatic injuries to the central nervous system (brain and spinal cord) have recently been put under the spotlight because of their devastating socio-economical cost. At the cellular scale, recent research efforts have focussed on primary injuries by making use of models aimed at simulating mechanical deformation induced axonal electrophysiological deficits. The overwhelming majority of these models only consider axonal stretching as a loading mode, while other modes of deformation such as crushing or mixed modes – highly relevant in spinal cord injury – are left unmodelled. To this end, we propose here a novel 3D finite element framework coupling mechanics and electrophysiology by considering the electrophysiological Hodgkin–Huxley and Cable Theory models as surface boundary conditions introduced directly in the weak form, hence eliminating the need to geometrically account for the membrane in its electrophysiological contribution. After validation against numerical and experimental results, the approach is leveraged to model an idealised axonal dislocation injury. The results show that the sole consideration of induced longitudinal stretch following transverse loading of a node of Ranvier is not necessarily enough to capture the extent of axonal electrophysiological deficit and that the non-axisymmetric loading of the node participates to a larger extent to the subsequent damage. On the contrary, a similar transverse loading of internodal regions was not shown to significantly worsen with the additional consideration of the non-axisymmetric loading mode. Highlights • A novel FE framework for 3D mechanical–electrophysiological coupling in axonal membrane is proposed. • The HH and CT equations are considered in the weak form as boundary conditions. • The model is validated against numerical and experimental work. • This framework captures complex injury loading conditions not available to 1D models. [ABSTRACT FROM AUTHOR]