Utilizing a Structural Mechanics Approach to Assess the Primary Effects of Injury Loads Onto the Axon and Its Components

Diffuse axonal injury (DAI) occurs as a result of the transmission of rapid dynamic loads from the head to the brain and specifically to its neurons. Despite being one of the most common and most deleterious types of traumatic brain injury (TBI), the inherent cell injury mechanism is yet to be understood. Experimental observations have led to the formulation of different hypotheses, such as mechanoporation of the axolemma and microtubules (MTs) breakage. With the goal of singling out the mechanical aspect of DAI and to resolve the ambiguity behind its injury mechanism, a composite finite element (FE) model of a representative volume of an axon was developed. Once calibrated and validated against published experimental data, the axonal model was used to simulate injury scenarios. The resulting strain distributions along its components were then studied in dependence of strain rate and of typical modeling choices such as the applied MT constraints and tau proteins failure. Results show that oversimplifying the MT bundle kinematic entails a systematic attenuation ( = 2.33) of the computed maximum MT strain. Nevertheless, altogether, results support the hypothesis of axolemma mechanoporation as a cell-injury trigger. Moreover, for the first time the interconnection between the axolemma and the MT bundle is shown to play a role in damage localization. The proposed FE axonal model is a valuable tool to understand the axonal injury mechanism from a mechanical perspective and could be used in turn for the definition of well-informed injury criteria at the tissue and organ level.