Axons Embedded in a Tissue May Withstand Larger Deformations Than Isolated Axons Before Mechanoporation Occurs.

Diffuse axonal injury (DAI) is the pathological consequence of traumatic brain injury (TBI) that most of all requires a multiscale approach in order to be, first, understood and then possibly prevented. While in fact the mechanical insult usually happens at the head (or macro) level, the consequences affect structures at the cellular (or microlevel). The quest for axonal injury tolerances has so far been addressed both with experimental and computational approaches. On one hand, the experimental approach presents challenges connected to both temporal and spatial resolution in the identification of a clear axonal injury trigger after the application of a mechanical load. On the other hand, computational approaches usually consider axons as homogeneous entities and therefore are unable to make inferences about their viability, which is thought to depend on subcellular damages. Here, we propose a computational multiscale approach to investigate the onset of axonal injury in two typical experimental scenarios. We simulated single-cell and tissue stretch injury using a composite finite element axonal model in isolation and embedded in a matrix, respectively. Inferences on axonal damage are based on the comparison between axolemma strains and previously established mechanoporation thresholds. Our results show that, axons embedded in a tissue could withstand higher deformations than isolated axons before mechanoporation occurred and this is exacerbated by the increase in strain rate from 1/s to 10/s.