Montanino Annaclaudia, Saeedimasine Marzieh, Villa Alessandra, Kleiven Svein
Division of Neuronic Engineering, Royal Institute of Technology (KTH), Huddinge SE-14152, Sweden.
Department of Biosciences and Nutrition, Karolinska Institutet (KI), Huddinge SE-14152, Sweden.
J Biomech Eng. 2019 Dec 1;141(12). doi: 10.1115/1.4044953.
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.
弥漫性轴索损伤（DAI）是创伤性脑损伤（TBI）的病理后果，为了首先理解并进而可能预防这种损伤，最需要采用多尺度方法。实际上，机械性损伤通常发生在头部（或宏观）层面，但其后果却影响细胞（或微观）层面的结构。迄今为止，对轴索损伤耐受性的探索已通过实验和计算方法进行。一方面，实验方法在施加机械负荷后识别明确的轴索损伤触发因素时面临与时间和空间分辨率相关的挑战。另一方面，计算方法通常将轴突视为同质实体，因此无法推断其生存能力，而轴突的生存能力被认为取决于亚细胞损伤。在此，我们提出一种计算多尺度方法，以研究两种典型实验场景下轴索损伤的起始情况。我们分别使用复合有限元轴突模型模拟了单细胞和组织拉伸损伤，该模型分别单独存在和嵌入基质中。对轴索损伤的推断基于轴膜应变与先前确定的机械穿孔阈值之间的比较。我们的结果表明，在发生机械穿孔之前，嵌入组织中的轴突比孤立的轴突能够承受更高的变形，并且应变率从1/s增加到10/s会加剧这种情况。
