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非人灵长类动物单侧颈脊髓挫伤损伤模型的机械设计与分析

Mechanical Design and Analysis of a Unilateral Cervical Spinal Cord Contusion Injury Model in Non-Human Primates.

作者信息

Sparrey Carolyn J, Salegio Ernesto A, Camisa William, Tam Horace, Beattie Michael S, Bresnahan Jacqueline C

机构信息

1 Mechatronic Systems Engineering, Simon Fraser University , Surrey, British Columbia, Canada .

2 International Collaboration on Repair Discoveries (ICORD) , Vancouver, British Columbia, Canada .

出版信息

J Neurotrauma. 2016 Jun 15;33(12):1136-49. doi: 10.1089/neu.2015.3974. Epub 2016 Apr 19.

Abstract

Non-human primate (NHP) models of spinal cord injury better reflect human injury and provide a better foundation to evaluate potential treatments and functional outcomes. We combined finite element (FE) and surrogate models with impact data derived from in vivo experiments to define the impact mechanics needed to generate a moderate severity unilateral cervical contusion injury in NHPs (Macaca mulatta). Three independent variables (impactor displacement, alignment, and pre-load) were examined to determine their effects on tissue level stresses and strains. Mechanical measures of peak force, peak displacement, peak energy, and tissue stiffness were analyzed as potential determinants of injury severity. Data generated from FE simulations predicted a lateral shift of the spinal cord at high levels of compression (>64%) during impact. Submillimeter changes in mediolateral impactor position over the midline increased peak impact forces (>50%). Surrogate cords established a 0.5 N pre-load protocol for positioning the impactor tip onto the dural surface to define a consistent dorsoventral baseline position before impact, which corresponded with cerebrospinal fluid displacement and entrapment of the spinal cord against the vertebral canal. Based on our simulations, impactor alignment and pre-load were strong contributors to the variable mechanical and functional outcomes observed in in vivo experiments. Peak displacement of 4 mm after a 0.5N pre-load aligned 0.5-1.0 mm over the midline should result in a moderate severity injury; however, the observed peak force and calculated peak energy and tissue stiffness are required to properly characterize the severity and variability of in vivo NHP contusion injuries.

摘要

非人类灵长类动物(NHP)脊髓损伤模型能更好地反映人类损伤情况,并为评估潜在治疗方法和功能结果提供更好的基础。我们将有限元(FE)模型和替代模型与来自体内实验的冲击数据相结合,以确定在恒河猴(猕猴)中产生中度严重程度单侧颈椎挫伤所需的冲击力学。研究了三个独立变量(冲击器位移、对准和预载荷),以确定它们对组织水平应力和应变的影响。分析了峰值力、峰值位移、峰值能量和组织刚度的力学测量值,作为损伤严重程度的潜在决定因素。有限元模拟产生的数据预测,在冲击过程中,脊髓在高压缩水平(>64%)时会发生侧向移位。冲击器在中线以上的中外侧位置发生亚毫米级变化会增加峰值冲击力(>50%)。替代脊髓建立了一个0.5N的预载荷方案,用于将冲击器尖端定位到硬脑膜表面,以在冲击前确定一致的背腹基线位置,这与脑脊液移位以及脊髓在椎管内的嵌顿相对应。基于我们的模拟,冲击器对准和预载荷是体内实验中观察到的可变力学和功能结果的重要因素。在0.5N预载荷后4mm的峰值位移,在中线以上对准0.5 - 1.0mm,应会导致中度严重程度的损伤;然而,需要观察到的峰值力以及计算出的峰值能量和组织刚度来正确表征体内NHP挫伤损伤的严重程度和变异性。

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