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创伤性脑损伤大型动物加速模型中头部运动学的可重复性与特征分析

Reproducibility and Characterization of Head Kinematics During a Large Animal Acceleration Model of Traumatic Brain Injury.

作者信息

Mayer Andrew R, Ling Josef M, Dodd Andrew B, Rannou-Latella Julie G, Stephenson David D, Dodd Rebecca J, Mehos Carissa J, Patton Declan A, Cullen D Kacy, Johnson Victoria E, Pabbathi Reddy Sharvani, Robertson-Benta Cidney R, Gigliotti Andrew P, Meier Timothy B, Vermillion Meghan S, Smith Douglas H, Kinsler Rachel

机构信息

The Mind Research Network/Lovelace Biomedical Research Institute, Albuquerque, NM, United States.

Neurology Department, University of New Mexico School of Medicine, Albuquerque, NM, United States.

出版信息

Front Neurol. 2021 Jun 9;12:658461. doi: 10.3389/fneur.2021.658461. eCollection 2021.

Abstract

Acceleration parameters have been utilized for the last six decades to investigate pathology in both human and animal models of traumatic brain injury (TBI), design safety equipment, and develop injury thresholds. Previous large animal models have quantified acceleration from impulsive loading forces (i.e., machine/object kinematics) rather than directly measuring head kinematics. No study has evaluated the reproducibility of head kinematics in large animal models. Nine (five males) sexually mature Yucatan swine were exposed to head rotation at a targeted peak angular velocity of 250 rad/s in the coronal plane. The results indicated that the measured peak angular velocity of the skull was 51% of the impulsive load, was experienced over 91% longer duration, and was multi- rather than uni-planar. These findings were replicated in a second experiment with a smaller cohort ( = 4). The reproducibility of skull kinematics data was mostly within acceptable ranges based on published industry standards, although the coefficients of variation (8.9% for peak angular velocity or 12.3% for duration) were higher than the impulsive loading parameters produced by the machine (1.1 vs. 2.5%, respectively). Immunohistochemical markers of diffuse axonal injury and blood-brain barrier breach were not associated with variation in either skull or machine kinematics, suggesting that the observed levels of variance in skull kinematics may not be biologically meaningful with the current sample sizes. The findings highlight the reproducibility of a large animal acceleration model of TBI and the importance of direct measurements of skull kinematics to determine the magnitude of angular velocity, refine injury criteria, and determine critical thresholds.

摘要

在过去的六十年里,加速度参数一直被用于研究创伤性脑损伤(TBI)的人类和动物模型中的病理学、设计安全设备以及确定损伤阈值。以往的大型动物模型通过脉冲加载力(即机器/物体运动学)来量化加速度,而非直接测量头部运动学。尚无研究评估大型动物模型中头部运动学的可重复性。九只(五只雄性)性成熟的尤卡坦猪在冠状面以250 rad/s的目标峰值角速度进行头部旋转。结果表明,颅骨的测量峰值角速度为脉冲负荷的51%,持续时间长91%以上,且为多平面而非单平面。这些发现在第二个较小样本量(n = 4)的实验中得到了重复。根据已发表的行业标准,颅骨运动学数据的可重复性大多在可接受范围内,尽管变异系数(峰值角速度为8.9%,持续时间为12.3%)高于机器产生的脉冲负荷参数(分别为1.1%和2.5%)。弥漫性轴索损伤和血脑屏障破坏的免疫组化标记与颅骨或机器运动学的变化均无关联,这表明在当前样本量下,颅骨运动学中观察到的变异水平可能在生物学上并无意义。这些发现突出了TBI大型动物加速度模型的可重复性以及直接测量颅骨运动学对于确定角速度大小、完善损伤标准和确定临界阈值的重要性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/45e0/8219951/cc39ff13213a/fneur-12-658461-g0001.jpg

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