Yan E B, Johnstone V P A, Alwis D S, Morganti-Kossmann M-C, Rajan R
Department of Physiology, Monash University, Monash, VIC 3800, Australia.
Department of Epidemiology and Preventive Medicine, Monash University and Australian New Zealand Centre of Intensive Care Research, VIC, Australia.
Neuroscience. 2013 Sep 17;248:17-29. doi: 10.1016/j.neuroscience.2013.05.045. Epub 2013 Jun 2.
The velocity of impact between an object and the human head is a critical factor influencing brain injury outcomes but has not been explored in any detail in animal models. Here we provide a comprehensive overview of the interplay between impact velocity and injury severity in a well-established weight-drop impact acceleration (WDIA) model of diffuse brain injury in rodents. We modified the standard WDIA model to produce impact velocities of 5.4, 5.85 and 6.15 m/s while keeping constant the weight and the drop height. Gradations in impact velocity produced progressive degrees of injury severity measured behaviourally, electrophysiologically and anatomically, with the former two methods showing greater sensitivity to changes in impact velocity. There were impact velocity-dependent reductions in sensorimotor performance and in cortical depth-related depression of sensory cortex responses; however axonal injury (demonstrated by immunohistochemistry for β-amyloid precursor protein and neurofilament heavy-chain) was discernible only at the highest impact velocity. We conclude that the WDIA model is capable of producing graded axonal injury in a repeatable manner, and as such will prove useful in the study of the biomechanics, pathophysiology and potential treatment of diffuse axonal injury.
物体与人类头部之间的撞击速度是影响脑损伤结果的关键因素,但在动物模型中尚未得到详细研究。在此,我们全面概述了在一种成熟的啮齿动物弥漫性脑损伤重量下降撞击加速(WDIA)模型中,撞击速度与损伤严重程度之间的相互作用。我们对标准WDIA模型进行了修改,以产生5.4、5.85和6.15米/秒的撞击速度,同时保持重量和下落高度不变。撞击速度的梯度变化产生了行为学、电生理学和解剖学上不同程度的损伤严重程度,前两种方法对撞击速度的变化表现出更高的敏感性。感觉运动性能以及与皮层深度相关的感觉皮层反应抑制存在与撞击速度相关的降低;然而,轴突损伤(通过β-淀粉样前体蛋白和神经丝重链免疫组织化学证实)仅在最高撞击速度下才可辨别。我们得出结论,WDIA模型能够以可重复的方式产生分级轴突损伤,因此将被证明在弥漫性轴突损伤的生物力学、病理生理学及潜在治疗研究中有用。