Turner Ryan C, VanGilder Reyna L, Naser Zachary J, Lucke-Wold Brandon P, Bailes Julian E, Matsumoto Rae R, Huber Jason D, Rosen Charles L
*Department of Neurosurgery, West Virginia University School of Medicine, Morgantown, West Virginia; ‡The Center for Neuroscience, West Virginia University School of Medicine, Morgantown, West Virginia; §Department of Nursing, West Virginia University School of Medicine, Morgantown, West Virginia; ‖Department of Neurosurgery, NorthShore University Health System, University of Chicago Pritzker School of Medicine, Evanston, Illinois; ¶Department of Basic Pharmaceutical Sciences, West Virginia University School of Pharmacy, Morgantown, West Virginia.
Neurosurgery. 2014 Apr;74(4):382-94; discussion 394. doi: 10.1227/NEU.0000000000000292.
Concussion remains a symptom-based diagnosis clinically, yet preclinical studies investigating traumatic brain injury, of which concussion is believed to represent a "mild" form, emphasize histological end points with functional assessments often minimized or ignored all together. Recently, clinical studies have identified the importance of cognitive and neuropsychiatric symptoms, in addition to somatic concerns, following concussion. How these findings may translate to preclinical studies is unclear at present.
To address the contrasting end points used clinically compared with those in preclinical studies and the potential role of functional assessments in a commonly used model of diffuse axonal injury (DAI).
Animals were subjected to DAI by the use of the impact-acceleration model. Functional and behavioral assessments were conducted during 1 week following DAI before the completion of the histological assessment at 1 week post-DAI.
We show, despite the suggestion that this model represents concussive injury, no functional impairments as determined by using the common measures of motor, sensorimotor, cognitive, and neuropsychiatric function following injury over the course of 1 week. The lack of functional deficits is in sharp contrast to neuropathological findings indicating neural degeneration, astrocyte reactivity, and microglial activation.
Future studies are needed to identify functional assessments, neurophysiologic techniques, and imaging assessments more apt to distinguish differences following so-called "mild" traumatic brain injury in preclinical models and determine whether these models are truly studying concussive or subconcussive injury. These studies are needed not only to understand the mechanism of injury and production of subsequent deficits, but also to rigorously evaluate potential therapeutic agents.
在临床上，脑震荡仍然是基于症状的诊断，然而，在研究创伤性脑损伤的临床前研究中（脑震荡被认为是其“轻度”形式），重点是组织学终点，而功能评估往往被最小化或完全忽略。最近，临床研究已经确定了脑震荡后除躯体问题外认知和神经精神症状的重要性。目前尚不清楚这些发现如何转化为临床前研究。
解决临床使用的终点与临床前研究中使用的终点之间的差异，以及功能评估在常用的弥漫性轴索损伤（DAI）模型中的潜在作用。
使用撞击-加速模型使动物遭受弥漫性轴索损伤。在弥漫性轴索损伤后第1周完成组织学评估之前，于损伤后1周内进行功能和行为评估。
我们发现，尽管有人认为该模型代表脑震荡损伤，但在损伤后的1周内，通过常用的运动、感觉运动、认知和神经精神功能测量方法，未发现功能受损。功能缺陷的缺乏与神经病理学结果形成鲜明对比，后者显示神经变性、星形胶质细胞反应性和小胶质细胞活化。
未来的研究需要确定更适合区分临床前模型中所谓“轻度”创伤性脑损伤后差异的功能评估、神经生理学技术和影像学评估，并确定这些模型是否真的在研究脑震荡或亚脑震荡损伤。这些研究不仅需要了解损伤机制和随后缺陷的产生，还需要严格评估潜在的治疗药物。
