Center for Brain Injury and Repair, Department of Neurosurgery, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
J Neurotrauma. 2011 Sep;28(9):1747-55. doi: 10.1089/neu.2011.1913. Epub 2011 Sep 6.
Until recently, mild traumatic brain injury (mTBI) or "concussion" was generally ignored as a major health issue. However, emerging evidence suggests that this injury is by no means mild, considering it induces persisting neurocognitive dysfunction in many individuals. Although little is known about the pathophysiological aspects of mTBI, there is growing opinion that diffuse axonal injury (DAI) may play a key role. To explore this possibility, we adapted a model of head rotational acceleration in swine to produce mTBI by scaling the mechanical loading conditions based on available biomechanical data on concussion thresholds in humans. Using these input parameters, head rotational acceleration was induced in either the axial plane (transverse to the brainstem; n=3), causing a 10- to 35-min loss of consciousness, or coronal plane (circumferential to the brainstem; n=2), which did not produce a sustained loss of consciousness. Seven days following injury, immunohistochemical analyses of the brains revealed that both planes of head rotation induced extensive axonal pathology throughout the white matter, characterized as swollen axonal bulbs or varicosities that were immunoreactive for accumulating neurofilament protein. However, the distribution of the axonal pathology was different between planes of head rotation. In particular, more swollen axonal profiles were observed in the brainstems of animals injured in the axial plane, suggesting an anatomic substrate for prolonged loss of consciousness in mTBI. Overall, these data support DAI as an important pathological feature of mTBI, and demonstrate that surprisingly overt axonal pathology may be present, even in cases without a sustained loss of consciousness.
直到最近，轻度创伤性脑损伤（mTBI）或“脑震荡”通常被忽视为一个主要的健康问题。然而，新出现的证据表明，这种损伤绝不是轻微的，因为它会导致许多人持续存在神经认知功能障碍。尽管对 mTBI 的病理生理方面知之甚少，但越来越多的人认为弥漫性轴索损伤（DAI）可能起着关键作用。为了探索这种可能性，我们改编了猪头部旋转加速模型，通过根据人类脑震荡阈值的可用生物力学数据对机械加载条件进行缩放，从而产生 mTBI。使用这些输入参数，头部在轴向平面（与脑干垂直；n=3）或冠状平面（围绕脑干；n=2）旋转，导致 10-35 分钟的意识丧失。7 天受伤后，大脑的免疫组织化学分析显示，头部旋转的两个平面都在白质中引起了广泛的轴突病理学，表现为肿胀的轴突球或对积聚的神经丝蛋白呈免疫反应性的空泡。然而，轴突病理学的分布在头部旋转的平面之间有所不同。特别是，在轴向平面受伤的动物的脑干中观察到更多肿胀的轴突形态，这表明 mTBI 中长时间意识丧失的解剖学基础。总的来说，这些数据支持 DAI 作为 mTBI 的一个重要病理特征，并表明即使在没有持续意识丧失的情况下，也可能存在明显的轴突病理学。
