Rostami Elham, Davidsson Johan, Ng Kian Chye, Lu Jia, Gyorgy Andrea, Walker John, Wingo Daniel, Plantman Stefan, Bellander Bo-Michael, Agoston Denes V, Risling Mårten
Department of Neuroscience, Karolinska Institutet Stockholm, Sweden.
Front Neurol. 2012 Jul 23;3:115. doi: 10.3389/fneur.2012.00115. eCollection 2012.
Mild traumatic brain injury (mTBI) is one of the most common neuronal insults and can lead to long-term disabilities. mTBI occurs when the head is exposed to a rapid acceleration-deceleration movement triggering axonal injuries. Our limited understanding of the underlying pathological changes makes it difficult to predict the outcome of mTBI. In this study we used a scalable rat model for rotational acceleration TBI, previously characterized for the threshold of axonal pathology. We have analyzed whether a TBI just above the defined threshold would induce any detectable behavioral changes and/or changes in serum biomarkers. The effect of injury on sensory motor functions, memory and anxiety were assessed by beam walking, radial arms maze and elevated plus maze at 3-7 days following TBI. The only behavioral deficits found were transient impairments in working and reference memory. Blood serum was analyzed at 1, 3, and 14 days after injury for changes in selected protein biomarkers. Serum levels of neurofilament heavy chain and Tau, as well as S100B and myelin basic protein showed significant increases in the injured animals at all time points. No signs of macroscopic injuries such as intracerebral hematomas or contusions were found. Amyloid precursor protein immunostaining indicated axonal injuries at all time points analyzed. In summary, this model mimics some of the key symptoms of mTBI, such as transient memory impairment, which is paralleled by an increase in serum biomarkers. Our findings suggest that serum biomarkers may be used to detect mTBI. The model provides a suitable foundation for further investigation of the underlying pathology of mTBI.
轻度创伤性脑损伤（mTBI）是最常见的神经元损伤之一，可导致长期残疾。当头部受到快速加速 - 减速运动，引发轴突损伤时，就会发生mTBI。我们对其潜在病理变化的了解有限，这使得预测mTBI的结果变得困难。在本研究中，我们使用了一种可扩展的大鼠旋转加速性脑损伤模型，该模型先前已确定轴突病理学阈值。我们分析了刚好高于定义阈值的脑损伤是否会引起任何可检测到的行为变化和/或血清生物标志物的变化。在脑损伤后3 - 7天，通过横梁行走、放射状臂迷宫和高架十字迷宫评估损伤对感觉运动功能、记忆和焦虑的影响。发现的唯一行为缺陷是工作记忆和参考记忆的短暂受损。在损伤后1天、3天和14天分析血清，以检测选定蛋白质生物标志物的变化。在所有时间点，受伤动物的血清神经丝重链、Tau以及S100B和髓鞘碱性蛋白水平均显著升高。未发现脑内血肿或挫伤等宏观损伤迹象。淀粉样前体蛋白免疫染色表明在所有分析时间点均存在轴突损伤。总之，该模型模拟了mTBI的一些关键症状，如短暂性记忆障碍，同时血清生物标志物也会升高。我们的研究结果表明，血清生物标志物可用于检测mTBI。该模型为进一步研究mTBI的潜在病理学提供了合适的基础。
