The Spectrum of Neurobehavioral Sequelae after Repetitive Mild Traumatic Brain Injury: A Novel Mouse Model of Chronic Traumatic Encephalopathy
The Spectrum of Neurobehavioral Sequelae after Repetitive Mild Traumatic Brain Injury: A Novel Mouse Model of Chronic Traumatic Encephalopathy
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DOI：
10.1089/neu.2013.3255
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发表时间：
2014-07-01
影响因子：
4.2
通讯作者：
Huang, Jason H.
中科院分区：
文献类型：
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作者：
Petraglia, Anthony L.;Plog, Benjamin A.;Huang, Jason H.
重复性轻度创伤性脑损伤(TBI)的神经后遗症，特别是神经退行性综合征，如慢性创伤性脑病(CTE)，已受到越来越多的关注；然而，目前还没有动物模型能够捕捉到这种现象的行为谱。我们试图建立一种CTE的动物模型。我们的新模型是两种最流行的脑外伤模型的改进和融合，允许对未麻醉的小鼠进行可控的闭合头部撞击。280只12周龄小鼠随机分为对照组、单次轻度脑损伤组和重复脑损伤组。重复性mTBI小鼠连续7天每天接受6次脑震荡冲击。在不同的时间点对行为进行评估。计算神经功能严重程度评分(NSS)，用握力钢丝试验(WGT)检测前庭运动功能。用Morris水迷宫(MWM)评估认知功能，用高架加迷宫评估焦虑/冒险行为，用强迫游泳/悬尾测试评估抑郁行为。1个月后进行睡眠脑电/肌电检查。与对照组相比，两组脑损伤患者的NSS均升高，并随着时间的推移而改善。重复性mTBI小鼠在WGT上表现出一过性前庭运动缺陷。重复性mTBI小鼠在MWM测试中也表现出缺陷。两个mTBI组在2周时都表现出更多的焦虑，但重复的mTBI组小鼠在1个月时表现出更多的冒险行为，并持续到6个月。重复的mTBI小鼠在1个月时表现出抑郁样行为。这两组人都表现出睡眠障碍。我们在一种新的小鼠模型中描述了重复性mTBI的神经学后遗症，该模型类似于临床上观察到的重复性轻度头部损伤患者的几种神经精神行为。
There has been an increased focus on the neurological sequelae of repetitive mild traumatic brain injury (TBI), particularly neurodegenerative syndromes, such as chronic traumatic encephalopathy (CTE); however, no animal model exists that captures the behavioral spectrum of this phenomenon. We sought to develop an animal model of CTE. Our novel model is a modification and fusion of two of the most popular models of TBI and allows for controlled closed-head impacts to unanesthetized mice. Two-hundred and eighty 12-week-old mice were divided into control, single mild TBI (mTBI), and repetitive mTBI groups. Repetitive mTBI mice received six concussive impacts daily for 7 days. Behavior was assessed at various time points. Neurological Severity Score (NSS) was computed and vestibulomotor function tested with the wire grip test (WGT). Cognitive function was assessed with the Morris water maze (MWM), anxiety/risk-taking behavior with the elevated plus maze, and depression-like behavior with the forced swim/tail suspension tests. Sleep electroencephalogram/electromyography studies were performed at 1 month. NSS was elevated, compared to controls, in both TBI groups and improved over time. Repetitive mTBI mice demonstrated transient vestibulomotor deficits on WGT. Repetitive mTBI mice also demonstrated deficits in MWM testing. Both mTBI groups demonstrated increased anxiety at 2 weeks, but repetitive mTBI mice developed increased risk-taking behaviors at 1 month that persist at 6 months. Repetitive mTBI mice exhibit depression-like behavior at 1 month. Both groups demonstrate sleep disturbances. We describe the neurological sequelae of repetitive mTBI in a novel mouse model, which resemble several of the neuropsychiatric behaviors observed clinically in patients sustaining repetitive mild head injury.