Electrophysiological white matter dysfunction and association with neurobehavioral deficits following low-level primary blast trauma
Electrophysiological white matter dysfunction and association with neurobehavioral deficits following low-level primary blast trauma
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DOI：
10.1016/j.nbd.2012.12.002
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发表时间：
2013-04-01
影响因子：
6.1
通讯作者：
Baker, Andrew J.
中科院分区：
文献类型：
--
作者：
Park, Eugene;Eisen, Rebecca;Baker, Andrew J.
有强有力的证据表明，原发冲击伤会导致大脑的神经病理改变。退伍军人的临床发现表明弥漫性轴突损伤的证据已经得到了许多动物原始爆炸模型的证实。然而，亚临床冲击波(没有明显的外部创伤或肺损伤迹象的冲击波)作为神经症状和神经病理的促成因素的作用尚不清楚。我们小组最近建立了一种低水平原发母细胞的模型，并表征了亚临床波休克暴露后，大脑皮质和海马区白质细胞骨架蛋白的异常表达。在这里，我们检查了亚临床原始细胞的易感性。我们还证明，白质功能障碍与与焦虑和压力相关的神经行为缺陷有关。麻醉的雄性Spraogue-Dawley大鼠(约300g)暴露于一次冲击波(约28kpa)，低于诱发肺创伤所需的阈值。对大鼠进行三项行为结果评估：旋转棒、明/暗箱和旷场焦虑测试。我们用Western blotting检测轴向表达的细胞膜蛋白、NF200和电压门控性钠通道(VGSC)在胼胝体中的表达和降解。采用急性脑片制片的方法，对其进行了诱发复合动作电位的电生理学分析。有证据表明，在损伤后48小时，可在损伤后14天检测到胼胝体中的阿尔法II-幽灵蛋白降解，以及大量神经丝的表达增加。48h后VGSC的表达减少，Ankyrin G与完整的ALL-Spectrin的相互作用也减少。与假手术组相比，冲击波暴露组大鼠旋转棒潜伏期显著缩短(p=0.002)。与假动物相比，爆炸大鼠的焦虑和应激相关行为增加，表现为在野外测试中粪便频率增加(p=0.029)，探索活动减少(p=0.036)。爆炸大鼠的过渡较少，在亮/暗盒子的亮部分花费的时间也较少。电生理记录显示，损伤后14天，无髓纤维比有髓纤维有更多的缺失，表现为CAP幅度反应降低。对刺激距离与诱发反应之间关系的分析表明，在较近的刺激距离下，N1有髓纤维存在潜在的异常。总而言之，我们的结果表明，亚临床冲击波暴露可以导致脑白质的持续性神经变化，与可检测到的神经行为缺陷同时发生。(C)2012 Elsevier Inc.保留所有权利。
There is strong evidence that primary blast injuries can cause neuropathological alterations in the brain. Clinical findings from war veterans indicating evidence of diffuse axonal injury have been corroborated by numerous primary blast models in animals. However, the effect of a subclinical blast (blast with no obvious sign of external trauma or lung injury) as a contributing factor to the neurological symptoms and neuropathology is less clear. Our group recently developed a model of low-level primary blast and characterized aberrant expression of white matter cytoskeletal proteins in the cortex and hippocampus following a subclinical wave shock exposure. Here we examined the susceptibility of the corpus callosum following subclinical blast. We also demonstrate that white matter dysfunction is associated with neurobehavioral deficits associated with anxiety and stress in rats. Anesthetized male Sprague-Dawley rats (similar to 300 g) were exposed to a primary blast (approx. 28 kPa), below the threshold required to induce pulmonary trauma. Rats were evaluated on three behavioral outcome measures; the rotarod, the light/dark box and open field anxiety test. We used Western blotting to examine expression and degradation of axonally expressed cell-spectrin, NF200 and voltage-gated sodium channels (VGSC) in the corpus callosum. Acute slice preparations were used for electrophysiological analysis of evoked compound action potentials (CAPs) in the corpus callosum. There was evidence of alpha II-spectrin degradation in the corpus callosum at 48 h post-injury detectable up to 14 days post-injury, as well as increased heavy neurofilament expression. A reduction in VGSC expression was observed at 48 h post-blast as well as a reduction in the interaction between ankyrin G and intact all-spectrin. Blast exposed rats had significantly lower rotarod latency times relative to sham rats (p = 0.002). Increased anxiety-related and stress-related behavior were observed in blast rats relative to sham animals as indicated by the increased frequency of fecal droppings (p = 0.029) and reduced exploratory activity (p = 0.036) in the open-field test. Blast rats had fewer transitions and time spent in lit sections of the light/dark box. Electrophysiological recordings from the corpus callosum indicated greater deficits in unmyelinated fibers of the corpus callosum relative to myelinated fibers characterized by reduced CAP amplitude response at 14 days post-injury. Analysis of the relationship between stimulation distance to evoked response indicated an underlying abnormality in N1 myelinated fibers at close stimulation distances. Collectively, our results indicate that subclinical blast exposure can result in persistent neurological changes in cerebral white matter occurring in parallel with detectable neurobehavioral deficits. (C) 2012 Elsevier Inc. All rights reserved.