Blast Wave Exposure Impairs Memory and Decreases Axon Initial Segment Length
Blast Wave Exposure Impairs Memory and Decreases Axon Initial Segment Length
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DOI：
10.1089/neu.2012.2478
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发表时间：
2013-05-01
影响因子：
4.2
通讯作者：
Rasband, Matthew N.
中科院分区：
文献类型：
--
作者：
Baalman, Kelli L.;Cotton, R. James;Rasband, Matthew N.
暴露于冲击波被认为会导致轻度创伤性脑损伤（mTBI），症状包括认知、记忆和行为改变。然而，这一想法仍然存在争议，爆炸引起的脑损伤的机制仍然未知。为了开始解决这些问题，我们建造了一个简单的压缩空气激波管，将大鼠放在管内，并将它们暴露在高度可重复和可控的冲击波中。与轻度损伤的产生一致，暴露于爆炸后2周，我们发现运动表现不受影响，并且一组常见的损伤标记物在皮质、胼胝体或海马体中的表达几乎没有或没有显著变化。同样，我们也无法检测到从爆炸暴露的大鼠大脑中收集的高血影蛋白分解产物。然而，使用物体识别任务，我们发现暴露于冲击波的大鼠与对照组大鼠相比，探索新物体的时间显着减少。有趣的是，我们还观察到爆炸暴露大鼠的皮层和海马中轴突起始段（AIS）显著缩短，表明暴露于爆炸后神经元兴奋性改变。一个计算模型表明，缩短AIS增加了阈值和重复放电神经元的峰间期。这些结果支持以下结论：暴露于单一冲击波可导致mTBI，伴随认知障碍和神经元分子组织的亚细胞变化。
Exposure to a blast wave has been proposed to cause mild traumatic brain injury (mTBI), with symptoms including altered cognition, memory, and behavior. This idea, however, remains controversial, and the mechanisms of blast-induced brain injury remain unknown. To begin to resolve these questions, we constructed a simple compressed air shock tube, placed rats inside the tube, and exposed them to a highly reproducible and controlled blast wave. Consistent with the generation of a mild injury, 2 weeks after exposure to the blast, we found that motor performance was unaffected, and a panel of common injury markers showed little or no significant changes in expression in the cortex, corpus callosum, or hippocampus. Similarly, we were unable to detect elevated spectrin breakdown products in brains collected from blast-exposed rats. Using an object recognition task, however, we found that rats exposed to a blast wave spent significantly less time exploring a novel object when compared with control rats. Intriguingly, we also observed a significant shortening of the axon initial segment (AIS) in both the cortex and hippocampus of blast-exposed rats, suggesting altered neuronal excitability after exposure to a blast. A computational model showed that shortening the AIS increased both threshold and the interspike interval of repetitively firing neurons. These results support the conclusion that exposure to a single blast wave can lead to mTBI with accompanying cognitive impairment and subcellular changes in the molecular organization of neurons.