Repetitive Blast Promotes Chronic Aversion to Neutral Cues Encountered in the Peri-Blast Environment.
Repetitive Blast Promotes Chronic Aversion to Neutral Cues Encountered in the Peri-Blast Environment.
复制标题
重复的爆炸会促进对爆炸周围环境中遇到的中性线索的长期厌恶。
DOI：
10.1089/neu.2020.7061
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发表时间：
2021
影响因子：
4.2
通讯作者：
Cook,DavidG
中科院分区：
文献类型：
--
作者：
Schindler,AbigailG;Terry,GarthE;Wolden-Hanson,Tami;Cline,Marcella;Park,Michael;Lee,Janet;Yagi,Mayumi;Meabon,JamesS;Peskind,ElaineR;Raskind,MurrayM;Phillips,PaulEM;Cook,DavidG
重复性轻度创伤性脑损伤（mTBI）被称为伊拉克和阿富汗战争中军人的“标志性损伤”，并且与创伤后应激障碍（PTSD）高度共病。对不良冲击波诱发的mTBI和/或PTSD的正确归因仍然具有挑战性。使用动物模型的临床前研究可以为爆炸产生损伤和功能障碍的机制提供重要的见解，但仅限于这些模型反映人类经历的程度。避免创伤提醒是PTSD的一个标志。在这里，我们试图了解除了爆炸引起的身体伤害之外，爆炸的小鼠模型是否再现了这种现象。从慢性应激和巴甫洛夫条件反射文献的成熟的工作，我们假设，即使一个是在爆炸暴露麻醉，在爆炸周围环境中遇到的环境线索可以条件反射，以唤起厌恶/烦躁不安和创伤性应激的重新体验。使用气动冲击管，概括战场相关的露天爆炸力，我们提供了直接的证据表明，压力是固有的重复爆炸暴露，导致慢性厌恶/dysphoric样反应，以前的爆炸配对线索。本报告中的结果表明，尽管单次和重复爆炸暴露都会产生急性应激反应（体重减轻，皮质酮增加），但只有重复爆炸暴露才会导致共同发生的厌恶/抑郁样应激反应。这些结果扩展了对重复爆炸暴露的高度复杂性的认识;并进一步支持了目前多个实验室使用的动物建模方法的潜在翻译相关性，这些方法旨在阐明重复爆炸暴露的机制（分子和行为）。
Repetitive mild traumatic brain injury (mTBI) has been called the “signature injury” of military service members in the Iraq and Afghanistan wars and is highly comorbid with post-traumatic stress disorder (PTSD). Correct attribution of adverse blast-induced mTBI and/or PTSD remains challenging. Pre-clinical research using animal models can provide important insight into the mechanisms by which blast produces injury and dysfunction—but only to the degree by which such models reflect the human experience. Avoidance of trauma reminders is a hallmark of PTSD. Here, we sought to understand whether a mouse model of blast reproduces this phenomenon, in addition to blast-induced physical injuries. Drawing on well-established work from the chronic stress and Pavlovian conditioning literature, we hypothesized that even while one is anesthetized during blast exposure, environmental cues encountered in the peri-blast environment could be conditioned to evoke aversion/dysphoria and re-experiencing of traumatic stress. Using a pneumatic shock tube that recapitulates battlefield-relevant open-field blast forces, we provide direct evidence that stress is inherent to repetitive blast exposure, resulting in chronic aversive/dysphoric-like responses to previous blast-paired cues. The results in this report demonstrate that, although both single and repetitive blast exposures produce acute stress responses (weight loss, corticosterone increase), only repetitive blast exposure also results in co-occurring aversive/dysphoric-like stress responses. These results extend appreciation of the highly complex nature of repetitive blast exposure; and lend further support for the potential translational relevance of animal modeling approaches currently used by multiple laboratories aimed at elucidating the mechanisms (both molecular and behavioral) of repetitive blast exposure.