Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, Washington, USA.
Graduate Program in Neuroscience, University of Washington, Seattle, Washington, USA.
J Neurotrauma. 2021 Apr 1;38(7):940-948. doi: 10.1089/neu.2020.7061. Epub 2020 Dec 16.
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.
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。正确归因于不良爆炸引起的 mTBI 和/或 PTSD 仍然具有挑战性。使用动物模型的临床前研究可以为爆炸引起损伤和功能障碍的机制提供重要的见解-但仅限于此类模型反映人类经验的程度。避免创伤提示是 PTSD 的一个标志。在这里，我们试图了解爆炸的小鼠模型是否除了引起身体损伤之外，还会再现这种现象。借鉴慢性应激和巴甫洛夫条件反射文献中的成熟工作，我们假设即使在爆炸暴露期间被麻醉，在爆炸环境中遇到的环境线索也可以被调节以引起厌恶/烦躁和创伤性应激的重新体验。我们使用气动冲击波管重现了与战场相关的开放式爆炸力，直接证明了重复爆炸暴露是固有压力源，导致对以前与爆炸相关的线索产生慢性厌恶/烦躁样反应。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也会导致同时出现厌恶/烦躁样应激反应。这些结果扩展了对重复爆炸暴露的高度复杂性质的认识；并进一步支持了目前多个实验室使用的动物模型方法的潜在转化相关性，这些方法旨在阐明重复爆炸暴露的机制（分子和行为）。
