1 Faculty of Health Sciences, Ministry of Health, Anxiety and Stress Research Unit, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
2 Department of Mechanical Engineering, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
J Neurotrauma. 2019 Jan 15;36(2):380-394. doi: 10.1089/neu.2018.5672. Epub 2018 Sep 5.
The complex interactions and overlapping symptoms of comorbid post-traumatic stress disorder (PTSD) and mild traumatic brain injury (mTBI) induced by an explosive blast wave have become a focus of attention in recent years, making clinical distinction and effective intervention difficult. Because dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis is thought to underlie trauma-related (psycho)pathology, we evaluated both the endogenous corticosterone response and the efficacy of exogenous hydrocortisone treatment provided shortly after blast exposure. We employed a controlled experimental blast-wave paradigm in which unanesthetized animals were exposed to visual, auditory, olfactory, and tactile effects of an explosive blast wave produced by exploding a thin copper wire. Endogenous corticosterone concentrations were evaluated at different time points (before, and 3 h, 5 h and 17 days) after blast exposure. Subsequently, the efficacy of exogenous hydrocortisone (25 mg/kg or 125 mg/kg) injected intraperitoneally 1 h after exposure was compared with that of a similarly timed saline injection. Validated cognitive and behavioral tests were used to assess both PTSD and mTBI phenotypes on days 7-14 following the blast. Retrospective analysis revealed that animals demonstrating the PTSD phenotype exhibited a significantly blunted endogenous corticosterone response to the blast compared with all other groups. Moreover, a single 125 mg/kg dose of hydrocortisone administered 1 h after exposure significantly reduced the occurrence of the PTSD phenotype. Hydrocortisone treatment did not have a similar effect on the mTBI phenotype. Results of this study indicate that an inadequate corticosteroid response following blast exposure increases risk for PTSD phenotype, and corticosteroid treatment is a potential clinical intervention for attenuating PTSD. The differences in patterns of physiological and therapeutic response between PTSD and mTBI phenotypes lend credence to the retrospective behavioral and cognitive classification criteria we designed, and is in keeping with the assumption that mTBI and PTSD phenotypes may reflect distinct underlying biological and clinical profiles.
近年来，爆炸冲击波引起的创伤后应激障碍（PTSD）和轻度创伤性脑损伤（mTBI）的复杂相互作用和重叠症状已成为关注焦点，使得临床区分和有效干预变得困难。由于下丘脑-垂体-肾上腺（HPA）轴的失调被认为是与创伤相关的（精神）病理学的基础，我们评估了爆炸暴露后不久提供的内源性皮质酮反应和外源性氢化可的松治疗的疗效。我们采用了一种对照实验性爆炸波范式，在该范式中，未麻醉的动物暴露于爆炸产生的薄铜丝爆炸的视觉、听觉、嗅觉和触觉效应。在爆炸暴露后不同时间点（暴露前、暴露后 3h、5h 和 17d）评估内源性皮质酮浓度。随后，比较了腹腔内注射外源性氢化可的松（25mg/kg 或 125mg/kg）1h 后与同时注射生理盐水的疗效。在爆炸后第 7-14 天，使用经过验证的认知和行为测试来评估 PTSD 和 mTBI 表型。回顾性分析显示，表现出 PTSD 表型的动物对爆炸的内源性皮质酮反应明显减弱，与其他所有组相比。此外，在暴露后 1h 给予单次 125mg/kg 剂量的氢化可的松可显著减少 PTSD 表型的发生。氢化可的松治疗对 mTBI 表型没有类似的影响。这项研究的结果表明，爆炸暴露后皮质酮反应不足会增加 PTSD 表型的风险，皮质酮治疗可能是减轻 PTSD 的潜在临床干预措施。PTSD 和 mTBI 表型之间生理和治疗反应模式的差异为我们设计的回顾性行为和认知分类标准提供了依据，并且符合 mTBI 和 PTSD 表型可能反映不同的潜在生物学和临床特征的假设。
