Neurobiological Consequences of Blast Injury in a Rat Model of mTBI

项目概要/摘要 轻度创伤性脑损伤（MTBI）被称为伊拉克战争的标志性损伤 （伊拉克自由行动；OIF）和阿富汗（持久自由行动；OEF）。在两者中 在手术室中，TBI 是导致爆炸死亡和发病的一个重要原因 相关伤害是最常见的原因。动物研究清楚地表明爆炸超压 (BOP) 波传输到大脑。 MTBI 案件的一个显着特征是 伊拉克和阿富汗战争的退伍军人认为 MTBI 与创伤后的高度相关 应激障碍（PTSD）。事实上，创伤后应激障碍（PTSD）和抑郁症在回国者中的患病率很高。 OIF/OEF 退伍军人与 MTBI 现已有详细记录，两者之间的区别 疾病已被证明是一项具有临床挑战性的练习。 OIF/OEF 中 PTSD 患病率较高 患有 MTBI 的退伍军人可能是由于同时暴露于 TBI 事件以及 创伤后应激障碍压力源。然而，另一种假设是爆炸相关的 MTBI 会损害大脑 在调节对心理压力源的反应中发挥重要作用的结构，因此 当暴露于随后的压力源时，会增加患创伤后应激障碍（PTSD）的可能性。这里 使用由我们在该项目中的合作者开发的爆炸诱导 MTBI 大鼠模型，Dr. 斯蒂芬·阿勒斯 CAPT(r) 是国防部资助的海军医疗调查员 在马里兰州银泉研究中心，我们将通过四个具体目标来探索这一假设。 我们将对暴露于单次或重复的大鼠进行详细的行为表征 BOP 损伤，重点是与认知和认知相关的行为和认知特征 与人类 PTSD 和 TBI 相关的行为变化（目标#1）并确定是否 BOP 暴露容易导致 PTSD 样特征的发展 使用完善的大鼠模型（目标#2）来模拟 PTSD 压力源（捕食者的气味）。我们还将另外 确定急性或反复接触 BOP 对前额皮质的结构影响， 杏仁核和海马体，被认为是构成大脑的主要解剖基质 PTSD 的神经生物学基础（目标#3）并检查海马神经发生是否可能 在国际收支平衡暴露后进行改变（目标#4）。总的来说，这些研究将有助于更好地 了解急变相关 MTBI 的神经生物学效应以及急变是否相关 脑损伤本身可能导致该患者群体中 PTSD 的高患病率。

PROJECT SUMMARY/ABSTRACT Mild traumatic brain injury (MTBI) has been called the signature injury of the wars in Iraq (operation Iraqi freedom; OIF) and Afghanistan (operation enduring freedom; OEF). In both theatres of operation, TBI has been a significant cause of mortality and morbidity with blast related injury the most common cause. Animal studies clearly show that blast overpressure (BOP) waves are transmitted to brain. One striking feature of the MTBI cases being seen in veterans of the wars in Iraq and Afghanistan is the high association of MTBI with post-traumatic stress disorder (PTSD). Indeed the high prevalence of PTSD and depression in returning OIF/OEF veterans with MTBI is now well documented and the distinction between the two disorders has proven a clinically challenging exercise. The high prevalence of PTSD in OIF/OEF veterans with MTBI might be explained by co-incident exposures to both TBI events as well as PTSD stressors. However, an alternative hypothesis is that blast related MTBI damages brain structures that are important in mediating responses to psychological stressors and thus enhances the likelihood of developing PTSD when exposed to subsequent stressors. Here using a rat model of blast induced MTBI developed by our collaborator on this project, Dr. Stephen Ahlers CAPT(r) a Department of Defense funded investigator at the Naval Medical Research Center in Silver Spring MD, we will explore this hypothesis through four specific aims. We will perform a detailed behavioral characterization of rats exposed to single or repeated BOP injury with an emphasis on behavioral and cognitive traits related to the cognitive and behavioral changes associated with human PTSD and TBI (aim #1) and determine whether BOP exposure predisposes to the development of PTSD like traits following exposure to a PTSD stressor (a predator scent) using a well-established rat model (aim #2). We will in addition determine the structural effects of acute or repeated BOP exposure on the prefrontal cortex, amygdala and hippocampus, the principal anatomic substrates that are thought to underlie the neurobiological basis of PTSD (aim #3) and examine whether hippocampal neurogenesis may be altered following BOP exposure (aim #4). Collectively these studies will contribute to a better understanding of the neurobiological effects of blast related MTBI and whether blast related brain injury itself may contribute to the high prevalence of PTSD seen in this patient population.