Neurobiological Consequences of Blast Injury in a Rat Model of mTBI

项目摘要/摘要 轻度创伤性脑损伤(MTBI)被称为伊拉克战争中的标志性损伤 (伊拉克自由行动；OIF)和阿富汗(持久自由行动；OEF)。在这两个地方 在手术室中，颅脑损伤一直是BLAST死亡率和发病率的重要原因 相关伤害是最常见的原因。动物研究清楚地表明，爆炸超压 (国际收支)波被传输到大脑。MTBI病例的一个显著特征是#年 伊拉克和阿富汗战争的退伍军人是MTBI与创伤后的高度关联 应激障碍(PTSD)。事实上，回国后创伤后应激障碍和抑郁症的高患病率 患有MTBI的OIF/OEF退伍军人现在有很好的记录，以及两者之间的区别 事实证明，精神障碍是一种具有临床挑战性的练习。OIF/OEF创伤后应激障碍的高患病率 患有MTBI的退伍军人可以通过同时接触TBI事件和 创伤后应激障碍应激源。然而，另一种假说是冲击波相关的MTBI损害大脑。 在调节对心理压力源的反应方面非常重要的结构，因此 当暴露于随后的应激源时，会增加患上创伤后应激障碍的可能性。这里 利用我们这一项目的合作者开发的冲击波诱导的MTBI大鼠模型，Dr。 史蒂芬·阿莱斯船长(R)，国防部资助的海军医疗中心研究员 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。 我们将对单独或重复暴露的大鼠进行详细的行为特征描述 BOP损伤，强调与认知和认知相关的行为和认知特征 与人类创伤后应激障碍和创伤相关的行为变化(目标1)，并确定 暴露于BOP易使人在暴露于一种 创伤后应激障碍应激源(一种捕食者气味)使用已建立的大鼠模型(目标2)。此外，我们还将 确定急性或反复暴露防喷剂对前额叶皮质的结构影响， 杏仁核和海马体，被认为是 创伤后应激障碍的神经生物学基础(目标3)，并检查海马神经发生是否可能 防喷器暴露后发生改变(目标4)。总的来说，这些研究将有助于更好地 BLAST相关MTBI的神经生物学效应及其是否与BLAST相关 脑损伤本身可能是这种患者群体中创伤后应激障碍高患病率的原因之一。

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.