Neurobiological Consequences of Blast Injury in a Rat Model of mTBI

mTBI 大鼠模型中爆炸损伤的神经生物学后果

• 批准号: 7888213
• 负责人: Gregory A. Elder
• 金额: --
• 依托单位: JAMES J PETERS VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-01 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7888213
• 关键词: Absence of pain sensation; Acoustics; Acute; Adult; Affect; Afghanistan; Amygdaloid structure; Anatomy; Animal Model; Animals; Anxiety; Area; Auditory; Behavior; Behavioral; Biological Assay; Blast Cell; Blast Injuries; Brain; Brain Injuries; Cells; Chronic; Cognitive; Complex; Cues; Dendrites; Dendritic Spines; Department of Defense; Depressed mood; Development; Disease; Distress; Employee Strikes; Event; Exercise; Exposure to; Felis catus; Freedom; Functional disorder; Funding; Health; High Prevalence; Hippocampus (Brain); Human; Injury; Iraq; Learning; Light; Link; Measures; Medial; Mediating; Medical Research; Medical center; Memory; Mental Depression; Modeling; Morbidity - disease rate; Motor; Motor Activity; Neurobiology; Phenotype; Physiological; Post-Traumatic Stress Disorders; Prefrontal Cortex; Production; Rattus; Reflex action; Regulation; Research Personnel; Rodent; Rodent Model; Role; Sensory; Short-Term Memory; Silver; Stress; Structure; Symptoms; Tail; Testing; Therapeutic Intervention; Traumatic Brain Injury; Urine; Veterans; War; Work; base; cognitive change; conditioned fear; design; evidence base; grasp; improved; injured; interest; male; morris water maze; mortality; neurogenesis; operation; patient population; programs; psychological stressor; response; sensory gating; stressor; therapeutic target; trait; way finding; young adult

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.

项目摘要/摘要 轻度创伤性脑损伤（MTBI）被称为伊拉克战争的签名伤害 （伊拉克自由行动； OIF行动）和阿富汗（持久的自由行动； OEF）。在这两个中 运营剧院，TBI一直是死亡率和发病率的重要原因 相关伤害最常见的原因。动物研究清楚地表明，爆炸过压 （BOP）波传播到大脑。 MTBI案件的一个引人注目的特征 伊拉克和阿富汗战争的退伍军人是MTBI与创伤后的高级协会 应激障碍（PTSD）。实际上，PTSD和抑郁症的高流行率 现在已经有充分的文献记录了MTBI的OIF/OEF退伍军人，并且两者之间的区别 疾病已证明是临床上具有挑战性的运动。 OIF/OEF中PTSD的高患病率 与MTBI的退伍军人可以通过对TBI事件的同时暴露以及 PTSD应激源。但是，另一种假设是爆炸相关的MTBI损害大脑 在介导对心理压力源的反应中很重要的结构，从而 在暴露于随后的压力源时发展PTSD的可能性。这里 使用我们的合作者在该项目上开发的BLAST诱导MTBI的大鼠模型，博士 斯蒂芬·艾尔斯（Stephen Ahlers）上尉（R）国防部资助的海军医疗调查员 Silver Spring MD的研究中心，我们将通过四个特定目标探讨这一假设。 我们将对暴露于单个或重复的大鼠进行详细的行为表征 BOP伤害，重点是与认知和认知和认知性状 与人PTSD和TBI相关的行为变化（AIM＃1），并确定是否是否 暴露于PTSD之类的特征之类的PTSD的发展，暴露于A PTSD应激源（一种捕食者气味）使用良好的大鼠模型（AIM＃2）。我们还将 确定急性或重复BOP暴露对前额叶皮层的结构效应， 杏仁核和海马，这是主要的解剖基质，被认为是 PTSD的神经生物学基础（AIM＃3），检查海马神经发生是否可以 BOP暴露后会更改（AIM＃4）。这些研究集体将有助于更好 了解相关MTBI的神经生物学效应以及BLAST是否相关 脑损伤本身可能导致该患者人群中PTSD的高流行。