Contribution of blast wave components to mild traumatic brain injury

描述（由申请人提供）：爆炸引起的创伤性脑损伤（bTBI）已经成为伊拉克/持久自由行动（OIF/OEF）的“标志性伤害”，并且由于工业和恐怖主义爆炸在平民中也越来越频繁。爆炸冲击波导致脑外伤的机制正在使用大型和小型动物模型进行研究。bTBI的小动物模型主要使用压缩空气驱动激波管来产生伤害，而大型动物模型在露天和各种封闭空间中使用化学炸药（即RDX - C-4塑料炸药的主要爆炸成分）。由于模型设计和激波源的不同，使得各模型的结果难以比较。以往的脑外伤研究主要集中在峰值爆炸压力与脑损伤之间的关系。然而，我们假设冲击波的其他成分也可能导致脑损伤。为了确定爆炸的哪些成分会造成伤害，我们开发了麦克米伦爆炸装置（MBD），并对其进行了表征，这是一种冲击波管，可以利用压缩气体（空气、氦气）或化学炸药（RDX、氢氧）作为冲击波源。压缩气源产生的冲击波与MBD内化学炸药产生的冲击波有很大不同。这项提议旨在确定冲击波的哪些成分导致了大鼠的脑部病理。该建议的总体假设是，除了峰值超压外，正相持续时间在爆炸产生的损伤中起作用。为了检验这一假设，Aim 1将比较氢氧和压缩空气产生的类似峰值超压爆炸。氧驱动的爆炸具有较短的正相持续时间，因此预计产生较少的脑损伤。这将使用一系列峰值超压来评估。脑损伤将通过弥漫性轴索损伤（DAI）、血脑屏障（BBB）损伤、氧化应激和神经元死亡等标志物进行评估。Aim 2将在Aim 1的基础上进行扩展，将压缩空气驱动冲击波的正相持续时间缩短至与氧气驱动爆炸相当的长度，并比较由此产生的脑损伤。目标3将检验爆炸波的反射，这延长了超压阶段的持续时间，将加剧爆炸产生的脑损伤程度的假设。

DESCRIPTION (provided by applicant): Blast-induced Traumatic brain injury (bTBI) has become the "signature injury" of Operations Iraqi/Enduring Freedom (OIF/OEF) and is also increasingly frequent in civilians as a result of industrial and terrorist explosions. The mechanisms by which blast shockwaves contribute to bTBI is being investigated using both large and small animal models. Small animal models of bTBI predominantly utilize compressed air-driven shock tubes to generate an injury, while large animal models employ chemical explosives (i.e., RDX - the main explosive component of C-4 plastic explosives) in both open-air and a variety of enclosed spaces. The differences in model design and shockwave source make comparison of results from each model difficult. Previous bTBI studies have focused on the relationship between peak blast pressure and brain injury. However, we hypothesize that other components of the shock wave may also contribute to the brain injury. In an effort to determine which components of the blast contribute to the injury, we developed and characterized the McMillan Blast Device (MBD), a shock tube that can utilize compressed gas (air, helium) or chemical explosives (RDX, oxyhydrogen) as the shockwave source. Shockwaves produced from compressed gas sources differ substantially from those produced by chemical explosives within the MBD. This proposal seeks to determine which components of the shock wave contribute to brain pathology in rats. The overall hypothesis of this proposal is that positive phase duration, in addition to peak overpressure, plays a role in the injury produced by blasts. To examine this hypothesis, Aim 1 will compare blasts of similar peak overpressures produced by oxhydrogen and compressed air. The oxyhydrogen-driven blasts have a shorter positive phase duration and are therefore anticipated to produce less brain injury. This will be evaluated using a range of peak overpressures. Brain injury will be assessed using markers diffuse axonal injury (DAI), blood-brain barrier (BBB) compromise, oxidative stress and neuron death. Aim 2 will expand upon Aim 1 by shortening the positive phase duration of a compressed air-driven shockwave to a length comparable to oxyhydrogen-driven blasts and comparing resultant brain injury. Aim 3 will examine the hypothesis that reflection of the blast waves, which extends the duration of the overpressure phase, will exacerbate the extent of brain injury produced by a blast.