Contribution of blast wave components to mild traumatic brain injury

描述(申请人提供)：爆炸导致的创伤性脑损伤(BTBI)已成为伊拉克/持久自由行动(OIF/OEF)的“标志性损伤”，由于工业和恐怖主义爆炸，平民也越来越频繁。爆炸冲击波对bTBI的作用机制正在使用大小动物模型进行研究。BTBI的小型动物模型主要使用压缩空气驱动的激波管造成伤害，而大型动物模型在露天和各种封闭空间使用化学炸药(即C-4塑料炸药的主要爆炸成分RDX)。模型设计和冲击波来源的不同使得比较每个模型的结果都很困难。以前的bTBI研究主要集中在峰值冲击波压力和脑损伤之间的关系。然而，我们假设冲击波的其他成分也可能对脑损伤起作用。为了确定爆炸的哪些成分会造成伤害，我们开发并表征了麦克米兰爆炸装置(MBD)，这是一种可以利用压缩气体(空气、氦)或化学炸药(RDX、氢氧)作为冲击波来源的激波管。压缩气体源产生的冲击波与MBD内化学炸药产生的冲击波有很大不同。这项提议试图确定冲击波的哪些成分对大鼠的大脑病理起作用。这一建议的总体假设是，除了峰值超压外，正相持续时间在爆炸造成的伤害中也起着作用。为了验证这一假设，目标1将比较氢气和压缩空气产生的类似峰值超压的爆炸。氢氧驱动的冲击波具有较短的正相持续时间，因此预计会产生较少的脑损伤。这将使用一系列峰值超压进行评估。脑损伤将使用弥漫性轴索损伤(DAI)、血脑屏障(BBB)损害、氧化应激和神经元死亡等指标进行评估。目标2将在目标1的基础上扩展，将压缩空气驱动的冲击波的正相持续时间缩短到与氢氧驱动的爆炸相当的长度，并比较由此产生的脑损伤。目标3将检验这样一种假设，即冲击波的反射延长了超压阶段的持续时间，将加剧爆炸造成的脑损伤程度。

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.