Contribution of blast wave components to mild traumatic brain injury

爆炸引起的创伤性脑损伤（bTBI）已成为伊拉克/持久自由行动（OIF/OEF）的“标志性损伤”，并且由于工业和恐怖爆炸，在平民中也越来越常见。爆炸冲击波导致bTBI的机制正在使用大型和小型动物模型进行研究。bTBI的小动物模型主要利用压缩空气驱动的冲击管来产生损伤，而大动物模型使用化学爆炸物（即，黑索今-C-4可塑炸药的主要爆炸成分）在露天和各种封闭空间爆炸。由于模型设计和冲击波源的不同，很难对每个模型的结果进行比较。以前的bTBI研究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，我们开发并表征了McMillan爆炸装置（MBD），这是一种可以利用压缩气体（空气，氦气）或化学爆炸物（RDX，氢氧）作为冲击波源的激波管。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。该提案旨在确定冲击波的哪些成分有助于大鼠的脑病理学。该建议的总体假设是，除了峰值超压之外，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，目标1将比较由氢氧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，因此预计产生较少的脑损伤。这将使用一系列峰值超压进行评估。将使用标记物弥漫性轴索损伤（DAI）、血脑屏障（BBB）受损、氧化应激和神经元死亡来评估脑损伤。目标2将通过将压缩空气驱动冲击波的正相持续时间缩短到与氢氧驱动冲击波相当的长度并比较由此产生的脑损伤来扩展目标1。目标3将检验这样一种假设，即爆炸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的程度。 公共卫生相关性：爆炸引起的创伤性脑损伤（bTBI）在军事和平民人群中变得越来越普遍，而与bTBI相关的病理机制的潜在机制在很大程度上仍然未知。该提案将通过使用压缩气体和化学爆炸源的冲击波来评估冲击波中导致脑损伤的成分。这些结果将有助于防护结构和个人防护装备的设计，以减轻爆炸波成分的影响，有助于bTBI。

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. PUBLIC HEALTH RELEVANCE: Blast-induced traumatic brain injury (bTBI) is becoming more prevalent among military and civilian populations, while the mechanisms underlying the pathologic mechanisms associated with bTBI remain largely unknown. This proposal will evaluate components of the blast wave that contribute to brain injury by using both compressed gas and chemical explosive sources for the blast wave. These results will aid in the design of protective structures and personal protective gear to mitigate the effects of blast wave components which contribute to bTBI.