Desmoulin Geoffrey T, Dionne Jean-Philippe
Department of Biomedical Engineering, Wayne State University, Detroit, Michigan, USA.
J Trauma. 2009 Nov;67(5):1113-22. doi: 10.1097/TA.0b013e3181bb8e84.
With the onset of improved protective equipment against fragmentation, blast-induced neurotrauma has emerged as the "signature wound" of the current conflicts in the Middle East. Current research has focused on this phenomenon; however, the exact mechanism of injury and ways to mitigate the ensuing pathophysiology remain largely unknown. The data presented and literature reviewed formed the fundamentals of a successful grant from the U.S. Office of Naval Research to Wayne State University.
This work is a culmination of specialized blast physics and energy-tissue coupling knowledge, recent pilot data using a 12-m shock tube and an instrumented Hybrid III crash test dummy, modeling results from Conventional Weapons effects software, and an exhaustive Medline and government database literature review.
The work supports our hypothesis of the mechanism of injury (described in detail) but sheds light on current hypotheses and how we investigate them. We expose two areas of novel mitigation development. First, there is a need to determine a physiologic and mechanism-based injury tolerance level through a combination of animal testing and biofidelic surrogate development. Once the injury mechanism is defined experimentally and an accurate physiologic threshold for brain injury is established, innovative technologies to protect personnel at risk can be appropriately assessed. Second, activated pathophysiological pathways are thought to be responsible for secondary neurodegeneration. Advanced pharmacological designs will inhibit the key cell signaling pathways. Simultaneously, evaluation of pharmacological candidates will confirm or deny current hypotheses of primary mechanisms of secondary neurodegeneration.
A physiologic- or biofidelic-based blast-induced tolerance curve may redefine current acceleration-based curves that are only valid to assess tertiary blast injury. Identification of additional pharmaceutical candidates will both confirm or deny current hypotheses on neural pathways of continued injury and help to develop novel prophylactic treatments.
随着针对破片的防护装备得到改进，爆炸所致神经创伤已成为中东当前冲突中的“典型创伤”。目前的研究聚焦于这一现象；然而，损伤的确切机制以及减轻随之而来的病理生理学变化的方法在很大程度上仍不为人知。所呈现的数据和所回顾的文献构成了美国海军研究办公室向韦恩州立大学成功授予资助的基础。
这项工作是专门的爆炸物理学和能量 - 组织耦合知识、使用12米激波管和仪器化的Hybrid III碰撞试验假人的近期初步数据、常规武器效应软件的建模结果以及对医学文献数据库和政府数据库进行详尽文献回顾的成果。
这项工作支持了我们关于损伤机制的假设（详细描述），但也揭示了当前的假设以及我们对其的研究方式。我们揭示了两个新的减轻损伤的发展领域。首先，需要通过动物试验和生物逼真替代品的开发相结合来确定基于生理和机制的损伤耐受水平。一旦通过实验确定了损伤机制并建立了脑损伤的准确生理阈值，就可以适当地评估保护高危人员的创新技术。其次，激活的病理生理途径被认为是继发性神经退行性变的原因。先进的药物设计将抑制关键的细胞信号通路。同时，对药物候选物的评估将证实或否定当前关于继发性神经退行性变主要机制的假设。
基于生理或生物逼真度的爆炸所致耐受曲线可能会重新定义当前仅用于评估三级爆炸伤的基于加速度的曲线。确定更多的药物候选物将既证实或否定当前关于持续损伤神经通路的假设，又有助于开发新的预防性治疗方法。
