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使用一种新的小鼠损伤实验模型鉴定爆炸伤和爆炸诱导性神经创伤的病理生物学。

The pathobiology of blast injuries and blast-induced neurotrauma as identified using a new experimental model of injury in mice.

机构信息

Biomedicine Business Area, National Security Technology Department, Johns Hopkins University Applied Physics Laboratory (JHU/APL), Laurel, MD 20723, USA.

出版信息

Neurobiol Dis. 2011 Feb;41(2):538-51. doi: 10.1016/j.nbd.2010.10.025. Epub 2010 Nov 11.

DOI:10.1016/j.nbd.2010.10.025
PMID:21074615
Abstract

Current experimental models of blast injuries used to study blast-induced neurotrauma (BINT) vary widely, which makes the comparison of the experimental results extremely challenging. Most of the blast injury models replicate the ideal Friedländer type of blast wave, without the capability to generate blast signatures with multiple shock fronts and refraction waves as seen in real-life conditions; this significantly reduces their clinical and military relevance. Here, we describe the pathophysiological consequences of graded blast injuries and BINT generated by a newly developed, highly controlled, and reproducible model using a modular, multi-chamber shock tube capable of tailoring pressure wave signatures and reproducing complex shock wave signatures seen in theater. While functional deficits due to blast exposure represent the principal health problem for today's warfighters, the majority of available blast models induces tissue destruction rather than mimic functional deficits. Thus, the main goal of our model is to reliably reproduce long-term neurological impairments caused by blast. Physiological parameters, functional (motor, cognitive, and behavioral) outcomes, and underlying molecular mechanisms involved in inflammation measured in the brain over the 30 day post-blast period showed this model is capable of reproducing major neurological changes of clinical BINT.

摘要

目前用于研究爆炸伤诱导的神经损伤(BINT)的实验模型差异很大,这使得实验结果的比较极具挑战性。大多数爆炸伤模型复制了理想的 Friedländer 型爆炸波,而没有产生现实条件下具有多个冲击波前沿和折射波的爆炸特征的能力;这大大降低了它们的临床和军事相关性。在这里,我们描述了使用模块化多腔室冲击波管开发的新型高度可控且可重复的模型产生的分级爆炸伤和 BINT 的病理生理后果,该冲击波管能够定制压力波特征并再现战场上看到的复杂冲击波特征。虽然爆炸暴露引起的功能障碍是当今作战人员的主要健康问题,但大多数可用的爆炸模型会导致组织破坏,而不是模拟功能障碍。因此,我们模型的主要目标是可靠地复制爆炸引起的长期神经损伤。在爆炸后 30 天的时间内,在大脑中测量的生理参数、功能(运动、认知和行为)结果以及炎症相关的潜在分子机制表明,该模型能够复制临床 BINT 的主要神经变化。

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