Hockey K S, Hubbard W B, Sajja V S, Sholar C A, Thorpe C, Vandevord P J, Rzigalinski B A
NanoNeuroLab.
Biomed Sci Instrum. 2013;49:134-40.
Current models for blast injury involve the use of mammalian species, which are costly and require extensive monitoring and housing, making it difficult to generate large numbers of injuries. The fruit fly, Drosophila melanogaster, has been utilized for many models of human disease including neurodegenerative disorders such as Parkinsons and Alzheimers diseases. In this study, a model of blast injury was designed based on Drosophila, to provide a mechanism to investigate blast injury in large numbers and assess biochemical mechanisms of brain injury. Such studies may be used to identify specific pathways involved in blast-associated neurodegeneration, allowing more effective use of mammalian models. A custom-built blast wave simulator (ORA Inc.), comprised of a driver, test section, and wave eliminator, was used to create a blast wave. An acetate membrane was placed between the driver and the rectangular test section before compressed helium caused the membrane to rupture creating the blast wave. Membrane thickness correlates with the blast wave magnitude, which averaged 120 kPa for this experiment. Pressure sensors were inserted into the side of the tube in order to quantify the level of overpressure that the flies were exposed to. Five day old flies were held in a rectangular enclosed mesh fixture (10 flies per enclosure) which was placed in the center of the test section for blast delivery. Sham controls were exposed to same conditions with exception of blast. Lifespan and negative geotaxis, a measurement of motor function, was measured in flies after blast injury. Mild blast resulted in death of 28% of the flies. In surviving flies, motor function was initially reduced, but flies regained normal function by 8 days after injury. Although surviving flies regained normal motor function, flies subjected to mild blast died earlier than uninjured controls, with a 15.4% reduction in maximum lifespan and a 17% reduction in average lifespan, mimicking the scenario observed in humans exposed to mild blast. Although further work is needed, results suggest that utilizing Drosophila as a blast model may provide a rapid, effective means of assessing physiological and biochemical changes induced by mild blast.
当前的爆炸伤模型使用哺乳动物,成本高昂且需要大量监测和饲养,难以造成大量损伤。果蝇,即黑腹果蝇,已被用于许多人类疾病模型,包括帕金森病和阿尔茨海默病等神经退行性疾病。在本研究中,基于果蝇设计了一种爆炸伤模型,以提供一种机制来大量研究爆炸伤并评估脑损伤的生化机制。此类研究可用于识别与爆炸相关的神经退行性变所涉及的特定途径,从而更有效地利用哺乳动物模型。使用一个定制的爆炸波模拟器(ORA公司),它由一个驱动器、测试区和消波器组成,来产生爆炸波。在压缩氦气使膜破裂产生爆炸波之前,在驱动器和矩形测试区之间放置了一个醋酸盐膜。膜的厚度与爆炸波强度相关,本实验中平均强度为120千帕。压力传感器插入管的侧面,以量化果蝇所暴露的超压水平。五天大的果蝇被放置在一个矩形封闭的网状固定装置中(每个装置放10只果蝇),该装置置于测试区中心用于爆炸传递。假对照组除不进行爆炸外,暴露于相同条件。在果蝇遭受爆炸伤后,测量其寿命和负趋地性(一种运动功能测量指标)。轻度爆炸导致28%的果蝇死亡。在存活的果蝇中,运动功能最初下降,但在受伤后8天果蝇恢复了正常功能。尽管存活的果蝇恢复了正常运动功能,但遭受轻度爆炸的果蝇比未受伤的对照组死亡更早,最大寿命降低了15.4%,平均寿命降低了17%,这与轻度爆炸的人类情况相似。尽管还需要进一步研究,但结果表明利用果蝇作为爆炸模型可能提供一种快速、有效的方法来评估轻度爆炸引起的生理和生化变化。