Expansion of a fly TBI model to four levels of injury severity reveals synergistic effects of repetitive injury for moderate injury conditions
Expansion of a fly TBI model to four levels of injury severity reveals synergistic effects of repetitive injury for moderate injury conditions
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DOI：
10.1080/19336934.2019.1664363
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发表时间：
2019-04
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通讯作者：
Lauren J Putnam;Ashley M Willes;Brooke E. Kalata;Nathaniel D. Disher;Douglas J. Brusich
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作者：
Lauren J Putnam;Ashley M Willes;Brooke E. Kalata;Nathaniel D. Disher;Douglas J. Brusich
据报道，美国每年有数百万起创伤性脑损伤(TBI)事件。然而，轻微的脑外伤事件通常不被报道，而轻微和重复的轻微脑损伤情况很难建立模型。果蝇为脑外伤的研究提供了新的动力。最具特点的飞行创伤模型是高冲击创伤(HIT)方法。我们复制了HIT方法，并在损伤严重程度的标准水平上证实了之前的几个发现。然后，我们扩展了HIT模型，通过表征三个降低的伤害严重程度的死亡率。重要的是，我们发现，在中度损伤条件下，重复的脑外伤降低了死亡率，降低了损伤严重性，并对死亡率产生了协同作用。最后，我们通过评估重型颅脑损伤后24小时内的死亡率和趋地性表现，比较了中度、重复性和单一重型颅脑损伤。我们发现，创伤的数量和严重程度可能会导致不同的死亡模式，而所有的创伤条件都会导致与伤后0.5小时和6小时未受伤的果蝇相比，其趋地性受损。因此，我们在果蝇中推广了一个具有良好特征的创伤性脑损伤模型，并展示了该模型在不同伤情、受伤人数和损伤后时间点对创伤性脑损伤进行独特洞察的实用性。
Several million traumatic brain injury (TBI) events are reported in the United States annually. However, mild TBI events often go unreported, and mild and repetitive mild TBI conditions are challenging to model. Fruit flies (Drosophila melanogaster) have gained traction for the study of TBI. The best-characterized fly TBI model is the high-impact trauma (HIT) method. We replicated the HIT method and confirmed several previous findings at the standard level of injury severity. We then expanded upon the HIT model by characterizing mortality across three reduced levels of injury severity. Importantly, we found reduced mortality with reduced injury severity and synergistic effects on mortality in response to repetitive TBI by our moderate injury conditions. Last, we compared moderate, repetitive TBI to a single severe TBI via assessment of the pattern of mortality and geotaxis performance in the 24 h following TBI. We found the number and severity of injuries could result in different patterns of death, while all TBI conditions led to impaired geotaxis compared to uninjured flies at 0.5 h and 6 h post-TBI. Thus, we have extended a well-characterized model of TBI in flies, and shown the utility of this model for making unique insights into TBI across various severities, injury numbers, and time-points post-injury.