Siedhoff Heather R, Chen Shanyan, Balderrama Ashley, Jackson Dejun, Li Runting, Sun Grace Y, DePalma Ralph G, Cui Jiankun, Gu Zezong
Truman VA Hospital Research Service, Columbia, Missouri, USA.
Department of Pathology & Anatomical Sciences, University of Missouri School of Medicine, Columbia, Missouri, USA.
Neurotrauma Rep. 2024 Dec 12;5(1):1195-1204. doi: 10.1089/neur.2024.0134. eCollection 2024.
Primary blast exposure is a predominant cause of mild traumatic brain injury (mTBI) among veterans and active-duty military personnel, and affected individuals may develop long-lasting behavioral disturbances that interfere with quality of life. Our prior research with the "Missouri Blast" model demonstrated behavioral changes relevant to deficits in cognitive and affective domains after exposure to low-intensity blast (LIB). In this study, behavioral evaluations were extended to 3 months post-LIB injury using multifaceted conventional and advanced behavioral paradigms. C57BL/6J male mice, aged 2 months old, were subjected to a non-inertial primary LIB-induced mTBI by detonating 350 g of C-4 at a 3-m distance on 1-m-tall platforms. Three months after injury, mice were evaluated using the open-field test (OFT), social interaction test, and advanced Erasmus Ladder paradigm. With OFT, no apparent anxiety-like changes were detected with the LIB-exposed mice and sham controls, and both groups displayed similar center-zone activities. Although no social interaction parameters reached significance, a majority of LIB-exposed mice less than 50% of interactions compared with their interaction partners, suggesting decreased sociability. With the Erasmus Ladder test to assess motor functions, associative learning, and stimulus response, LIB-exposed mice appeared to display increased instances of leaving before the cue, reminiscent of "escape behavior," indicative of anxiety-related activity different from that OFT detected. Overall, these results revealed subtle multifaceted long-lasting anxiety-relevant effects following LIB exposure. The "Missouri Blast" platform offers a basis for future research to investigate the underlying biological mechanism(s) leading to domain-specific behavioral changes.
原发性爆炸暴露是退伍军人和现役军事人员轻度创伤性脑损伤（mTBI）的主要原因，受影响的个体可能会出现长期的行为障碍，从而影响生活质量。我们之前对“密苏里爆炸”模型的研究表明，在暴露于低强度爆炸（LIB）后，会出现与认知和情感领域缺陷相关的行为变化。在本研究中，使用多方面的传统和先进行为范式，将行为评估延长至LIB损伤后3个月。2月龄的C57BL/6J雄性小鼠在1米高的平台上3米远处引爆350克C-4，以诱导非惯性原发性LIB导致的mTBI。损伤后3个月，使用旷场试验（OFT）、社会互动试验和先进的伊拉斯谟阶梯范式对小鼠进行评估。在OFT中，暴露于LIB的小鼠和假手术对照组均未检测到明显的焦虑样变化，两组的中央区域活动相似。虽然没有社会互动参数达到显著水平，但与互动伙伴相比，大多数暴露于LIB的小鼠的互动次数减少了不到50%，这表明社交能力下降。通过伊拉斯谟阶梯试验评估运动功能、联想学习和刺激反应，暴露于LIB的小鼠似乎在提示前出现离开的次数增加，类似于“逃避行为”，这表明与OFT检测到的不同的焦虑相关活动。总体而言，这些结果揭示了LIB暴露后细微的多方面长期焦虑相关效应。“密苏里爆炸”平台为未来研究导致特定领域行为变化的潜在生物学机制提供了基础。
