Song Hailong, Konan Landry M, Cui Jiankun, Johnson Catherine E, Langenderfer Martin, Grant DeAna, Ndam Tina, Simonyi Agnes, White Tommi, Demirci Utkan, Mott David R, Schwer Doug, Hubler Graham K, Cernak Ibolja, DePalma Ralph G, Gu Zezong
Department of Pathology & Anatomical Sciences, University of Missouri School of Medicine, Columbia, MO 65212, USA.
Department of Pathology & Anatomical Sciences, University of Missouri School of Medicine, Columbia, MO 65212, USA; Truman VA Hospital Research Service, Columbia, MO 65201, USA.
Behav Brain Res. 2018 Jul 16;347:148-157. doi: 10.1016/j.bbr.2018.03.007. Epub 2018 Mar 8.
Explosive blast-induced mild traumatic brain injury (mTBI), a "signature wound" of recent military conflicts, commonly affects service members. While past blast injury studies have provided insights into TBI with moderate- to high-intensity explosions, the impact of primary low-intensity blast (LIB)-mediated pathobiology on neurological deficits requires further investigation. Our prior considerations of blast physics predicted ultrastructural injuries at nanoscale levels. Here, we provide quantitative data using a primary LIB injury murine model exposed to open field detonation of 350 g of high-energy explosive C4. We quantified ultrastructural and behavioral changes up to 30 days post blast injury (DPI). The use of an open-field experimental blast generated a primary blast wave with a peak overpressure of 6.76 PSI (46.6 kPa) at a 3-m distance from the center of the explosion, a positive phase duration of approximate 3.0 milliseconds (ms), a maximal impulse of 8.7 PSI × ms and a sharp rising time of 9 × 10 ms, with no apparent impact/acceleration in exposed animals. Neuropathologically, myelinated axonal damage was observed in blast-exposed groups at 7 DPI. Using transmission electron microscopy, we observed and quantified myelin sheath defects and mitochondrial abnormalities at 7 and 30 DPI. Inverse correlations between blast intensities and neurobehavioral outcomes including motor activities, anxiety levels, nesting behavior, spatial learning and memory occurred. These observations uncover unique ultrastructural brain abnormalities and associated behavioral changes due to primary blast injury and provide key insights into its pathogenesis and potential treatment.
爆炸所致轻度创伤性脑损伤（mTBI）是近期军事冲突中的一种“典型创伤”，常影响现役军人。虽然过去关于爆炸伤的研究为中高强度爆炸导致的创伤性脑损伤提供了见解，但原发性低强度爆炸（LIB）介导的病理生物学对神经功能缺损的影响仍需进一步研究。我们之前对爆炸物理学的思考预测了纳米级别的超微结构损伤。在此，我们使用暴露于350克高能炸药C4露天爆炸的原发性LIB损伤小鼠模型提供定量数据。我们对爆炸伤后30天内的超微结构和行为变化进行了量化。使用露天实验爆炸在距爆炸中心3米处产生了峰值超压为6.76磅力/平方英寸（46.6千帕）的原发性冲击波，正相持续时间约为3.0毫秒（ms），最大冲量为8.7磅力/平方英寸×毫秒，上升时间为9×10毫秒，暴露动物未出现明显撞击/加速。神经病理学上，在爆炸暴露组伤后7天观察到有髓轴突损伤。使用透射电子显微镜，我们在伤后7天和30天观察并量化了髓鞘缺陷和线粒体异常。爆炸强度与包括运动活动、焦虑水平、筑巢行为、空间学习和记忆在内的神经行为结果之间存在负相关。这些观察结果揭示了原发性爆炸伤导致的独特超微结构脑异常和相关行为变化，并为其发病机制和潜在治疗提供了关键见解。
