Shultz Sandy R, Sun Mujun, Wright David K, Brady Rhys D, Liu Shijie, Beynon Sinead, Schmidt Shannon F, Kaye Andrew H, Hamilton John A, O'Brien Terence J, Grills Brian L, McDonald Stuart J
Department of Medicine, The Royal Melbourne Hospital, The University of Melbourne, Parkville, VIC, Australia.
1] Anatomy and Neuroscience, The University of Melbourne, Parkville, VIC, Australia [2] The Florey Institute of Neuroscience and Mental Health, Parkville, VIC, Australia.
J Cereb Blood Flow Metab. 2015 Aug;35(8):1339-47. doi: 10.1038/jcbfm.2015.56. Epub 2015 Apr 8.
Multitrauma is a common medical problem worldwide, and often involves concurrent traumatic brain injury (TBI) and bone fracture. Despite the high incidence of combined TBI and fracture, preclinical TBI research commonly employs independent injury models that fail to incorporate the pathophysiologic interactions occurring in multitrauma. Here, we developed a novel mouse model of multitrauma, and investigated whether bone fracture worsened TBI outcomes. Male mice were assigned into four groups: sham-TBI+sham-fracture (SHAM); sham-TBI+fracture (FX); TBI+sham-fracture (TBI); and TBI+fracture (MULTI). The injury methods included a closed-skull weight-drop TBI model and a closed tibial fracture. After a 35-day recovery, mice underwent behavioral testing and magnetic resonance imaging (MRI). MULTI mice displayed abnormal behaviors in the open-field compared with all other groups. On MRI, MULTI mice had enlarged ventricles and diffusion abnormalities compared with all other groups. These changes occurred in the presence of heightened neuroinflammation in MULTI mice at 24 hours and 35 days after injury, and elevated edema and blood-brain barrier disruption at 24 hours after injury. Together, these findings indicate that tibial fracture worsens TBI outcomes, and that exacerbated neuroinflammation may be an important factor that contributes to these effects, which warrants further investigation.
多发伤是全球常见的医学问题，常伴有创伤性脑损伤（TBI）和骨折。尽管TBI合并骨折的发生率很高，但临床前TBI研究通常采用独立的损伤模型，未能纳入多发伤中发生的病理生理相互作用。在此，我们开发了一种新型的多发伤小鼠模型，并研究骨折是否会恶化TBI的预后。将雄性小鼠分为四组：假TBI+假骨折（SHAM）；假TBI+骨折（FX）；TBI+假骨折（TBI）；以及TBI+骨折（MULTI）。损伤方法包括闭合性颅骨重物打击TBI模型和闭合性胫骨骨折。经过35天的恢复后，对小鼠进行行为测试和磁共振成像（MRI）。与所有其他组相比，MULTI组小鼠在旷场试验中表现出异常行为。在MRI上，与所有其他组相比，MULTI组小鼠脑室扩大且有弥散异常。这些变化发生在损伤后24小时和35天时MULTI组小鼠神经炎症加剧，以及损伤后24小时水肿加重和血脑屏障破坏的情况下。总之，这些发现表明胫骨骨折会恶化TBI的预后，且神经炎症加剧可能是导致这些影响的重要因素，这值得进一步研究。
