title: Tibial fracture exacerbates traumatic brain injury outcomes and neuroinflammation in a novel mouse model of multitrauma.
abstract: 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.
authors: Department of Medicine, The Royal Melbourne Hospital, The University of Melbourne, Parkville, VIC, Australia.
authors: Sandy R
authors: SR
authors: Shultz
authors: Department of Medicine, The Royal Melbourne Hospital, The University of Melbourne, Parkville, VIC, Australia.
authors: Mujun
authors: M
authors: Sun
authors: 1] Anatomy and Neuroscience, The University of Melbourne, Parkville, VIC, Australia [2] The Florey Institute of Neuroscience and Mental Health, Parkville, VIC, Australia.
authors: David K
authors: DK
authors: Wright
authors: Department of Physiology, Anatomy and Microbiology, La Trobe University, Melbourne, VIC, Australia.
authors: Rhys D
authors: RD
authors: Brady
authors: Department of Medicine, The Royal Melbourne Hospital, The University of Melbourne, Parkville, VIC, Australia.
authors: Shijie
authors: S
authors: Liu
authors: Department of Medicine, The Royal Melbourne Hospital, The University of Melbourne, Parkville, VIC, Australia.
authors: Sinead
authors: S
authors: Beynon
authors: Department of Physiology, Anatomy and Microbiology, La Trobe University, Melbourne, VIC, Australia.
authors: Shannon F
authors: SF
authors: Schmidt
authors: Department of Surgery, The Royal Melbourne Hospital, The University of Melbourne, Parkville, VIC, Australia.
authors: Andrew H
authors: AH
authors: Kaye
authors: Department of Medicine, The Royal Melbourne Hospital, The University of Melbourne, Parkville, VIC, Australia.
authors: John A
authors: JA
authors: Hamilton
authors: Department of Medicine, The Royal Melbourne Hospital, The University of Melbourne, Parkville, VIC, Australia.
authors: Terence J
authors: TJ
authors: O'Brien
authors: Department of Physiology, Anatomy and Microbiology, La Trobe University, Melbourne, VIC, Australia.
authors: Brian L
authors: BL
authors: Grills
authors: Department of Physiology, Anatomy and Microbiology, La Trobe University, Melbourne, VIC, Australia.
authors: Stuart J
authors: SJ
authors: McDonald
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000000981:diagnostic imaging / Q000293:injuries; D001930:Brain Injuries / Q000150:complications / Q000000981:diagnostic imaging; D004195:Disease Models, Animal; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice; D009104:Multiple Trauma / Q000000981:diagnostic imaging*; D011859:Radiography; D013978:Tibial Fractures / Q000150:complications / Q000000981:diagnostic imaging