A new multiple trauma model of the mouse

Nadine Steubesand,Deike Varoga,Tim Klueter,Thomas Pufe,Hagen Andruszkow,Claudia Neunaber,Mersedeh Tohidnezhad,Matthias Weuster,Stefanie Fitschen-Oestern,Sebastian Lippross,Frank Hildebrand,Andreas Seekamp,Stefan Rose-John

doi:10.1186/s12891-017-1813-9

Nadine Steubesand, Deike Varoga + Show 11 more

Open Access

https://doi.org/10.1186/s12891-017-1813-9

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Abstract

BackgroundBlunt trauma is the most frequent mechanism of injury in multiple trauma, commonly resulting from road traffic collisions or falls. Two of the most frequent injuries in patients with multiple trauma are chest trauma and extremity fracture. Several trauma mouse models combine chest trauma and head injury, but no trauma mouse model to date includes the combination of long bone fractures and chest trauma. Outcome is essentially determined by the combination of these injuries. In this study, we attempted to establish a reproducible novel multiple trauma model in mice that combines blunt trauma, major injuries and simple practicability.MethodsNinety-six male C57BL/6 N mice (n = 8/group) were subjected to trauma for isolated femur fracture and a combination of femur fracture and chest injury. Serum samples of mice were obtained by heart puncture at defined time points of 0 h (hour), 6 h, 12 h, 24 h, 3 d (days), and 7 d.ResultsA tendency toward reduced weight and temperature was observed at 24 h after chest trauma and femur fracture. Blood analyses revealed a decrease in hemoglobin during the first 24 h after trauma. Some animals were killed by heart puncture immediately after chest contusion; these animals showed the most severe lung contusion and hemorrhage. The extent of structural lung injury varied in different mice but was evident in all animals. Representative H&E-stained (Haematoxylin and Eosin-stained) paraffin lung sections of mice with multiple trauma revealed hemorrhage and an inflammatory immune response. Plasma samples of mice with chest trauma and femur fracture showed an up-regulation of IL-1β (Interleukin-1β), IL-6, IL-10, IL-12p70 and TNF-α (Tumor necrosis factor- α) compared with the control group. Mice with femur fracture and chest trauma showed a significant up-regulation of IL-6 compared to group with isolated femur fracture.ConclusionsThe multiple trauma mouse model comprising chest trauma and femur fracture enables many analogies to clinical cases of multiple trauma in humans and demonstrates associated characteristic clinical and pathophysiological changes. This model is easy to perform, is economical and can be used for further research examining specific immunological questions.

Highlights

Blunt trauma is the most frequent mechanism of injury in multiple trauma, commonly resulting from road traffic collisions or falls
Several trauma mouse models focus on blunt chest trauma and head injury, but to our knowledge the Fitschen-Oestern et al BMC Musculoskeletal Disorders (2017) 18:468 combination of chest trauma and long bone fractures has not been previously emphasized
The extent of the inflammatory immune response correlates with the degree of tissue damage [4], whereas extremity fractures in particular are generally accompanied by extensive soft tissue damage in multiple trauma patients [5]

Summary

Introduction

Blunt trauma is the most frequent mechanism of injury in multiple trauma, commonly resulting from road traffic collisions or falls. The extent of the inflammatory immune response correlates with the degree of tissue damage [4], whereas extremity fractures in particular are generally accompanied by extensive soft tissue damage in multiple trauma patients [5]. Cytokines are important components of the immune response, and their release correlates with the degree of trauma depending on the extent of the associated injury [8]. Cytokines such as IL-6 serve as markers for the severity of trauma and early identification of high-risk patients for the development of posttraumatic MODS (multi organ dysfunction syndrome) [9]

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