Models of lower extremity damage in mice: Time course of organ damage and immune response

Christoph L. Menzel, Roman Pfeifer, Sophie S. Darwiche, Philipp Kobbe, Roop Gill, Richard A. Shapiro, Patricia Loughran, Yoram Vodovotz, Melanie J. Scott, Mazen S. Zenati, Timothy R. Billiar, Hans Christoph Pape

Research output: Contribution to journalArticlepeer-review

27 Scopus citations


Background: Post-traumatic inflammatory changes have been identified as major causes of altered organ function and failure. Both hemorrhage and soft tissue damage induce these inflammatory changes. Exposure to heterologous bone in animal models has recently been shown to mimic this inflammatory response in a stable and reproducible fashion. This follow-up study tests the hypothesis that inflammatory responses are comparable between a novel trauma model ("pseudofracture", PFx) and a bilateral femur fracture (BFF) model. Materials and Methods: In C57BL/6 mice, markers for remote organ dysfunction and inflammatory responses were compared in four groups (control/sham/BFF/PFx) at the time points 2, 4, and 6 h. Results: Hepatocellular damage in BFF and PFx was highly comparable in extent and evolution, as shown by similar levels of NFkappaB activation and plasma ALT. Pulmonary inflammatory responses were also comparably elevated in both trauma models as early as 2 h after trauma as measured by myeloperoxidase activity (MPO). Muscle damage was provoked in both BFF and PFx mice over the time course, although BFF induced significantly higher AST and CK levels. IL-6 levels were also similar with early and sustained increases over time in both trauma models. Conclusions: Both BFF and PFx create similar reproducible inflammatory and remote organ responses. PFx will be a useful model to study longer term inflammatory effects that cannot be studied using BFF.

Original languageEnglish
Pages (from-to)e149-e156
JournalJournal of Surgical Research
Issue number2
StatePublished - Apr 2011
Externally publishedYes


  • acute lung injury
  • liver dysfunction
  • long bone fracture
  • pseudofracture
  • soft tissue injury
  • systemic inflammation


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