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. 2012:2012:890816.
doi: 10.1155/2012/890816. Epub 2012 Feb 29.

A new experimental polytrauma model in rats: molecular characterization of the early inflammatory response

Sebastian Weckbach  1 , Mario Perl, Tim Heiland, Sonja Braumüller, Philip F Stahel, Michael A Flierl, Anita Ignatius, Florian Gebhard, Markus Huber-Lang
Affiliations

A new experimental polytrauma model in rats: molecular characterization of the early inflammatory response

Sebastian Weckbach et al. Mediators Inflamm. 2012.

Abstract

Background: The molecular mechanisms of the immune response after polytrauma are highly complex and far from fully understood. In this paper, we characterize a new standardized polytrauma model in rats based on the early molecular inflammatory and apoptotic response.

Methods: Male Wistar rats (250 g, 6-10/group) were anesthetized and exposed to chest trauma (ChT), closed head injury (CHI), or Tib/Fib fracture including a soft tissue trauma (Fx + STT) or to the following combination of injuries: (1) ChT; (2) ChT + Fx + STT; (3) ChT + CHI; (4) CHI; (5) polytrauma (PT = ChT + CHI + Fx + STT). Sham-operated rats served as negative controls. The inflammatory response was quantified at 2 hours and 4 hours after trauma by analysis of "key" inflammatory mediators, including selected cytokines and complement components, in serum and bronchoalveolar (BAL) fluid samples.

Results: Polytraumatized (PT) rats showed a significant systemic and intrapulmonary release of cytokines, chemokines, and complement anaphylatoxins, compared to rats with isolated injuries or selected combinations of injuries.

Conclusion: This new rat model appears to closely mimic the early immunological response of polytrauma observed in humans and may provide a valid basis for evaluation of the complex pathophysiology and future therapeutic immune modulatory approaches in experimental polytrauma.

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Figures

Figure 1
Figure 1
Systemic inflammatory response following trauma, (a) shows the systemic IL-6 (pg/mL) serum levels in Sham versus PT animals 2 and 4 hrs after trauma, (b) the CINC (pg/mL) serum concentrations in Sham versus PT animals 2 and 4 hrs after trauma and (c) the TNF-α (pg/mL) serum levels in Sham versus PT animals 2 and 4 hrs after trauma. All data are presented as mean ± SD. *P < 0.05. n = 6–10 rats/group.
Figure 2
Figure 2
Local inflammatory response following trauma, (a) shows IL-6 (ng/mL) BAL-Fluid levels in Sham-, ChT-, ChT + Fx + STT-, ChT + CHI-, CHI- and PT-rats 4 hrs after trauma, (b) TNF-α (ng/mL) BAL-Fluid levels in Sham-, ChT-, ChT + Fx + STT-, ChT + CHI-, CHI- and PT-rats 4 hrs post trauma, (c) CINC (pg/mL) BAL-Fluid concentrations in Sham-, ChT-, ChT + Fx + STT-, ChT + CHI-, CHI- and PT-rats 4 hrs after trauma and (d) MCP-1 BAL-Fluid levels in Sham-, ChT-, ChT + Fx + STT-, ChT + CHI-, CHI- and PT-rats 4 hrs after trauma. All data are presented as mean ± SD. *P < 0.05 to Sham; # P < 0.05 significant to CHT. n = 6–10 rats/group.
Figure 3
Figure 3
Histological changes in lung tissues after trauma, H&E stained lung tissue sections of Sham-, ChT-, CHI and PT-rats analysed by light microscopy with 20x amplification.
Figure 4
Figure 4
Systemic complement response after trauma, (a) presents the hemolytic activity (CH50/mg) on Sham- and PT-rats 2 and 4 hrs after trauma, (b) the C3a (ng/mL) BAL-Fluid levels in Sham- versus PT-rats 2 and 4 hrs post trauma and (c) the C3aR Expression (MFI) on Monocytes, Neutrophils and Lymphocytes in Sham- and PT-rats 4 hrs after trauma. All data are presented as mean ± SD. *P < 0.05. n = 6–10 rats/group.
Figure 5
Figure 5
Complement regulatory response after trauma, CReg Expression (MFI) CD59, CD35 and CD55 on neutrophils (PMNs) in Sham- and PT rats 4 hrs after trauma. All data are presented as mean ± SD. *P < 0.05. n = 6–10 rats/group.
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