Impact of Polytrauma on the Healthy Muscle

Polytrauma is characterized by the simultaneous and life-threatening occurrence of injuries to multiple body regions, which can lead to complex systemic reactions and organ damage extending far beyond the directly injured areas. As the largest organ in the body, skeletal muscle can be affected by these systemic effects even if not directly damaged. Therefore, the aim of this study was to investigate the effects of remote organ damage after experimental polytrauma on healthy mouse skeletal muscle over a period of five days. 12-week-old male C57BL/6N mice were randomly assigned to either a polytrauma or sham group. The polytrauma model consisted of thoracic trauma, hemorrhagic shock, femur osteotomy with external fixator application, and laparotomy to simulate clinically relevant injury patterns. 1, 3 and 5 days after trauma, the indirectly affected quadriceps femoris muscle was examined from 8 – 10 animals per group. Skeletal muscle analysis was performed using light microscopy, Western blot, and quantitative real-time PCR. The collected data were statistically evaluated using two-way ANOVA in Graph Pad Prism. Histological examinations showed increased signs of muscle fiber damage in the polytrauma group, such as cell necrosis, interstitial edema formation and a decrease in fiber diameter. Gene expression analyses revealed significant upregulation of the atrogenes MuRF1 and Atrogin-1, especially on the first day after trauma induction. Additionally, increased expression of pro- and anti-inflammatory cytokines was observed, with peak values of IL-6 on day 1 and IL-10 on day 3. Interestingly, the IGF-1/PI3K/Akt signaling pathway, as measured by IR and IRS-1 expression, Akt phosphorylation, and mTOR expression, showed no significant changes between groups in Western blot analysis. This suggests that the muscle atrophy and inflammation induced by this polytrauma model occur independently of the classical insulin-mediated signaling pathway. This study demonstrates that experimental polytrauma leads to time-dependent structural and molecular changes in indirectly affected skeletal muscle. The activation of atrogenes and increased expression of inflammatory mediators seem to play a central role, while the IGF-1/PI3K/Akt signaling pathway is not significantly affected. These findings could contribute to the development of targeted therapeutic approaches to minimize muscular dysfunction and atrophy after severe trauma. Further investigations are necessary to fully elucidate the underlying mechanisms and develop potential intervention strategies.