Speaker
Description
"Trauma is the leading global cause of mortality and disability. Patient management after trauma can be challenging, particularly in a multiple trauma setting, a condition characterized by several severe injuries. Multiple trauma can elicit major immunological responses, such as systemic inflammatory response syndrome, which lead to a deterioration in the patient’s condition. The complement system, being a central component of the immunological response after trauma, plays an important role therein. The activation of the complement system in multiple trauma, and subsequent regulation of inflammatory cascades, are therefore of clinical interest. MicroRNAs, important post-transcriptional gene regulators, may play a regulatory role in the activation and progression of immunological and regenerative responses in multiple trauma. The aim of this study was therefore to examine microRNA expression in the systemic circulation, and the sites of injury, in a porcine multiple trauma model. In this model, two different trauma treatment methods were compared, as well as one separate treatment group which was administered a combination of a C5-convertase inhibitor to inhibit complement system activation, and an anti-LPS receptor tore inhibit PAMP activation pathways.
The porcine multiple trauma model consisted of blunt chest trauma, liver laceration, bilateral femur fracture, and controlled haemorrhagic shock. Animals were operatively and medically stabilized, and monitored under ICU-standards for 72 hours, after which they were sacrificed. The control group consisted of six animals. Two trauma treatment methods were applied, early total care (ETC, n=7), and damage control orthopaedics (DCO, n=8). Furthermore, a separate group (n=4) was subjected to ETC and treated with a C5-convertase inhibitor and anti-CD14. For this study, fracture hematoma, bone from the fracture site, bone from an unfractured long bone (humerus), and blood plasma were sampled. MicroRNAs were isolated, transcribed and pooled for qPCR array analysis.
The array data revealed distinct microRNA expression levels, specific to the trauma treatment method and the application of anti-complement/anti-CD14 medication. Overall, anti-inflammatory microRNAs were upregulated in the ETC group as compared to the DCO group. The ETC group that received anti-complement/anti-CD14 medication showed a reduced expression of several of these anti-inflammatory microRNAs. In all treatment groups, the expression levels of pro-fibrotic microRNAs were lower than the expression levels of anti-fibrotic microRNAs. A major difference was observed between the fracture site samples from the ETC and DCO groups. MicroRNAs related to fibrosis were mostly downregulated in the DCO group, as compared to the upregulation of fibrotic microRNAs in the ETC group. Plasma microRNA expression revealed uniformly expressed circulating microRNAs, as well as multiple trauma specific microRNAs, and treatment specific microRNAs.
This study revealed microRNA expression profiles in fracture hematoma, bone, and plasma samples from a porcine multiple trauma model, linked to key processes in inflammation and fracture healing. Furthermore, the immunological response after multiple trauma seems to be represented in the systemic circulation through the expression of specific circulating microRNAs. Further research will focus on target analysis of the microRNA data, and in vitro fracture healing models in which mimics and antagomirs will be applied as possible regenerative and immunologic modulative therapy."
62825446719
