Interaction between posttraumatic inflammatory response in polytrauma patients with and without traumatic brain injury at the posttranscriptional level (miRNA)

• Applicant: Dr. Cora Schindler
• Subject Area: Orthopaedics, Traumatology, Reconstructive Surgery
• Term: since 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 465409392

Polytrauma (PT) and severe traumatic brain injury (TBI) caused by accidents and falls are the main causes of death and disability in young patients under 45 years with immense socioeconomic impact through loss of productivity, medical and rehabilitation costs. The brain is vulnerable to secondary damage and failure due to its high metabolic rate and limited intrinsic energy reserve. Detecting the severity of TBI at an early stage, predicting its development, and preventing secondary damage, are of highest clinical interest. microRNAs (miRNA) are small non-coding RNAs and can be assigned to specific tissues and localizations depending on their function and target sequences, making it worthwhile to investigate their potential as biomarkers for different pathological situations. miRNAs represent a significant proportion of the Extracellular Vesicles (EVs) cargo that can be released into the circulation after multiple trauma with TBI involvement. The correlation of new molecular biomarkers with the demographic and clinical data is essential for the clinical integration of experimental findings “from bench to bedside”.The aim of this 4-years prospective observational study is the identification of TBI-specific plasma EV and miRNA pattern as early markers for primary brain injury and late markers of secondary brain injury. First the identification of putative biomarkers will be performed in isolated TBI and Ctrl group samples by mean of miRNAs deep sequencing analysis (timepoints 0, 48 hrs.). Then, 10 of the identified miRNAs with the highest expression differences would be verified for TBI specificity on sub-cohorts of samples, where the group of polytrauma patients without TBI will serve to control the specificity and the group of healthy volunteers will serve as a negative reference. The most promising miRNAs would be verified on a broad number of patients from NTF biobank (timepoints 0, 24 and 48 hrs.) using RT-qPCR technique. The identification of specific TBI-related miRNAs in dependency of age and gender might provide an additional powerful decision tool to improve therapeutic intervention. In respect to find an influence of gender on immune regulation after polytrauma and the release of specific markers the project aims to analyze samples from female and male probands equally. In comparison, Project U-2 measures protein-based TBI markers (S-100, NSE) in the same samples. The role of the identified miRNAs in a larger cohort of trauma patients can be analyzed thereby using samples from the biobank which is established in C-P and F-C project. Experimental research will be performed in close methodological exchange between both projects to establish a method platform for EV isolation and preservation. The collaboration with E-1 aims to uncover possible associations at miRNA level and eventually protein level between TBI and impaired cardiac function after trauma.

• DFG Programme: Research Units
• Subproject of: FOR 5417: Translational Polytrauma Research to Provide Diagnostic and Therapeutic Tools for Improving Outcomes
• Co-Investigator: Professor Dirk Henrich, Ph.D.