Project Details
Projekt
Influence and Role of Extracellular Vesicles and their Cargo in Neuroinflammatory Processes following Polytrauma with Traumatic Brain Injury
Subject Area
Orthopaedics, Traumatology, Reconstructive Surgery
Term
since 2022
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 465409392
Polytrauma (PT) is a leading cause of death and disability in individuals under 45 years, often involving traumatic brain injury (TBI), a critical determinant of outcomes. Secondary brain injury – driven by post-traumatic neuroinflammation and blood-brain barrier (BBB) dysfunction—remains the major clinical challenge to reduce mortality. TBI-induced systemic immune dysregulation can exacerbate complications such as multiple organ failure and infections and vice versa. Traditional diagnostic tools (e.g. Glasgow Coma Scale, Computed tomography) offer limited prognostic value, especially in PT patients requiring ventilation. Current protein-based biomarkers (e.g. S100B, NSE, GFAP) are nonspecific in polytrauma setting due to extracerebral injuries and systemic inflammation. Emerging evidence highlights the diagnostic and mechanistic potential of extracellular vesicles (EVs) – small particles secreted by cells with a lipid bilayer that transport informative miRNAs, proteins, and surface markers. EVs cross the BBB, reflect injury-specific cellular activity, and participate in immune modulation. In the first founding period, we demonstrated specifically altered EV surface profiles (oligodendrocyte MBP+, microglial CD13+) and miRNA cargo (e.g. miR-423-3p, miR-338-3p) in TBI vs. PT patients that correlate with clinical findings (e.g. GCS) and systemic cytokines (e.g. IL-6). These findings position EVs not only as biomarkers but also as active mediators of injury progression. We hypothesize that BD-EVs and their miRNA cargo dynamically regulate post-traumatic neuroinflammation and secondary injury. Our work program is a direct continuation of our research made in first funding period (FOR 5714) in an in vivo mouse model. For this purpose, we will employ mono- (only TBI) and polytrauma mouse models (thoracic trauma + femur fracture + TBI). The work program is divided into four work packages in which partly in vivo (WP1 and 3) and in vitro (WP2) experiments are performed with in vivo derived murine EVs. We characterize time-dependent EV changes post-TBI (WP1), analyze BD-EV effects on BBB and immune cells in vitro (WP2), assess systemic EVs’ impact on BBB and brain inflammation in vivo (WP3), and validate findings in human samples and perfume clinical correlation with TBI database ([TBI-DB], WP4). The TBI-DB of the German Trauma Registry DGU® enables high-quality clinical correlation of molecular markers. With >800 cases, it provides longitudinal data on injury patterns, outcomes (GOSe), therapies and follow-up data (6- and 12 months). Notably, falls in the elderly represent a growing TBI cohort with significant morbidity and mortality. Integration of EV analyses with TBI-DB opens novel translational opportunities. Together, this project aims to define the pathophysiological and diagnostic role of EVs in PT with TBI and provide a foundation for future EV-based therapeutic interventions.
DFG Programme
Research Units
