MiR338-3p expression in extracellular vesicles after severe trauma with or without traumatic brain injury

Polytrauma and severe traumatic brain injury (TBI) are major global health burdens associated with high morbidity and mortality, requiring accurate and early diagnosis to prevent secondary complications. In polytrauma, current protein-based biomarkers for TBI lack specificity, highlighting the need for novel approaches. Circulating microRNAs, especially those encapsulated in extracellular vesicles, represent a promising alternative due to their stability and tissue-specific signatures. This study investigates compartment-specific expression of candidate microRNAs in plasma, total extracellular vesicles and neuro-derived extracellular vesicles following trauma. In this retrospective analysis, blood samples were prospectively collected from 20 trauma patients (Injury Severity Score ≥ 16; <i>n</i> = 10 polytrauma without TBI and <i>n</i> = 10 with isolated TBI) and 10 healthy controls at two time points (≤3 and 48 h post-injury). Extracellular vesicles were isolated from plasma, and neuron-derived extracellular vesicles were enriched using L1CAM-coated magnetic beads. Expression of five microRNAs (miR-21-5p, miR-142-3p, miR-191-5p, miR-192-3p and miR-338-3p) was quantified via real-time polymerase chain reaction in plasma and in (neuron-derived) extracellular vesicles. miR-21-5p was significantly elevated in plasma shortly after polytrauma and correlated with injury severity, leukocytosis and prolonged stay on intensive care unit. In TBI patients, higher injury severity scores correlate with worse outcomes, while intracranial pressure was linked to improved recovery. miR-192-3p was predominantly enriched in neuron-derived extracellular vesicles. After polytrauma, its levels in neuron-derived extracellular vesicles were further elevated but declined after 48 h. In contrast, after TBI, miR-192-3p levels in neuron-derived extracellular vesicles initially decreased compared with healthy controls and increased again at 48 h. miR-338-3p exhibited time- and injury-dependent expression patterns. After polytrauma, it was significantly elevated in plasma and extracellular vesicles within the first hours and was associated with inflammation, organ failure and prolonged ventilation. After TBI, miR-338-3p showed a marked increase in neuron-derived extracellular vesicles at 48 h. Compartment-specific microRNA profiling reveals distinct molecular signatures after polytrauma and TBI. Increased miR-21-5p levels after polytrauma were associated with inflammation and worse clinical condition. miR-192-3p was enriched in neuron-derived extracellular vesicles in healthy controls but decreased early after TBI. miR-338-3p showed a context-dependent pattern: increased rapidly in plasma and extracellular vesicles after polytrauma but showed a delayed, TBI-specific upregulation in neuron-derived extracellular vesicles at 48 h, suggesting a potential role in CNS-specific injury or repair processes.