Exploring Neuronal Exosome miRNAs as Biomarkers of Neuroinflammation and Neuroplasticity in Amateur Boxers After Repetitive Head Trauma

Repetitive mild traumatic brain injuries, common in contact sports like boxing, are recognized risk factors for long-term neurodegenerative conditions. There remains a clinical need for reliable, non-invasive biomarkers capable of detecting early brain alterations induced by repeated head trauma. This study evaluated the potential of neuron-derived exosomal microRNAs (miRNAs) as indicators of neuroinflammatory and neuroplastic changes in amateur boxers exposed to recurrent mild head impacts. Head impacts were measured across three weekly sparring sessions in ten male athletes. Neuron-derived exosomes were isolated from plasma samples collected both before (T0) and after (T2) the sparring period. The expression of eight miRNAs implicated in neuroplasticity and inflammation (miR-34a, miR-9, miR-124a, miR-223, miR-132, miR-126, miR-146a, and miR-146b) was analyzed using RT-qPCR. Sparring elicited a marked decrease in miR-126 levels and a significant increase in miR-34a, miR-132, miR-223, miR-146a, and miR-146b, suggesting a coordinated molecular response involving neuroinflammatory signaling, vascular dysregulation, and altered neuroplastic processes. Notably, the number of recorded head impacts correlated positively with miR-146a expression, supporting its potential role as a sensitive marker of neuronal stress. Bioinformatic analysis of miRNA target genes revealed enrichment in pathways associated with neurogenesis, axonal repair, synaptic remodeling, and brain-region-specific expression patterns characteristic of neural stem cells. Together, these findings support the potential use of neuron-derived exosomal miRNAs as peripheral biomarkers for early detection of sports-related brain injury, offering mechanistic insight into subclinical neural adaptations induced by repeated head trauma. Their implementation may contribute to minimally invasive monitoring strategies for athletes at risk.