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

**Authors:** Marica Pagliarini, Valentina Selleri, Luana Forleo, Alice Gualerzi, Caterina Ciacci, Roberta Saltarelli, Noemi Pappagallo, Andrea Minelli, Marcello Pinti, Marzia Bedoni, Gustavo Savino, Roberta D’Alisera, Maria Cristina Albertini, Milena Nasi, Patrizia Ambrogini

PMC · DOI: 10.1007/s12035-026-05799-8 · Molecular Neurobiology · 2026-03-15

## TL;DR

This study explores neuron-derived exosomal miRNAs as potential biomarkers for detecting brain changes in amateur boxers after repeated head impacts.

## Contribution

The study identifies specific miRNAs that correlate with head trauma and could serve as non-invasive biomarkers for neuroinflammation and neuroplasticity.

## Key findings

- Sparring caused significant changes in miRNA levels linked to neuroinflammation and neuroplasticity.
- miR-146a expression correlated with the number of head impacts, suggesting its role as a sensitive marker of neuronal stress.
- Bioinformatic analysis showed miRNA target genes are enriched in pathways related to neurogenesis and synaptic remodeling.

## Abstract

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.

The online version contains supplementary material available at 10.1007/s12035-026-05799-8.

## Full-text entities

- **Genes:** IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, MIR124-1 (microRNA 124-1) [NCBI Gene 406907] {aka MIR124A, MIR124A1, MIRN124-1, MIRN124A1, mir-124-1}, CEL (carboxyl ester lipase) [NCBI Gene 1056] {aka BAL, BSDL, BSSL, CELL, CEase, FAP}, NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}, F2 (coagulation factor II, thrombin) [NCBI Gene 2147] {aka PT, RPRGL2, THPH1}, RBFOX3 (RNA binding fox-1 homolog 3) [NCBI Gene 146713] {aka FOX-3, FOX3, HRNBP3, NEUN}, MIR146B (microRNA 146b) [NCBI Gene 574447] {aka MIRN146B, miRNA146B, mir-146b}, MIR132 (microRNA 132) [NCBI Gene 406921] {aka MIRN132, miRNA132, mir-132}, MIR146A (microRNA 146a) [NCBI Gene 406938] {aka MIRN146, MIRN146A, miR-146a, miRNA146A}, DCX (doublecortin) [NCBI Gene 1641] {aka DBCN, DC, LISX, SCLH, XLIS}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, L1CAM (L1 cell adhesion molecule) [NCBI Gene 3897] {aka CAML1, CD171, HSAS, HSAS1, HYCX, MASA}, NLRP3 (NLR family pyrin domain containing 3) [NCBI Gene 114548] {aka AGTAVPRL, AII, AVP, C1orf7, CIAS1, CLR1.1}, MIR126 (microRNA 126) [NCBI Gene 406913] {aka MIRN126, miRNA126, mir-126}, GRIN2B (glutamate ionotropic receptor NMDA type subunit 2B) [NCBI Gene 2904] {aka DEE27, EIEE27, GluN2B, MRD6, NMDAR2B, NR2B}, CD63 (CD63 molecule) [NCBI Gene 967] {aka AD1, HOP-26, ME491, MLA1, OMA81H, Pltgp40}, GRIA2 (glutamate ionotropic receptor AMPA type subunit 2) [NCBI Gene 2891] {aka GLUR2, GLURB, GluA2, GluR-K2, HBGR2, NEDLIB}, MIR34A (microRNA 34a) [NCBI Gene 407040] {aka MIRN34A, miRNA34A, mir-34, mir-34a}, MIR223 (microRNA 223) [NCBI Gene 407008] {aka MIRN223, miRNA223, mir-223}, IL1B (interleukin 1 beta) [NCBI Gene 3553] {aka IL-1, IL1-BETA, IL1F2, IL1beta}
- **Diseases:** vascular compromise (MESH:D057772), depressive disorder (MESH:D003866), brain injury (MESH:D001930), trauma (MESH:D014947), neurodevelopmental disorders (MESH:D002658), ischemic stroke (MESH:D002544), vascular dysregulation (MESH:D021081), concussion (MESH:D001924), NDEs (MESH:C536408), axonal injury (MESH:D001480), major (MESH:D004830), neurodegenerative (MESH:D019636), central nervous system disorders (MESH:D002493), chronic traumatic encephalopathy (MESH:D000070627), impaired neurogenesis (MESH:D001750), vascular impairment (MESH:D020141), impacts (MESH:D004834), cerebral injury (MESH:D000070625), head impacts (MESH:D006258), Neuroinflammation (MESH:D000090862), cognitive and behavioral impairments (MESH:D003072), Parkinson's disease (MESH:D010300), neurodevelopmental syndromes (MESH:D008607), brain function and dysfunction (MESH:D001927), PCS (MESH:D038223), inflammation (MESH:D007249), major depressive disorder (MESH:D003865), TBI (MESH:D000070642), excitotoxic neuronal injury (MESH:D009410), Head Trauma (MESH:D006259), Alzheimer's disease (MESH:D000544), neurological consequences (MESH:D009461)
- **Chemicals:** Mini (-), agarose (MESH:D012685), calcium (MESH:D002118), lipids (MESH:D008055), EDTA (MESH:D004492), SDS (MESH:D012967), spike (MESH:C010346), PBS (MESH:D007854), glycine (MESH:D005998), Laemmli buffer (MESH:C088816), Tween-20 (MESH:D011136), HCl (MESH:D006851)
- **Species:** Mus musculus (house mouse, species) [taxon 10090], Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

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## References

7 references — full list in the complete paper: https://tomesphere.com/paper/PMC12989019/full.md

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Source: https://tomesphere.com/paper/PMC12989019