Temporal and Severity-Dependent Alterations in Plasma Extracellular Vesicle Profiles Following Spinal Cord Injury

Spinal cord injury (SCI) triggers both local and systemic pathological responses that evolve over time and differ with injury severity. Small extracellular vesicles (sEVs), known mediators of intercellular communication, may serve as biomarkers reflecting these complex dynamics. In this study, we in...

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Bibliographic Details
Main Authors: Jamie Cooper, Scott Tait Airey, Eric Patino, Theo Andriot, Mousumi Ghosh, Damien D. Pearse
Format: Article
Language:English
Published: MDPI AG 2025-07-01
Series:Cells
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Online Access:https://www.mdpi.com/2073-4409/14/14/1065
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Summary:Spinal cord injury (SCI) triggers both local and systemic pathological responses that evolve over time and differ with injury severity. Small extracellular vesicles (sEVs), known mediators of intercellular communication, may serve as biomarkers reflecting these complex dynamics. In this study, we investigated whether SCI severity modulates the composition and abundance of circulating plasma-derived sEVs across subacute and chronic phases. Using a graded thoracic contusion model in mice, plasma was collected at defined timepoints post-injury. sEVs were isolated via size-exclusion chromatography and characterized using nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM), and MACSPlex surface marker profiling. We observed an SCI-dependent increase in sEVs during the subacute (7 days) phase, most notably in moderate injuries (50 kdyne), with overall vesicle counts lower chronically (3 months). CD9 emerged as the predominant tetraspanin sEV marker, while CD63 and CD81 were generally present at low levels across all injury severities and timepoints. Surface sEV analysis revealed dynamic regulation of CD41<sup>+</sup>, CD44<sup>+</sup>, and CD61<sup>+</sup> in the CD9<sup>+</sup> sEV subset, suggesting persistent systemic signaling activity. These markers, traditionally associated with platelet function, may also reflect immune or reparative responses following SCI. Our findings highlight the evolving nature of sEV profiles after SCI and support their potential as non-invasive biomarkers for monitoring injury progression.
ISSN:2073-4409