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Neuroinflammation is a key factor affecting patient outcomes both acutely and chronically. Traditional diagnostic tools, such as computed tomography imaging and the Glasgow Coma Scale, are limited in detecting molecular changes, particularly related to neuroinflammation. Small extracellular vesicles (sEVs) are cell\u2010specific vesicles that enable cell\u2010to\u2010cell communication and are involved in TBI pathology. In this study, brain\u2010specific sEVs are isolated by targeting brain\u2010associated markers, sodium\/potassium\u2010transporting ATPase subunit beta\u20102 (ATP1B2) and excitatory amino acid transporter 2 (EAAT2), and employed surface\u2010enhanced Raman spectroscopy to profile inflammation\u2010associated cytokine chemokine (C\u2010C motif) ligand 2 (CCL2) bound to single sEV, allowing for blood\u2010based monitoring of neuroinflammation. This approach enabled the direct assessment of neuroinflammation in both human TBI samples and a controlled cortical injury in a rat model. This study found elevated brain\u2010specific sEVs with enhanced CCL2 in TBI samples compared to non\u2010TBI cohorts. The results suggest that the TBI diagnostic platform can detect an increased level of brain\u2010specific sEVs carrying neuroinflammatory signals in TBI clinical samples with high specificity and sensitivity, offering potential as a precise diagnostic tool for TBI diagnosis.<\/jats:p>","DOI":"10.1002\/smtd.202401931","type":"journal-article","created":{"date-parts":[[2025,5,19]],"date-time":"2025-05-19T04:10:20Z","timestamp":1747627820000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Single Extracellular Vesicle Profiling to Define Brain Specific Traumatic Brain Injury Induced Neuro\u2010Inflammation"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5766-3468","authenticated-orcid":false,"given":"Zhen","family":"Zhang","sequence":"first","affiliation":[{"name":"Centre for Personalized Nanomedicine Australian Institute for Bioengineering and Nanotechnology (AIBN) The University 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