{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T21:11:31Z","timestamp":1790975491769,"version":"4.1.0"},"reference-count":18,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,9,19]],"date-time":"2025-09-19T00:00:00Z","timestamp":1758240000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Proteomes"],"abstract":"<jats:p>Neurogranin (NRGN), a synaptic protein essential for plasticity and memory function, is gaining recognition as a promising biomarker for mild traumatic brain injury (mTBI). This systematic review brings together findings from six studies that measured neurogranin levels in biofluids\u2014including serum, cerebrospinal fluid (CSF), plasma, and exosomes\u2014during both the acute and chronic phases following injury. In the acute phase of mTBI, elevated levels of neurogranin were consistently observed in serum samples, suggesting its potential as a diagnostic marker. These increases appear to reflect immediate synaptic disturbances caused by injury. In contrast, studies focusing on the chronic phase reported a decrease in exosomal neurogranin levels, pointing to ongoing synaptic dysfunction well after the initial trauma. This temporal shift in neurogranin expression highlights its dual utility\u2014both as an early indicator of injury and as a longer-term marker of synaptic integrity. However, interpreting these findings is not straightforward. The studies varied considerably in terms of sample type, timing of measurements, and control for potential confounding factors such as physical activity. Such variability makes direct comparisons difficult and may influence the outcomes observed. Additionally, none of the studies included proteoform-specific analyses of neurogranin, an omission that limits our understanding of the molecular changes underlying mTBI-related synaptic alterations. Due to heterogeneity across study designs and outcome measures, a meta-analysis could not be performed. Instead, a narrative synthesis was conducted, revealing consistent patterns in neurogranin dynamics over time and underscoring the influence of biofluid selection on measured outcomes. Overall, the current evidence supports neurogranin\u2019s potential as both a diagnostic and mechanistic biomarker for mTBI. Yet, to fully realize its clinical utility, future research must prioritize standardized protocols, the inclusion of proteoform profiling, and rigorous longitudinal validation studies.<\/jats:p>","DOI":"10.3390\/proteomes13030046","type":"journal-article","created":{"date-parts":[[2025,9,19]],"date-time":"2025-09-19T08:11:01Z","timestamp":1758269461000},"page":"46","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Neurogranin as a Synaptic Biomarker in Mild Traumatic Brain Injury: A Systematic Review of Diagnostic and Pathophysiological Evidence"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9844-4010","authenticated-orcid":false,"given":"Ioannis","family":"Mavroudis","sequence":"first","affiliation":[{"name":"Department of Neuroscience, Leeds Teaching Hospitals, NHS Trust, Leeds LS1 3EX, UK"},{"name":"Department of Neurosciences, University of Leeds, Leeds LS2 9JT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5617-0346","authenticated-orcid":false,"given":"Foivos","family":"Petridis","sequence":"additional","affiliation":[{"name":"Third Department of Neurology, Aristotle University of Thessaloniki, 57010 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1941-0432","authenticated-orcid":false,"given":"Eleni","family":"Karantali","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Alexandroupolis, 69100 Alexandroupoli, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7319-2045","authenticated-orcid":false,"given":"Dimitrios","family":"Kazis","sequence":"additional","affiliation":[{"name":"Third Department of Neurology, Aristotle University of Thessaloniki, 57010 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"838","DOI":"10.1136\/bjsports-2017-097699","article-title":"Consensus statement on concussion in sport\u2014The 5th international conference on concussion in sport held in Berlin, October 2016","volume":"51","author":"McCrory","year":"2017","journal-title":"Br. 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