{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T02:28:08Z","timestamp":1786328888228,"version":"build-2736575974"},"reference-count":31,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2026,8,8]],"date-time":"2026-08-08T00:00:00Z","timestamp":1786147200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Background: Diffuse axonal brain injury (DABI) is a major component of traumatic brain injury, but the optimal timing of magnetic resonance imaging and histologic assessment after isolated DABI remains unclear. Because each method captures a different phase of injury, defining time-dependent diagnostic windows may improve experimental design and reduce animal use. Methods: Sixty-four Sprague-Dawley rats were randomized to moderate DABI or sham operation. Neurological Severity Score (NSS), 3 T diffusion tensor imaging (DTI), and histologic assessment were performed at early and late time points. Hippocampal fractional anisotropy (FA) was measured at 48 h and 1 month. \u03b2-amyloid precursor protein (\u03b2-APP) immunohistochemistry assessed acute axonal injury at 48 h, and hematoxylin and eosin (H&amp;E) staining quantified hippocampal neuronal density at 1 month. Results: At 48 h, DABI rats had higher NSS, lower hippocampal FA, and greater \u03b2-APP-positive axonal accumulation than sham-operated rats. By 1 month, NSS and hippocampal FA no longer differed between groups, whereas hippocampal neuronal density remained significantly reduced in DABI rats, indicating persistent structural injury. Conclusions: In this rat model of isolated DABI, hippocampal FA and \u03b2-APP immunohistochemistry identified acute axonal pathology at 48 h, whereas conventional histology detected a persistent reduction in neuronal density at 1 month. These findings support a time-optimized diagnostic strategy using early DTI for noninvasive injury detection and late histology for long-term structural assessment.<\/jats:p>","DOI":"10.3390\/diagnostics16162503","type":"journal-article","created":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T01:20:03Z","timestamp":1786324803000},"page":"2503","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Time-Dependent Diagnostic Windows After Isolated Diffuse Axonal Brain Injury in Rats"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7548-3946","authenticated-orcid":false,"given":"Vladislav","family":"Zvenigorodsky","sequence":"first","affiliation":[{"name":"Department of Radiology, Soroka University Medical Center and the Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva 84101, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3120-5709","authenticated-orcid":false,"given":"Benjamin F.","family":"Gruenbaum","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Jacksonville, FL 32224, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8398-6455","authenticated-orcid":false,"given":"Ilan","family":"Shelef","sequence":"additional","affiliation":[{"name":"Department of Radiology, Soroka University Medical Center and the Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva 84101, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8604-2348","authenticated-orcid":false,"given":"Dmitry","family":"Frank","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Critical Care, Soroka University Medical Center, Ben-Gurion University of the Negev, Beer-Sheva 84101, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatris","family":"Tsafarov","sequence":"additional","affiliation":[{"name":"Department of Histology, Soroka University Medical Center and the Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva 84101, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shahar","family":"Negev","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Critical Care, Soroka University Medical Center, Ben-Gurion University of the Negev, Beer-Sheva 84101, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuly","family":"Doviner","sequence":"additional","affiliation":[{"name":"Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva 84101, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4162-8406","authenticated-orcid":false,"given":"Amit","family":"Frenkel","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Critical Care, Soroka University Medical Center, Ben-Gurion University of the Negev, Beer-Sheva 84101, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Dubilet","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Critical Care, Soroka University Medical Center, Ben-Gurion University of the Negev, Beer-Sheva 84101, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Zlotnik","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Critical Care, Soroka University Medical Center, Ben-Gurion University of the Negev, Beer-Sheva 84101, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3116-1643","authenticated-orcid":false,"given":"Matthew","family":"Boyko","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Critical Care, Soroka University Medical Center, Ben-Gurion University of the Negev, Beer-Sheva 84101, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1038\/nrneurol.2013.22","article-title":"Changing patterns in the epidemiology of traumatic brain injury","volume":"9","author":"Roozenbeek","year":"2013","journal-title":"Nat. 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