{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T05:07:30Z","timestamp":1779944850427,"version":"3.53.1"},"reference-count":29,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T00:00:00Z","timestamp":1779926400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000005","name":"Department of Defense","doi-asserted-by":"publisher","award":["RH220046"],"award-info":[{"award-number":["RH220046"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:p>Blast-induced hearing loss (BIHL) is a prevalent form of sensory neurotrauma resulting from military and occupational blast exposure. However, effective post-injury interventions remain limited, and progress is hindered by challenges in delivering therapeutics to the injured cochlea. In this study, we developed a reproducible compressed-air blast mouse model with quantified output characteristics and evaluated a localized post-blast TrkB activation strategy using 7,8-dihydroxyflavone (7,8-DHF) delivered to the cochlea via poly(lactide-co-glycolide)-graft-polyethylenimine (PgP) nanoparticles. Device characterization demonstrated a monotonic relationship between regulator-setting pressure (100\u2013250\u202fpsi) and acoustic output (72\u2013124\u202fdB). In addition, device modification increased acoustic output while reducing peak pressure relative to the prior configuration, thereby enabling reproducible, pressure-dependent injury. A single unilateral blast exposure produced robust elevations in auditory brainstem response (ABR) thresholds that partially recovered at intermediate regulator settings; however, these thresholds remained elevated over time at higher regulator settings. Since the modified blast paradigm frequently produced tympanic membrane perforation, we leveraged this transient access route to deliver 7,8-DHF-loaded nanoparticles through the ear canal immediately after blast. Compared with vehicle treatment, local 7,8-DHF delivery accelerated functional recovery and yielded significantly improved ABR thresholds, whereas vehicle-treated mice remained persistently impaired at 1\u202fmonth. Histological analyses revealed preserved inner hair cell density, but significant outer hair cell loss and reduced inner hair cell ribbon synapses in mice exposed to blast. 7,8-DHF-loaded PgP attenuated outer hair cell loss and partially preserved ribbon synapses, with the strongest protection in basal cochlear regions. Together, these findings provide an accessible BIHL platform and support nanoparticle-enabled local TrkB activation as a feasible post-blast strategy that improves both functional and structural endpoints relevant to sensory neurotrauma.<\/jats:p>","DOI":"10.3389\/fneur.2026.1822487","type":"journal-article","created":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T04:58:53Z","timestamp":1779944333000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["TrkB activation mitigates blast-induced cochlear pathology and promotes auditory recovery in a compressed-air blast model"],"prefix":"10.3389","volume":"17","author":[{"given":"Han-Gyu","family":"Bae","sequence":"first","affiliation":[{"name":"Kresge Hearing Research Institute, Department of Otolaryngology-Head and Neck Surgery, University of Michigan","place":["Ann Arbor, MI, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sung Kyun","family":"Kim","sequence":"additional","affiliation":[{"name":"Kresge Hearing Research Institute, Department of Otolaryngology-Head and Neck Surgery, University of Michigan","place":["Ann Arbor, MI, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashley","family":"Park","sequence":"additional","affiliation":[{"name":"Kresge Hearing Research Institute, Department of Otolaryngology-Head and Neck Surgery, University of Michigan","place":["Ann Arbor, MI, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex","family":"Vandenberg","sequence":"additional","affiliation":[{"name":"Drug Design Development Delivery (4D) Laboratory, Department of Bioengineering, Clemson University","place":["Clemson, SC, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeoung Soo","family":"Lee","sequence":"additional","affiliation":[{"name":"Drug Design Development Delivery (4D) Laboratory, Department of Bioengineering, Clemson University","place":["Clemson, SC, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun Hee","family":"Kim","sequence":"additional","affiliation":[{"name":"Kresge Hearing Research Institute, Department of Otolaryngology-Head and Neck Surgery, University of Michigan","place":["Ann Arbor, MI, United States"]},{"name":"Department of Cell and Developmental Biology, University of Michigan","place":["Ann Arbor, MI, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,28]]},"reference":[{"key":"ref1","volume-title":"Annual Benefits Report","year":"2025"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"e67618","DOI":"10.1371\/journal.pone.0067618","article-title":"Mechanisms of hearing loss after blast injury to the ear","volume":"8","author":"Cho","year":"2013","journal-title":"PLoS 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