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Although the potential effects of brain\u2010derived neurotrophic factor (BDNF) have previously been investigated in some ototoxicity models, its efficacy in cisplatin\u2010induced hearing loss remains uncertain. This study aimed to investigate the therapeutic potential of recombinant human BDNF (rhBDNF) in protecting cells against cisplatin\u2010induced ototoxicity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental Approach<\/jats:title>\n                    <jats:p>\n                      Using an\n                      <jats:italic>in vivo<\/jats:italic>\n                      model of cisplatin\u2010induced hearing loss, we investigated the beneficial effects of transtympanic administration of rhBDNF in a thermogel solution on hearing function and cochlear injury, using electrophysiological, morphological, immunofluorescence and molecular analyses.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>Our data showed that local rhBDNF treatment counteracted hearing loss in rats receiving cisplatin by preserving synaptic connections in the cochlear epithelium and protecting hair cells (HCs) and spiral ganglion neurons (SGNs) against cisplatin\u2010induced cell death. Specifically, rhBDNF maintains the balance of its receptor levels (pTrkB and p75), boosting TrkB\u2010CREB pro\u2010survival signalling and reducing caspase 3\u2010dependent apoptosis in the cochlea. Additionally, it activates antioxidant mechanisms while inhibiting inflammation and promoting vascular repair.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion and Implications<\/jats:title>\n                    <jats:p>Collectively, we demonstrated that early transtympanic treatment with rhBDNF plays a multifaceted protective role against cisplatin\u2010induced ototoxicity, thus holding promise as a novel potential approach to preserve hearing in adult and paediatric patients undergoing cisplatin\u2010based chemotherapy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.17359","type":"journal-article","created":{"date-parts":[[2024,10,10]],"date-time":"2024-10-10T23:54:57Z","timestamp":1728604497000},"page":"546-563","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Early transtympanic administration of rhBDNF exerts a multifaceted neuroprotective effect against cisplatin\u2010induced hearing loss"],"prefix":"10.1111","volume":"182","author":[{"given":"Anna","family":"Pisani","sequence":"first","affiliation":[{"name":"Department of Neuroscience, Unit of Audiology Universit\u00e0 degli Studi di Napoli Federico II  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rolando","family":"Rolesi","sequence":"additional","affiliation":[{"name":"Department of Head and Neck Surgery Universit\u00e0 Cattolica del Sacro Cuore  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronica","family":"Mohamed\u2010Hizam","sequence":"additional","affiliation":[{"name":"Department of Head and Neck Surgery Universit\u00e0 Cattolica del Sacro Cuore  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raffaele","family":"Montuoro","sequence":"additional","affiliation":[{"name":"Department of Head and Neck Surgery Universit\u00e0 Cattolica del Sacro Cuore  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaetano","family":"Paludetti","sequence":"additional","affiliation":[{"name":"Department of Head and Neck Surgery Universit\u00e0 Cattolica del Sacro Cuore  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Giorgio","sequence":"additional","affiliation":[{"name":"Research &amp; Early Development Domp\u00e9 Farmaceutici S.p.A.  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