Pisani Anna, Rolesi Rolando, Mohamed-Hizam Veronica, Montuoro Raffaele, Paludetti Gaetano, Giorgio Cristina, Cocchiaro Pasquale, Brandolini Laura, Detta Nicola, Sirico Anna, Amendola Pier Giorgio, Novelli Rubina, Aramini Andrea, Allegretti Marcello, Paciello Fabiola, Grassi Claudio, Fetoni Anna Rita
Department of Neuroscience, Unit of Audiology, Università degli Studi di Napoli Federico II, Naples, Italy.
Department of Head and Neck Surgery, Università Cattolica del Sacro Cuore, Rome, Italy.
Br J Pharmacol. 2025 Feb;182(3):546-563. doi: 10.1111/bph.17359. Epub 2024 Oct 10.
Cisplatin-induced sensorineural hearing loss is a significant clinical challenge. Although the potential effects of brain-derived neurotrophic factor (BDNF) have previously been investigated in some ototoxicity models, its efficacy in cisplatin-induced hearing loss remains uncertain. This study aimed to investigate the therapeutic potential of recombinant human BDNF (rhBDNF) in protecting cells against cisplatin-induced ototoxicity.
Using an in vivo model of cisplatin-induced 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.
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-induced cell death. Specifically, rhBDNF maintains the balance of its receptor levels (pTrkB and p75), boosting TrkB-CREB pro-survival signalling and reducing caspase 3-dependent apoptosis in the cochlea. Additionally, it activates antioxidant mechanisms while inhibiting inflammation and promoting vascular repair.
Collectively, we demonstrated that early transtympanic treatment with rhBDNF plays a multifaceted protective role against cisplatin-induced ototoxicity, thus holding promise as a novel potential approach to preserve hearing in adult and paediatric patients undergoing cisplatin-based chemotherapy.
