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Exogenous BDNF Rescues Rat Spiral Ganglion Neurons In Vivo

McGuinness, Sarah L*; Shepherd, Robert K*†

doi: 10.1097/01.mao.0000185063.20081.50
Basic Science
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Objective: To determine if exogenous neurotrophins can prevent spiral ganglion neuron degeneration in the rat cochlea.

Background: The loss of hair cells resulting in sensorineural hearing loss also leads to the secondary degeneration of spiral ganglion neurons. The effectiveness of cochlear implantation in patients with profound sensorineural hearing loss relies in part on the survival of spiral ganglion neurons; therefore, any therapy that can prevent or halt the loss of these neurons would be of potential clinical benefit. Previous research has shown that intracochlear infusion with neurotrophins can provide trophic support to SGNs in deafened guinea pigs. Whether this effect is seen in other species remains to be determined.

Methods: After documenting the rate of spiral ganglion neuron degeneration after ototoxic deafening, we investigated the trophic effects of exogenous brain-derived neurotrophic factor (BDNF) on rat spiral ganglion neurons. The left cochleae of profoundly deafened rats were implanted with a drug delivery system connected to a mini-osmotic pump. BDNF or artificial perilymph was infused for 28 days; then the cochleae were prepared for histological study.

Results: Treatment with BDNF led to a statistically significant increase in spiral ganglion neuron density and a highly significant increase in spiral ganglion neuron soma area compared with artificial perilymph-treated and untreated deafened cochleae.

Conclusion: The study has demonstrated the trophic advantage of exogenous BDNF in the mature rat cochlea and provides confidence that spiral ganglion neuron rescue after sensorineural hearing loss with exogenous BDNF may have clinical application.

*Department of Otolaryngology, University of Melbourne, and †The Bionic Ear Institute, East Melbourne, Victoria, Australia

Address correspondence and reprint requests to R. K. Shepherd, Department of Otolaryngology, The Bionic Ear Institute, 32 Gisborne Street, East Melbourne, Victoria 3002, Australia; E-mail: rshepherd@bionicear.org

Supported by the National Institutes of Health through the NIDCD (grant NO1-DC-3-1005) and by the Faculty of Medicine, The University of Melbourne.

© 2005 Otology & Neurotology, Inc.