Otol Neurotol 26(5): 1064-1072

Exogenous BDNF rescues rat spiral ganglion neurons <em>in vivo</em>

^{Department of Otolaryngology, The University of Melbourne, 32 Gisborne Street, East Melbourne, Victoria 3002, Australia}

^{The Bionic Ear Institute, 384-388 Albert St, East Melbourne, Victoria 3002, Australia}

^{Correspondence to: Dr R.K. Shepherd The Bionic Ear Institute, Department of Otolaryngology 32 Gisborne Street, East Melbourne, Victoria 3002, Australia Phone: + 61 3 99298397; Fax: 96631958 e-mail:}gro.raecinoib@drehpehsr

Abstract

The loss of hair cells resulting in a sensorineural hearing loss (SNHL) also leads to the secondary degeneration of spiral ganglion neurons (SGNs). The effectiveness of cochlear implantation in patients with a profound SNHL relies, in part, upon the survival of SGNs; 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. It remains to be determined whether this effect is seen in other species. After documenting the rate of SGN degeneration following ototoxic deafening, we investigated the trophic effects of exogenous brain-derived neurotrophic factor (BDNF) on rat SGNs. The left cochleae of profoundly deafened rats were implanted with a drug delivery system connected to a mini-osmotic pump. BDNF or artificial perilymph (AP) was infused for 28 days and the cochleae were then prepared for histology. Treatment with BDNF led to a statistically significant increase in SGN density and a highly significant increase in SGN soma area compared to AP-treated and untreated deafened cochleae. This work has demonstrated the trophic advantage of exogenous BDNF in the mature rat cochlea and provides confidence that SGN rescue following SNHL with exogenous BDNF may have clinical application.

Keywords: Neural degeneration, neurotrophin, deafness, ototoxicity, cochlear implant

Abstract

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