Resprouting and survival of guinea pig cochlear neurons in response to the administration of the neurotrophins brain-derived neurotrophic factor and neurotrophin-3

• Published in: Journal of comparative neurology (1911) 2005-06, Vol.487 (2), p.147-165
• Main Authors: Wise, Andrew K., Richardson, Rachael, Hardman, Jennifer, Clark, Graeme, O'Leary, Stephen
• Format: Article
• Language: English
• Subjects: Animals; auditory neurons; Brain-Derived Neurotrophic Factor - administration & dosage; Cell Count - methods; Cell Survival - drug effects; Cochlea - metabolism; Cochlea - pathology; Cochlear Implantation - methods; Deafness - chemically induced; Deafness - complications; Deafness - drug therapy; Disease Models, Animal; Furosemide - toxicity; GAP-43 Protein - metabolism; Guinea Pigs; Immunohistochemistry - methods; Kanamycin - toxicity; Models, Biological; Nerve Degeneration - etiology; Nerve Degeneration - metabolism; Nerve Degeneration - pathology; Nerve Degeneration - prevention & control; Nerve Regeneration - drug effects; Nerve Regeneration - physiology; neural regeneration; Neurofilament Proteins - metabolism; Neurons, Afferent - drug effects; Neurons, Afferent - metabolism; Neurons, Afferent - pathology; Neurotrophin 3 - administration & dosage; Time Factors
• ISSN: 0021-9967; 1096-9861
• DOI: 10.1002/cne.20563

Degeneration of auditory neurons occurs after deafening and is associated with damage to the organ of Corti. The administration of neurotrophins can protect auditory neurons against degeneration if given shortly after deafening. However, it is not known whether the delayed administration of neurotrophins, when significant degeneration has already occurred, will provide similar protection. Furthermore, little is known about the effects of neurotrophins on the peripheral processes of the auditory neurons or whether these neurons can resprout. This study examined the morphological effects on auditory neurons following deafening and the administration of brain‐derived neurotrophic factor and neurotrophin‐3. Results showed that neurotrophins were effective in preventing death of auditory neurons if administered 5 days after deafening and were also effective in preventing the continued loss of neurons if the administration was delayed by 33 days. The peripheral processes of auditory neurons in cochleae that received neurotrophins were in greater number and had larger diameters compared with the untreated cochleae. Localized regions of resprouting peripheral processes were observed in deafened cochleae and were enhanced in response to neurotrophin treatment, occurring across wider regions of the cochlea. These findings have significant implications for an improvement in the performance of the cochlear implant and for future therapies to restore hearing to the deaf. J. Comp. Neurol. 487:147–165, 2005. © 2005 Wiley‐Liss, Inc.