Delayed neurotrophin treatment following deafness rescues spiral ganglion cells from death and promotes regrowth of auditory nerve peripheral processes: effects of brain-derived neurotrophic factor and fibroblast growth factor.
The extent to which neurotrophic factors are able to not only rescue the auditory nerve from deafferentation-induced degeneration but also promote process regrowth is of basic and clinical interest, as regrowth may enhance the therapeutic efficacy of cochlear prostheses. The use of neurotrophic factors is also relevant to interventions to promote regrowth and repair at other sites of nerve trauma. Therefore, auditory nerve survival and peripheral process regrowth were assessed in the guinea pig cochlea following chronic infusion of BDNF + FGF(1) into scala tympani, with treatment initiated 4 days, 3 weeks, or 6 weeks after deafferentation from deafening. Survival of auditory nerve somata (spiral ganglion neurons) was assessed from midmodiolar sections. Peripheral process regrowth was assessed using pan-Trk immunostaining to selectively label afferent fibers. Significantly enhanced survival was seen in each of the treatment groups compared to controls receiving artificial perilymph. A large increase in peripheral processes was found with BDNF + FGF(1) treatment after a 3-week delay compared to the artificial perilymph controls and a smaller enhancement after a 6-week delay. Neurotrophic factor treatment therefore has the potential to improve the benefits of cochlear implants by maintaining a larger excitable population of neurons and inducing neural regrowth.
Miller
Josef M
JM
Kresge Hearing Research Institute, University of Michigan, Ann Arbor, Michigan 48109-0506, USA. Josef@umich.edu
Le Prell
Colleen G
CG
Prieskorn
Diane M
DM
Wys
Noel L
NL
Altschuler
Richard A
RA
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000627:therapeutic use*; D002452:Cell Count; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003051:Cochlea / Q000502:physiology; D003056:Cochlear Nerve / Q000187:drug effects* / Q000473:pathology*; D003638:Deafness / Q000188:drug therapy* / Q000473:pathology*; D005260:Female; D005346:Fibroblast Growth Factors / Q000627:therapeutic use*; D006168:Guinea Pigs; D008297:Male; D008845:Microinjections; D009412:Nerve Fibers / Q000502:physiology; D009414:Nerve Growth Factors / Q000627:therapeutic use*; D009475:Neurons, Afferent / Q000473:pathology; D020917:Receptor, trkA / Q000378:metabolism; D013136:Spiral Ganglion / Q000187:drug effects* / Q000473:pathology*
D019208:Brain-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D005346:Fibroblast Growth Factors; D020917:Receptor, trkA