Rescue and regrowth of sensory nerves following deafferentation by neurotrophic factors.
Trauma and loss of cochlear inner hair cells causes a series of events that result first in the retraction of the peripheral processes of the auditory nerve, scar formation in the organ of Corti, and over the course of weeks to months (depending on the species) the loss of auditory nerve cell bodies (spiral ganglion cells). Neurotrophic factors play an important role in the mature nervous system as survival factors for maintenance and protection and also can play a role in regrowth. Studies in the cochlea now show that application of exogenous neurotrophic factors can enhance survival of spiral ganglion cells after deafness and induce regrowth of peripheral processes, perhaps by replacing lost endogenous factors. Combinations of factors may be most effective for achieving greatest survival and regrowth. Our studies find that brain-derived neurotrophic factor (BDNF) and glial-line-derived neurotrophic factor (GDNF) are very effective at enhancing spiral ganglion cell survival following deafness from ototoxic drugs or noise. It has also been found that BDNF plus fibroblast growth factor (FGF) is very effective at inducing process regrowth. Electrical stimulation also acts to enhance spiral ganglion cell survival, and the combination of electrical stimulation and neurotrophic factors could prove a most effective intervention.
Altschuler
R A
RA
Kresge Hearing Research Institute, University of Michigan, Ann Arbor 48109-0506, USA. shuler@umich.edu
Cho
Y
Y
Ylikoski
J
J
Pirvola
U
U
Magal
E
E
Miller
J M
JM
D000617:Aminoglycosides; D000818:Animals; D000900:Anti-Bacterial Agents / Q000009:adverse effects; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology* / Q000627:therapeutic use; D003638:Deafness / Q000139:chemically induced / Q000188:drug therapy; D005346:Fibroblast Growth Factors / Q000494:pharmacology / Q000627:therapeutic use; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors / Q000494:pharmacology* / Q000627:therapeutic use; D009419:Nerve Tissue Proteins / Q000494:pharmacology* / Q000627:therapeutic use; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology; D013136:Spiral Ganglion / Q000187:drug effects* / Q000502:physiology
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D019208:Brain-Derived Neurotrophic Factor; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D005346:Fibroblast Growth Factors