Document Detail

Effects of brain-derived neurotrophic factor (BDNF) and electrical stimulation on survival and function of cochlear spiral ganglion neurons in deafened, developing cats.
MedLine Citation:
PMID:  23392612     Owner:  NLM     Status:  MEDLINE    
Both neurotrophic support and neural activity are required for normal postnatal development and survival of cochlear spiral ganglion (SG) neurons. Previous studies in neonatally deafened cats demonstrated that electrical stimulation (ES) from a cochlear implant can promote improved SG survival but does not completely prevent progressive neural degeneration. Neurotrophic agents combined with an implant may further improve neural survival. Short-term studies in rodents have shown that brain-derived neurotrophic factor (BDNF) promotes SG survival after deafness and may be additive to trophic effects of stimulation. Our recent study in neonatally deafened cats provided the first evidence of BDNF neurotrophic effects in the developing auditory system over a prolonged duration Leake et al. (J Comp Neurol 519:1526-1545, 2011). Ten weeks of intracochlear BDNF infusion starting at 4 weeks of age elicited significant improvement in SG survival and larger soma size compared to contralateral. In the present study, the same deafening and BDNF infusion procedures were combined with several months of ES from an implant. After combined BDNF + ES, a highly significant increase in SG numerical density (>50 % improvement re: contralateral) was observed, which was significantly greater than the neurotrophic effect seen with ES-only over comparable durations. Combined BDNF + ES also resulted in a higher density of myelinated radial nerve fibers within the osseous spiral lamina. However, substantial ectopic and disorganized sprouting of these fibers into the scala tympani also occurred, which may be deleterious to implant function. EABR thresholds improved (re: initial thresholds at time of implantation) on the chronically stimulated channels of the implant. Terminal electrophysiological studies recording in the inferior colliculus (IC) revealed that the basic cochleotopic organization was intact in the midbrain in all studied groups. In deafened controls or after ES-only, lower IC thresholds were correlated with more selective activation widths as expected, but no such correlation was seen after BDNF + ES due to much greater variability in both measures.
Patricia A Leake; Olga Stakhovskaya; Alexander Hetherington; Stephen J Rebscher; Ben Bonham
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2013-02-08
Journal Detail:
Title:  Journal of the Association for Research in Otolaryngology : JARO     Volume:  14     ISSN:  1438-7573     ISO Abbreviation:  J. Assoc. Res. Otolaryngol.     Publication Date:  2013 Apr 
Date Detail:
Created Date:  2013-03-12     Completed Date:  2013-09-06     Revised Date:  2014-04-01    
Medline Journal Info:
Nlm Unique ID:  100892857     Medline TA:  J Assoc Res Otolaryngol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  187-211     Citation Subset:  IM    
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MeSH Terms
Auditory Threshold / drug effects,  physiology
Brain-Derived Neurotrophic Factor / pharmacology*
Cell Survival / drug effects,  physiology
Cochlea / growth & development,  innervation*,  physiopathology
Cochlear Implants
Deafness / physiopathology*,  therapy*
Disease Models, Animal
Electric Stimulation Therapy*
Electrophysiological Phenomena / drug effects,  physiology
Neovascularization, Physiologic / drug effects,  physiology
Neurons / cytology,  drug effects,  physiology*
Spiral Ganglion / cytology,  drug effects,  physiology*
Grant Support
HHS-N-263-2007-00054-C//PHS HHS; HHSN263200700054C/DC/NIDCD NIH HHS
Reg. No./Substance:
0/Brain-Derived Neurotrophic Factor

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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