PMID- 23392612
OWN - NLM
STAT- MEDLINE
DCOM- 20130906
LR  - 20211021
IS  - 1438-7573 (Electronic)
IS  - 1525-3961 (Print)
IS  - 1438-7573 (Linking)
VI  - 14
IP  - 2
DP  - 2013 Apr
TI  - Effects of brain-derived neurotrophic factor (BDNF) and electrical stimulation on 
      survival and function of cochlear spiral ganglion neurons in deafened, developing 
      cats.
PG  - 187-211
LID - 10.1007/s10162-013-0372-5 [doi]
AB  - 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.
FAU - Leake, Patricia A
AU  - Leake PA
AD  - Epstein Hearing Research Laboratory, Department of Otolaryngology-Head and Neck 
      Surgery, University of California San Francisco, 533 Parnassus Ave., San 
      Francisco, CA 94143-0526, USA. pleake@ohns.ucsf.edu
FAU - Stakhovskaya, Olga
AU  - Stakhovskaya O
FAU - Hetherington, Alexander
AU  - Hetherington A
FAU - Rebscher, Stephen J
AU  - Rebscher SJ
FAU - Bonham, Ben
AU  - Bonham B
LA  - eng
GR  - HHS-N-263-2007-00054-C/PHS HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20130208
PL  - United States
TA  - J Assoc Res Otolaryngol
JT  - Journal of the Association for Research in Otolaryngology : JARO
JID - 100892857
RN  - 0 (Brain-Derived Neurotrophic Factor)
SB  - IM
MH  - Animals
MH  - Auditory Threshold/drug effects/physiology
MH  - Brain-Derived Neurotrophic Factor/*pharmacology
MH  - Cats
MH  - Cell Survival/drug effects/physiology
MH  - Cochlea/growth & development/*innervation/physiopathology
MH  - Cochlear Implants
MH  - Deafness/*physiopathology/*therapy
MH  - Disease Models, Animal
MH  - *Electric Stimulation Therapy
MH  - Electrophysiological Phenomena/drug effects/physiology
MH  - Neovascularization, Physiologic/drug effects/physiology
MH  - Neurons/cytology/drug effects/*physiology
MH  - Spiral Ganglion/cytology/drug effects/*physiology
PMC - PMC3660916
EDAT- 2013/02/09 06:00
MHDA- 2013/09/07 06:00
PMCR- 2014/04/01
CRDT- 2013/02/09 06:00
PHST- 2012/05/10 00:00 [received]
PHST- 2013/01/03 00:00 [accepted]
PHST- 2013/02/09 06:00 [entrez]
PHST- 2013/02/09 06:00 [pubmed]
PHST- 2013/09/07 06:00 [medline]
PHST- 2014/04/01 00:00 [pmc-release]
AID - 372 [pii]
AID - 10.1007/s10162-013-0372-5 [doi]
PST - ppublish
SO  - J Assoc Res Otolaryngol. 2013 Apr;14(2):187-211. doi: 10.1007/s10162-013-0372-5. 
      Epub 2013 Feb 8.