PMID- 15372491
OWN - NLM
STAT- MEDLINE
DCOM- 20050207
LR  - 20181130
IS  - 0360-4012 (Print)
IS  - 0360-4012 (Linking)
VI  - 78
IP  - 1
DP  - 2004 Oct 1
TI  - Delayed neurotrophic treatment preserves nerve survival and electrophysiological 
      responsiveness in neomycin-deafened guinea pigs.
PG  - 75-86
AB  - Benefits of cochlear prostheses for the deaf are dependent on survival and 
      excitability of the auditory nerve. Degeneration of deafferented auditory nerve 
      fibers is prevented and excitability maintained by immediate replacement therapy 
      with exogenous neurotrophic factors, in vivo. It is important to know whether 
      such interventions are effective after a delay following deafness, typical for 
      the human situation. This study evaluated the efficacy of brain-derived 
      neurotrophic factor (BDNF) and ciliary neurotrophic factor axokine-1 analogue 
      (CNTF Ax1) application, 2 or 6 weeks postdeafening, in preventing further 
      degeneration and a decrease in excitability. Guinea pigs were deafened and 
      implanted with intracochlear stimulating electrodes, a scala tympani 
      cannula-osmotic pump system, and auditory brainstem response (ABR) recording 
      electrodes. Subjects received BDNF + CNTF Ax1 or artificial perilymph (AP) 
      treatment for 27 days, beginning at 2 or 6 weeks following deafening. Electrical 
      (E) ABR thresholds increased following deafening. After 1 week, in the 
      2-weeks-delayed neurotrophic factor treatment group, EABR thresholds decreased 
      relative to AP controls, which were statistically significant at 2 weeks. In the 
      6-week delay group, a tendency to enhanced EABR sensitivity began at 2 weeks of 
      treatment and increased thereafter, with a significant difference between 
      neurotrophic factor- and AP-treated groups across the treatment period. A clear, 
      statistically significant, enhanced survival of spiral ganglion cells was seen in 
      both neurotrophic factor treatment groups relative to AP controls. These findings 
      demonstrate that BDNF + CNTF Ax1 can act to delay or possibly even reverse 
      degenerative and, likely apoptotic, processes well after they have been 
      activated. These survival factors can rescue cells from death and enhance 
      electrical excitability, even during the period of degeneration and cell loss 
      when the spiral ganglion cell population is reduced by >50% (6 weeks). It is 
      noteworthy that this same degree of ganglion cell loss, secondary to receptor 
      damage, is typically observed after a period equivalent to some years of deafness 
      in humans.
CI  - 2004 Wiley-Liss, Inc.
FAU - Yamagata, Takahiko
AU  - Yamagata T
AD  - Center for Hearing and Communication Research and Department of Clinical 
      Neuroscience, Karolinska Institutet, Stockholm, Sweden.
FAU - Miller, Josef M
AU  - Miller JM
FAU - Ulfendahl, Mats
AU  - Ulfendahl M
FAU - Olivius, N Petri
AU  - Olivius NP
FAU - Altschuler, Richard A
AU  - Altschuler RA
FAU - Pyykko, Ilmari
AU  - Pyykko I
FAU - Bredberg, Goran
AU  - Bredberg G
LA  - eng
GR  - R01 DC003820/DC/NIDCD NIH HHS/United States
GR  - DC03820/DC/NIDCD NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Neurosci Res
JT  - Journal of neuroscience research
JID - 7600111
RN  - 0 (Ciliary Neurotrophic Factor)
RN  - 0 (Nerve Growth Factors)
RN  - I16QD7X297 (Neomycin)
SB  - IM
MH  - Animals
MH  - Catheterization
MH  - Cell Survival/drug effects/physiology
MH  - Ciliary Neurotrophic Factor/administration & dosage
MH  - Cochlear Nerve/*drug effects/*physiology
MH  - Deafness/chemically induced/*drug therapy/*physiopathology
MH  - Electrophysiology
MH  - Female
MH  - Guinea Pigs
MH  - Infusion Pumps, Implantable
MH  - Neomycin/*toxicity
MH  - Nerve Growth Factors/*administration & dosage
MH  - Time Factors
EDAT- 2004/09/17 05:00
MHDA- 2005/02/08 09:00
CRDT- 2004/09/17 05:00
PHST- 2004/09/17 05:00 [pubmed]
PHST- 2005/02/08 09:00 [medline]
PHST- 2004/09/17 05:00 [entrez]
AID - 10.1002/jnr.20239 [doi]
PST - ppublish
SO  - J Neurosci Res. 2004 Oct 1;78(1):75-86. doi: 10.1002/jnr.20239.