PMID- 17416474
OWN - NLM
STAT- MEDLINE
DCOM- 20070703
LR  - 20220129
IS  - 0378-5955 (Print)
IS  - 1878-5891 (Electronic)
IS  - 0378-5955 (Linking)
VI  - 228
IP  - 1-2
DP  - 2007 Jun
TI  - Cochlear implants and ex vivo BDNF gene therapy protect spiral ganglion neurons.
PG  - 180-7
AB  - Spiral ganglion neurons often degenerate in the deaf ear, compromising the 
      function of cochlear implants. Cochlear implant function can be improved by good 
      preservation of the spiral ganglion neurons, which are the target of electrical 
      stimulation by the implant. Brain derived neurotrophic factor (BDNF) has 
      previously been shown to enhance spiral ganglion survival in experimentally 
      deafened ears. Providing enhanced levels of BDNF in human ears may be 
      accomplished by one of several different methods. The goal of these experiments 
      was to test a modified design of the cochlear implant electrode that includes a 
      coating of fibroblast cells transduced by a viral vector with a BDNF gene insert. 
      To accomplish this type of ex vivo gene transfer, we transduced guinea pig 
      fibroblasts with an adenovirus with a BDNF gene cassette insert, and determined 
      that these cells secreted BDNF. We then attached BDNF-secreting cells to the 
      cochlear implant electrode via an agarose gel, and implanted the electrode in the 
      scala tympani. We determined that the BDNF expressing electrodes were able to 
      preserve significantly more spiral ganglion neurons in the basal turns of the 
      cochlea after 48 days of implantation when compared to control electrodes. This 
      protective effect decreased in the higher cochlear turns. The data demonstrate 
      the feasibility of combining cochlear implant therapy with ex vivo gene transfer 
      for enhancing spiral ganglion neuron survival.
FAU - Rejali, Darius
AU  - Rejali D
AD  - Kresge Hearing Research Institute, University of Michigan Medical School, Ann 
      Arbor, Michigan, USA, and University Hospitals Warwickshire and Coventry NHS 
      Trust, Coventry CV2 2DX, UK.
FAU - Lee, Valerie A
AU  - Lee VA
FAU - Abrashkin, Karen A
AU  - Abrashkin KA
FAU - Humayun, Nousheen
AU  - Humayun N
FAU - Swiderski, Donald L
AU  - Swiderski DL
FAU - Raphael, Yehoash
AU  - Raphael Y
LA  - eng
GR  - 8-P41-EB-2030/EB/NIBIB NIH HHS/United States
GR  - P30-DC05188/DC/NIDCD NIH HHS/United States
GR  - P30 DC005188/DC/NIDCD NIH HHS/United States
GR  - R01 DC001634-14/DC/NIDCD NIH HHS/United States
GR  - G12/ACT_/RNID/United Kingdom
GR  - DC007634/DC/NIDCD NIH HHS/United States
GR  - R01 DC005401-03/DC/NIDCD NIH HHS/United States
GR  - P41 EB002030/EB/NIBIB NIH HHS/United States
GR  - R01 DC001634/DC/NIDCD NIH HHS/United States
GR  - R01 DC005401/DC/NIDCD NIH HHS/United States
GR  - R01 DC007634/DC/NIDCD NIH HHS/United States
GR  - R55 DC007634/DC/NIDCD NIH HHS/United States
GR  - P30 DC005188-07/DC/NIDCD NIH HHS/United States
GR  - DC05401/DC/NIDCD NIH HHS/United States
GR  - R01 DC007634-04/DC/NIDCD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20070307
PL  - Netherlands
TA  - Hear Res
JT  - Hearing research
JID - 7900445
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 59-01-8 (Kanamycin)
RN  - 9012-36-6 (Sepharose)
RN  - M5DP350VZV (Ethacrynic Acid)
SB  - IM
MH  - Adenoviridae/genetics
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/*biosynthesis/genetics
MH  - Cell Survival
MH  - Cells, Cultured
MH  - *Cochlear Implantation
MH  - *Cochlear Implants
MH  - Deafness/chemically induced/genetics/metabolism/pathology/surgery/*therapy
MH  - Disease Models, Animal
MH  - Ethacrynic Acid
MH  - Feasibility Studies
MH  - Fibroblasts/metabolism
MH  - Genetic Therapy/*instrumentation/methods
MH  - Genetic Vectors
MH  - Guinea Pigs
MH  - Kanamycin
MH  - Nerve Degeneration/chemically induced/genetics/metabolism/pathology/*prevention & 
      control
MH  - Neurons/metabolism
MH  - Prosthesis Design
MH  - Sepharose/metabolism
MH  - Spiral Ganglion/*metabolism/pathology
MH  - *Transduction, Genetic
PMC - PMC2692458
MID - NIHMS23844
EDAT- 2007/04/10 09:00
MHDA- 2007/07/04 09:00
PMCR- 2009/06/08
CRDT- 2007/04/10 09:00
PHST- 2006/05/30 00:00 [received]
PHST- 2007/02/21 00:00 [revised]
PHST- 2007/02/21 00:00 [accepted]
PHST- 2007/04/10 09:00 [pubmed]
PHST- 2007/07/04 09:00 [medline]
PHST- 2007/04/10 09:00 [entrez]
PHST- 2009/06/08 00:00 [pmc-release]
AID - S0378-5955(07)00063-9 [pii]
AID - 10.1016/j.heares.2007.02.010 [doi]
PST - ppublish
SO  - Hear Res. 2007 Jun;228(1-2):180-7. doi: 10.1016/j.heares.2007.02.010. Epub 2007 
      Mar 7.