PMID- 18243608
OWN - NLM
STAT- MEDLINE
DCOM- 20081028
LR  - 20230613
IS  - 0378-5955 (Print)
IS  - 0378-5955 (Linking)
VI  - 242
IP  - 1-2
DP  - 2008 Aug
TI  - Neurotrophins and electrical stimulation for protection and repair of spiral 
      ganglion neurons following sensorineural hearing loss.
PG  - 100-9
LID - 10.1016/j.heares.2007.12.005 [doi]
AB  - Exogenous neurotrophins (NTs) have been shown to rescue spiral ganglion neurons 
      (SGNs) from degeneration following a sensorineural hearing loss (SNHL). 
      Furthermore, chronic electrical stimulation (ES) has been shown to retard SGN 
      degeneration in some studies but not others. Since there is evidence of even 
      greater SGN rescue when NT administration is combined with ES, we examined 
      whether chronic ES can maintain SGN survival long after cessation of NT delivery. 
      Young adult guinea pigs were profoundly deafened using ototoxic drugs; five days 
      later they were unilaterally implanted with an electrode array and drug delivery 
      system. Brain derived neurotrophic factor (BDNF) was continuously delivered to 
      the scala tympani over a four week period while the animal simultaneously 
      received ES via bipolar electrodes in the basal turn (i.e., turn 1) scala 
      tympani. One cohort (n=5) received ES for six weeks (i.e., including a two week 
      period after the cessation of BDNF delivery; ES(6)); a second cohort (n=5) 
      received ES for 10 weeks (i.e., a six week period following cessation of BDNF 
      delivery; ES(10)). The cochleae were harvested for histology and SGN density 
      determined for each cochlear turn for comparison with normal hearing controls 
      (n=4). The withdrawal of BDNF resulted in a rapid loss of SGNs in turns 2-4 of 
      the deafened/BDNF-treated cochleae; this was significant as early as two weeks 
      following removal of the NT when compared with normal controls (p<0.05). 
      Importantly, there was not a significant reduction in SGNs in turn 1 (i.e., 
      adjacent to the electrode array) two and six weeks after NT removal, as compared 
      with normal controls. This result suggests that chronic ES can prevent the rapid 
      loss of SGNs that occurs after the withdrawal of exogenous NTs. Implications for 
      the clinical delivery of NTs are discussed.
FAU - Shepherd, Robert K
AU  - Shepherd RK
AD  - The Bionic Ear Institute, 384-388 Albert Street, East Melbourne, Victoria 3002, 
      Australia. rshepherd@bionicear.org
FAU - Coco, Anne
AU  - Coco A
FAU - Epp, Stephanie B
AU  - Epp SB
LA  - eng
GR  - HHSN263200700053C/NH/NIH HHS/United States
GR  - N01 DC031005/DC/NIDCD NIH HHS/United States
PT  - Journal Article
DEP - 20071228
PL  - Netherlands
TA  - Hear Res
JT  - Hearing research
JID - 7900445
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Nerve Growth Factors)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/pharmacology
MH  - Cochlea/innervation/pathology
MH  - Electric Stimulation
MH  - Guinea Pigs
MH  - Hearing Loss, Sensorineural/*physiopathology
MH  - Microelectrodes
MH  - Models, Animal
MH  - Nerve Degeneration/physiopathology/prevention & control
MH  - Nerve Growth Factors/*pharmacology
MH  - Spiral Ganglion/*drug effects/*physiopathology
PMC - PMC2630855
MID - NIHMS66643
EDAT- 2008/02/05 09:00
MHDA- 2008/10/29 09:00
PMCR- 2009/08/01
CRDT- 2008/02/05 09:00
PHST- 2007/07/12 00:00 [received]
PHST- 2007/12/05 00:00 [revised]
PHST- 2007/12/12 00:00 [accepted]
PHST- 2008/02/05 09:00 [pubmed]
PHST- 2008/10/29 09:00 [medline]
PHST- 2008/02/05 09:00 [entrez]
PHST- 2009/08/01 00:00 [pmc-release]
AID - S0378-5955(07)00295-X [pii]
AID - 10.1016/j.heares.2007.12.005 [doi]
PST - ppublish
SO  - Hear Res. 2008 Aug;242(1-2):100-9. doi: 10.1016/j.heares.2007.12.005. Epub 2007 
      Dec 28.