PMID- 27773647
OWN - NLM
STAT- MEDLINE
DCOM- 20180108
LR  - 20181203
IS  - 1878-5891 (Electronic)
IS  - 0378-5955 (Print)
IS  - 0378-5955 (Linking)
VI  - 342
DP  - 2016 Dec
TI  - Effects of brain-derived neurotrophic factor (BDNF) on the cochlear nucleus in 
      cats deafened as neonates.
PG  - 134-143
LID - S0378-5955(16)30177-0 [pii]
LID - 10.1016/j.heares.2016.10.011 [doi]
AB  - Many previous studies have shown significant neurotrophic effects of 
      intracochlear delivery of BDNF in preventing degeneration of cochlear spiral 
      ganglion (SG) neurons after deafness in rodents and our laboratory has shown 
      similar results in developing cats deafened prior to hearing onset. This study 
      examined the morphology of the cochlear nucleus (CN) in a group of neonatally 
      deafened cats from a previous study in which infusion of BDNF elicited a 
      significant improvement in survival of the SG neurons. Five cats were deafened by 
      systemic injections of neomycin sulfate (60 mg/kg, SQ, SID) starting one day 
      after birth, and continuing for 16-18 days until auditory brainstem response 
      (ABR) testing demonstrated profound bilateral hearing loss. The animals were 
      implanted unilaterally at about 1 month of age using custom-designed electrodes 
      with a drug-delivery cannula connected to an osmotic pump. BDNF (94 mug/ml; 
      0.25 mul/hr) was delivered for 10 weeks. The animals were euthanized and studied 
      at 14-23 weeks of age. Consistent with the neurotrophic effects of BDNF on SG 
      survival, the total CN volume in these animals was significantly larger on the 
      BDNF-treated side than on the contralateral side. However, total CN volume, both 
      ipsi- and contralateral to the implants in these deafened juvenile animals, was 
      markedly smaller than the CN in normal adult animals, reflecting the severe 
      effects of deafness on the central auditory system during development. Data from 
      the individual major CN subdivisions (DCN, Dorsal Cochlear Nucleus; PVCN, 
      Posteroventral Cochlear Nucleus; AVCN, Anteroventral Cochlear Nucleus) also were 
      analyzed. A significant difference was observed between the BDNF-treated and 
      control sides only in the AVCN. Measurements of the cross-sectional areas of 
      spherical cells showed that cells were significantly larger in the AVCN 
      ipsilateral to the implant than on the contralateral side. Further, the numerical 
      density of spherical cells was significantly lower in the AVCN ipsilateral to the 
      implant than on the contralateral side, consistent with the larger AVCN volume 
      observed with BDNF treatment. Together, findings indicate significant 
      neurotrophic effects of intracochlear BDNF infusion on the developing CN.
CI  - Copyright (c) 2016 Elsevier B.V. All rights reserved.
FAU - Kandathil, Cherian K
AU  - Kandathil CK
AD  - Epstein Laboratory, Dept. of Otolaryngology-Head & Neck Surgery, University of 
      California San Francisco, 533 Parnassus Avenue, Room U490, San Francisco, CA 
      94143-0526, USA. Electronic address: cherian.kandathil@outlook.com.
FAU - Stakhovskaya, Olga
AU  - Stakhovskaya O
AD  - Epstein Laboratory, Dept. of Otolaryngology-Head & Neck Surgery, University of 
      California San Francisco, 533 Parnassus Avenue, Room U490, San Francisco, CA 
      94143-0526, USA. Electronic address: ostackovsky@hotmail.com.
FAU - Leake, Patricia A
AU  - Leake PA
AD  - Epstein Laboratory, Dept. of Otolaryngology-Head & Neck Surgery, University of 
      California San Francisco, 533 Parnassus Avenue, Room U490, San Francisco, CA 
      94143-0526, USA. Electronic address: Pat.Leake@ucsf.edu.
LA  - eng
GR  - HHSN263200700054C/OL/OLAO NIH HHS/United States
GR  - R01 DC013067/DC/NIDCD NIH HHS/United States
PT  - Journal Article
DEP - 20161020
PL  - Netherlands
TA  - Hear Res
JT  - Hearing research
JID - 7900445
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - I16QD7X297 (Neomycin)
SB  - IM
MH  - Animals
MH  - Animals, Newborn
MH  - Brain-Derived Neurotrophic Factor/*administration & dosage
MH  - Cats
MH  - Cochlear Nucleus/*drug effects/growth & development/*pathology
MH  - Deafness/chemically induced/*drug therapy/*pathology
MH  - Drug Delivery Systems
MH  - Evoked Potentials, Auditory, Brain Stem
MH  - Neomycin/toxicity
MH  - Organ Size/drug effects
MH  - Spiral Ganglion/drug effects/pathology
PMC - PMC5140101
MID - NIHMS824543
OTO - NOTNLM
OT  - Aminoglycoside ototoxicity
OT  - BDNF
OT  - Cochlear nucleus
OT  - Neonatal deafness
OT  - Neurotrophic effects
EDAT- 2016/10/25 06:00
MHDA- 2018/01/09 06:00
PMCR- 2017/12/01
CRDT- 2016/11/06 06:00
PHST- 2016/05/06 00:00 [received]
PHST- 2016/08/23 00:00 [revised]
PHST- 2016/10/15 00:00 [accepted]
PHST- 2016/10/25 06:00 [pubmed]
PHST- 2018/01/09 06:00 [medline]
PHST- 2016/11/06 06:00 [entrez]
PHST- 2017/12/01 00:00 [pmc-release]
AID - S0378-5955(16)30177-0 [pii]
AID - 10.1016/j.heares.2016.10.011 [doi]
PST - ppublish
SO  - Hear Res. 2016 Dec;342:134-143. doi: 10.1016/j.heares.2016.10.011. Epub 2016 Oct 
      20.