Skip to main content

Advertisement

SpringerLink
Log in

Effects of Brain-Derived Neurotrophic Factor (BDNF) and Electrical Stimulation on Survival and Function of Cochlear Spiral Ganglion Neurons in Deafened, Developing Cats

  • Research Article
  • Published:
Journal of the Association for Research in Otolaryngology Aims and scope Submit manuscript

Abstract

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

FIG. 1
FIG. 2
FIG. 3
FIG. 4
FIG. 5
FIG. 6
FIG. 7
FIG. 8
FIG. 9
FIG. 10
FIG. 11
FIG. 12

Similar content being viewed by others

References

  • Agterberg MJH, Versnel H, de Groot JCMJ et al (2008) Morphological changes in spiral ganglion cells after intracochlear application of brain-derived neurotrophic factor in deafened guinea pigs. Hear Res 244:25–34. doi:10.1016/j.heares.2008.07.004

    Article  PubMed  CAS  Google Scholar 

  • Agterberg MJH, Versnel H, van Dijk LM et al (2009) Enhanced survival of spiral ganglion cells after cessation of treatment with brain-derived neurotrophic factor in deafened guinea pigs. J Assoc Res Otolaryngol 10:355–367. doi:10.1007/s10162-009-0170-2

    Article  PubMed  Google Scholar 

  • Araki S, Kawano A, Seldon L et al (1998) Effects of chronic electrical stimulation on spiral ganglion neuron survival and size in deafened kittens. Laryngoscope 108:687–695. doi:10.1097/00005537-199805000-00012

    Article  PubMed  CAS  Google Scholar 

  • Chikar JA, Colesa DJ, Swiderski DL et al (2008) Over-expression of BDNF by adenovirus with concurrent electrical stimulation improves cochlear implant thresholds and survival of auditory neurons. Hear Res 245:24–34. doi:10.1016/j.heares.2008.08.005

    Article  PubMed  CAS  Google Scholar 

  • Coco A, Epp SB, Fallon JB et al (2007) Does cochlear implantation and electrical stimulation affect residual hair cells and spiral ganglion neurons? Hear Res 225:60–70. doi:10.1016/j.heares.2006.12.004

    Article  PubMed  Google Scholar 

  • Djalali S, Holtje M, Grosse G et al (2005) Effects of brain-derived neurotrophic factor (BDNF) on glial cells and serotonergic neurons during development. J Neurochem 92:616–627

    Google Scholar 

  • Don M, Elberling C (1994) Evaluating residual background noise in human auditory brain-stem responses. J Acoust Soc Am 96:2746–2757

    Article  PubMed  CAS  Google Scholar 

  • Drennan WR, Rubinstein JT (2008) Music perception in cochlear implant users and its relationship with psychophysical capabilities. J Rehabil Res Dev 45:779–789

    Article  PubMed  Google Scholar 

  • Elverland HH, Mair IW (1980) Hereditary deafness in the cat. An electron microscopic study of the spiral ganglion. Acta Otolaryngol 90:360–369

    Article  PubMed  CAS  Google Scholar 

  • Endo T, Nakagawa T, Kita T et al (2005) Novel strategy for treatment of inner ears using a biodegradable gel. Laryngoscope 115:2016–2020. doi:10.1097/01.mlg.0000183020.32435.59

    Article  PubMed  CAS  Google Scholar 

  • Fariñas I, Jones KR, Tessarollo L et al (2001) Spatial shaping of cochlear innervation by temporally regulated neurotrophin expression. J Neurosci 21:6170–6180

    PubMed  Google Scholar 

  • Firszt JB, Holden LK, Skinner MW et al (2004) Recognition of speech presented at soft to loud levels by adult cochlear implant recipients of three cochlear implant systems. Ear Hear 25:375–387

    Article  PubMed  Google Scholar 

  • Fritzsch B, Pirvola U, Ylikoski J (1999) Making and breaking the innervation of the ear: neurotrophic support during ear development and its clinical implications. Cell Tissue Res 295:369–382

    Article  PubMed  CAS  Google Scholar 

  • Gao WQ, Zheng JL, Karihaloo M (1995) Neurotrophin-4/5 (NT-4/5) and brain-derived neurotrophic factor (BDNF) act at later stages of cerebellar granule cell differentiation. J Neurosci 15:2656–2667

    PubMed  CAS  Google Scholar 

  • Geers AE (2004) Speech, language, and reading skills after early cochlear implantation. Arch Otolaryngol Head Neck Surg 130:634–638. doi:10.1001/archotol.130.5.634

    Article  PubMed  Google Scholar 

  • Gillespie LN, Clark GM, Bartlett PF, Marzella PL (2003) BDNF-induced survival of auditory neurons in vivo: Cessation of treatment leads to accelerated loss of survival effects. J Neurosci Res 71:785–790. doi:10.1002/jnr.10542

    Article  PubMed  CAS  Google Scholar 

  • Glueckert R, Bitsche M, Miller JM et al (2008) Deafferentation-associated changes in afferent and efferent processes in the guinea pig cochlea and afferent regeneration with chronic intrascalar brain-derived neurotrophic factor and acidic fibroblast growth factor. J Comp Neurol 507:1602–1621. doi:10.1002/cne.21619

    Article  PubMed  Google Scholar 

  • Hansen MR, Zha XM, Bok J, Green SH (2001) Multiple distinct signal pathways, including an autocrine neurotrophic mechanism, contribute to the survival-promoting effect of depolarization on spiral ganglion neurons in vitro. J Neurosci 21:2256–2267

    PubMed  CAS  Google Scholar 

  • Hansen MR, Bok J, Devaiah AK et al (2003) Ca2+/calmodulin-dependent protein kinases II and IV both promote survival but differ in their effects on axon growth in spiral ganglion neurons. J Neurosci Res 72:169–184. doi:10.1002/jnr.10551

    Article  PubMed  CAS  Google Scholar 

  • Hartmann R, Topp G, Klinke R (1984) Discharge patterns of cat primary auditory fibers with electrical stimulation of the cochlea. Hear Res 13:47–62

    Article  PubMed  CAS  Google Scholar 

  • Hartshorn DO, Miller JM, Altschuler RA (1991) Protective effect of electrical stimulation in the deafened guinea pig cochlea. Otolaryngol Head Neck Surg 104:311–319

    PubMed  CAS  Google Scholar 

  • Hegarty JL, Kay AR, Green SH (1997) Trophic support of cultured spiral ganglion neurons by depolarization exceeds and is additive with that by neurotrophins or cAMP and requires elevation of [Ca2+]i within a set range. J Neurosci 17:1959–1970

    PubMed  CAS  Google Scholar 

  • Hendricks JL, Chikar JA, Crumling MA et al (2008) Localized cell and drug delivery for auditory prostheses. Hear Res 242:117–131. doi:10.1016/j.heares.2008.06.003

    Article  PubMed  CAS  Google Scholar 

  • Hochmair I, Nopp P, Jolly C et al (2006) MED-EL Cochlear implants: state of the art and a glimpse into the future. Trends Amplif 10:201–219. doi:10.1177/1084713806296720

    Article  PubMed  Google Scholar 

  • Holden, LK, Finley, CC, Firszt JB, et al (2013) Factors affecting open-set word recognition in adults with cochlear implants. Ear Hear. doi:10.1097/AUD.0b013e3182741aa7

  • Kanzaki S, Stöver T, Kawamoto K et al (2002) Glial cell line-derived neurotrophic factor and chronic electrical stimulation prevent VIII cranial nerve degeneration following denervation. J Comp Neurol 454:350–360. doi:10.1002/cne.10480

    Article  PubMed  CAS  Google Scholar 

  • Kermani P, Hempstead B (2007) Brain-derived neurotrophic factor: a newly described mediator of angiogenesis. Trends Cardiovasc Med 17:140–143. doi:10.1016/j.tcm.2007.03.002

    Article  PubMed  CAS  Google Scholar 

  • Kiang NY, Rho JM, Northrop CC et al (1982) Hair-cell innervation by spiral ganglion cells in adult cats. Science 217:175–177

    Article  PubMed  CAS  Google Scholar 

  • Korsching S (1993) The neurotrophic factor concept: a reexamination. J Neurosci 13:2739–2748

    PubMed  CAS  Google Scholar 

  • Leake PA, Hradek GT (1988) Cochlear pathology of long term neomycin induced deafness in cats. Hear Res 33:11–33

    Article  PubMed  CAS  Google Scholar 

  • Leake PA, Kuntz AL, Moore CM, Chambers PL (1997) Cochlear pathology induced by aminoglycoside ototoxicity during postnatal maturation in cats. Hear Res 113:117–132

    Article  PubMed  CAS  Google Scholar 

  • Leake PA, Hradek GT, Snyder RL (1999) Chronic electrical stimulation by a cochlear implant promotes survival of spiral ganglion neurons after neonatal deafness. J Comp Neurol 412:543–562

    Article  PubMed  CAS  Google Scholar 

  • Leake PA, Hradek GT, Vollmer M, Rebscher SJ (2007) Neurotrophic effects of GM1 ganglioside and electrical stimulation on cochlear spiral ganglion neurons in cats deafened as neonates. J Comp Neurol 501:837–853. doi:10.1002/cne.21275

    Article  PubMed  CAS  Google Scholar 

  • Leake PA, Hradek GT, Bonham BH, Snyder RL (2008a) Topography of auditory nerve projections to the cochlear nucleus in cats after neonatal deafness and electrical stimulation by a cochlear implant. J Assoc Res Otolaryngol 9:349–372. doi:10.1007/s10162-008-0127-x

    Article  PubMed  Google Scholar 

  • Leake PA, Stakhovskaya O, Hradek GT, Hetherington AM (2008b) Factors influencing neurotrophic effects of electrical stimulation in the deafened developing auditory system. Hear Res 242:86–99. doi:10.1016/j.heares.2008.06.002

    Article  PubMed  Google Scholar 

  • Leake PA, Hradek GT, Hetherington AM, Stakhovskaya O (2011) Brain-derived neurotrophic factor promotes cochlear spiral ganglion cell survival and function in deafened, developing cats. J Comp Neurol 519:1526–1545. doi:10.1002/cne.22582

    Article  PubMed  CAS  Google Scholar 

  • Li L, Parkins CW, Webster DB (1999) Does electrical stimulation of deaf cochleae prevent spiral ganglion degeneration? Hear Res 133:27–39

    Article  PubMed  CAS  Google Scholar 

  • Liberman MC (1982) The cochlear frequency map for the cat: labeling auditory-nerve fibers of known characteristic frequency. J Acoust Soc Am 72:1441–1449

    Article  PubMed  CAS  Google Scholar 

  • Liberman MC, Kiang NY (1978) Acoustic trauma in cats. Cochlear pathology and auditory-nerve activity. Acta Otolaryngol Suppl 358:1–63

    PubMed  CAS  Google Scholar 

  • Liberman MC, Dodds LW, Pierce S (1990) Afferent and efferent innervation of the cat cochlea: quantitative analysis with light and electron microscopy. J Comp Neurol 301:443–460. doi:10.1002/cne.903010309

    Article  PubMed  CAS  Google Scholar 

  • Lousteau RJ (1987) Increased spiral ganglion cell survival in electrically stimulated, deafened guinea pig cochleae. Laryngoscope 97:836–842

    Article  PubMed  CAS  Google Scholar 

  • Maruyama J, Miller JM, Ulfendahl M (2008) Glial cell line-derived neurotrophic factor and antioxidants preserve the electrical responsiveness of the spiral ganglion neurons after experimentally induced deafness. Neurobiol Dis 29:14–21. doi:10.1016/j.nbd.2007.07.026

    Article  PubMed  CAS  Google Scholar 

  • McGuinness SL, Shepherd RK (2005) Exogenous BDNF rescues rat spiral ganglion neurons in vivo. Otol Neurotol 26:1064–1072

    Article  PubMed  Google Scholar 

  • Miller AL (2001) Effects of chronic stimulation on auditory nerve survival in ototoxically deafened animals. Hear Res 151:1–14

    Article  PubMed  CAS  Google Scholar 

  • Miller JM, Altschuler RA (1995) Effectiveness of different electrical stimulation conditions in preservation of spiral ganglion cells following deafness. Ann Otol Rhinol Laryngol Suppl 166:57–60

    PubMed  CAS  Google Scholar 

  • Miller JM, Le Prell CG, Prieskorn DM et al (2007) Delayed neurotrophin treatment following deafness rescues spiral ganglion cells from death and promotes regrowth of auditory nerve peripheral processes: effects of brain-derived neurotrophic factor and fibroblast growth factor. J Neurosci Res 85:1959–1969. doi:10.1002/jnr.21320

    Article  PubMed  CAS  Google Scholar 

  • Mitchell A, Miller JM, Finger PA et al (1997) Effects of chronic high-rate electrical stimulation on the cochlea and eighth nerve in the deafened guinea pig. Hear Res 105:30–43

    Article  PubMed  CAS  Google Scholar 

  • Mouton PR (2002) Principles and practices of unbiased stereology: an introduction for bioscientists. The Johns Hopkins University Press, Baltimore

    Google Scholar 

  • Nakaizumi T, Kawamoto K, Minoda R, Raphael Y (2004) Adenovirus-mediated expression of brain-derived neurotrophic factor protects spiral ganglion neurons from ototoxic damage. Audiol Neurootol 9:135–143. doi:10.1159/000077264

    Article  PubMed  CAS  Google Scholar 

  • Nicholas JG, Geers AE (2007) Will they catch up? The role of age at cochlear implantation in the spoken language development of children with severe to profound hearing loss. J Speech Lang Hear Res 50:1048–1062. doi:10.1044/1092-4388(2007/073

    Article  PubMed  Google Scholar 

  • Paasche G, Gibson P, Averbeck T et al (2003) Technical report: modification of a cochlear implant electrode for drug delivery to the inner ear. Otol Neurotol 24:222–227

    Article  PubMed  CAS  Google Scholar 

  • Pettingill LN, Minter RL, Shepherd RK (2008) Schwann cells genetically modified to express neurotrophins promote spiral ganglion neuron survival in vitro. Neuroscience 152:821–828. doi:10.1016/j.neuroscience.2007.11.057

    Article  PubMed  CAS  Google Scholar 

  • Ramekers D, Versnel H, Grolman W, Klis SFL (2012) Neurotrophins and their role in the cochlea. Hear Res 288:19–33. doi:10.1016/j.heares.2012.03.002

    Google Scholar 

  • Rebscher SJ, Hetherington AM, Snyder RL et al (2007) Design and fabrication of multichannel cochlear implants for animal research. J Neurosci Methods 166:1–12. doi:10.1016/j.jneumeth.2007.05.013

    Article  PubMed  Google Scholar 

  • Rejali D, Lee VA, Abrashkin KA et al (2007) Cochlear implants and ex vivo BDNF gene therapy protect spiral ganglion neurons. Hear Res 228:180–187. doi:10.1016/j.heares.2007.02.010

    Article  PubMed  CAS  Google Scholar 

  • Richardson RT, Wise AK, Andrew JK, O’Leary SJ (2008) Novel drug delivery systems for inner ear protection and regeneration after hearing loss. Expert Opin Drug Deliv 5:1059–1076. doi:10.1517/17425247.5.10.1059

    Article  PubMed  CAS  Google Scholar 

  • Roehm PC, Hansen MR (2005) Strategies to preserve or regenerate spiral ganglion neurons. Curr Opin Otolaryngol Head Neck Surg 13:294–300

    Article  PubMed  Google Scholar 

  • Romand MR, Romand R (1990) Development of spiral ganglion cells in mammalian cochlea. J Electron Microsc Tech 15:144–154. doi:10.1002/jemt.1060150206

    Article  PubMed  CAS  Google Scholar 

  • Romand R, Romand MR, Mulle C, Marty R (1980) Early stages of myelination in the spiral ganglion cells of the kitten during development. Acta Otolaryngol 90:391–397

    Article  PubMed  CAS  Google Scholar 

  • Rubel EW, Fritzsch B (2002) Auditory system development: primary auditory neurons and their targets. Annu Rev Neurosci 25:51–101. doi:10.1146/annurev.neuro.25.112701.142849

    Article  PubMed  CAS  Google Scholar 

  • Scheper V, Paasche G, Miller JM et al (2009) Effects of delayed treatment with combined GDNF and continuous electrical stimulation on spiral ganglion cell survival in deafened guinea pigs. J Neurosci Res 87:1389–1399. doi:10.1002/jnr.21964

    Article  PubMed  CAS  Google Scholar 

  • Shepherd RK, Javel E (1997) Electrical stimulation of the auditory nerve. I. Correlation of physiological responses with cochlear status. Hear Res 108:112–144

    Article  PubMed  CAS  Google Scholar 

  • Shepherd RK, Matsushima J, Martin RL, Clark GM (1994) Cochlear pathology following chronic electrical stimulation of the auditory nerve: II. Deafened kittens. Hear Res 81:150–166

    Article  PubMed  CAS  Google Scholar 

  • Shepherd RK, Coco A, Epp SB, Crook JM (2005) Chronic depolarization enhances the trophic effects of brain-derived neurotrophic factor in rescuing auditory neurons following a sensorineural hearing loss. J Comp Neurol 486:145–158. doi:10.1002/cne.20564

    Article  PubMed  CAS  Google Scholar 

  • Shepherd RK, Coco A, Epp SB (2008) Neurotrophins and electrical stimulation for protection and repair of spiral ganglion neurons following sensorineural hearing loss. Hear Res 242:100–109. doi:10.1016/j.heares.2007.12.005

    Article  PubMed  CAS  Google Scholar 

  • Shibata SB, Cortez SR, Beyer LA et al (2010) Transgenic BDNF induces nerve fiber regrowth into the auditory epithelium in deaf cochleae. Exp Neurol 223:464–472. doi:10.1016/j.expneurol.2010.01.011

    Article  PubMed  CAS  Google Scholar 

  • Shinohara T, Bredberg G, Ulfendahl M et al (2002) Neurotrophic factor intervention restores auditory function in deafened animals. Proc Natl Acad Sci U S A 99:1657–1660. doi:10.1073/pnas.032677999

    Article  PubMed  CAS  Google Scholar 

  • Snyder RL, Bonham BH, Sinex DG (2008) Acute changes in frequency responses of inferior colliculus central nucleus (ICC) neurons following progressively enlarged restricted spiral ganglion lesions. Hear Res 246:59–78. doi:10.1016/j.heares.2008.09.010

    Article  PubMed  Google Scholar 

  • Spoendlin H (1969) Innervation patterns in the organ of corti of the cat. Acta Otolaryngol 67:239–254

    Article  PubMed  CAS  Google Scholar 

  • Spoendlin H (1975) Retrograde degeneration of the cochlear nerve. Acta Otolaryngol 79:266–275

    Article  PubMed  CAS  Google Scholar 

  • Spoendlin H (1981) Differentiation of cochlear afferent neurons. Acta Otolaryngol 91:451–456

    Article  PubMed  CAS  Google Scholar 

  • Staecker H, Jolly C, Garnham C (2010) Cochlear implantation: an opportunity for drug development. Drug Discov Today 15:314–321. doi:10.1016/j.drudis.2010.02.005

    Article  PubMed  CAS  Google Scholar 

  • Sugarawara M, Corfas G, Liberman MC (2005) Influence of supporting cells on neuronal degeneration after hair cell loss. JARO 6:136–147. doi:10.1007/s101162-004-5050-1

    Article  Google Scholar 

  • Svirsky MA, Robbins AM, Kirk KI et al (2000) Language development in profoundly deaf children with cochlear implants. Psychol Sci 11:153–158

    Article  PubMed  CAS  Google Scholar 

  • Tessarollo L, Coppola V, Fritzsch B (2004) NT-3 replacement with brain-derived neurotrophic factor redirects vestibular nerve fibers to the cochlea. J Neurosci 24:2575–2584. doi:10.1523/JNEUROSCI.5514-03.2004

    Article  PubMed  CAS  Google Scholar 

  • Warnecke A, Wissel K, Hoffmann A et al (2007) The biological effects of cell-delivered brain-derived neurotrophic factor on cultured spiral ganglion cells. Neuroreport 18:1683–1686. doi:10.1097/WNR.0b013e3282f0b5d7

    Article  PubMed  CAS  Google Scholar 

  • Wefstaedt P, Scheper V, Lenarz T, Stöver T (2005) Brain-derived neurotrophic factor/glial cell line-derived neurotrophic factor survival effects on auditory neurons are not limited by dexamethasone. Neuroreport 16:2011–2014

    Article  PubMed  CAS  Google Scholar 

  • Wise AK, Richardson R, Hardman J et al (2005) Resprouting and survival of guinea pig cochlear neurons in response to the administration of the neurotrophins brain-derived neurotrophic factor and neurotrophin-3. J Comp Neurol 487:147–165. doi:10.1002/cne.20563

    Article  PubMed  CAS  Google Scholar 

  • Wise AK, Hume CR, Flynn BO et al (2010) Effects of localized neurotrophin gene expression on spiral ganglion neuron resprouting in the deafened cochlea. Mol Ther 18:1111–1122. doi:10.1038/mt.2010.28

    Article  PubMed  CAS  Google Scholar 

  • Wise AK, Fallon JB, Neil AJ et al (2011) Combining cell-based therapies and neural prostheses to promote neural survival. Neurotherapeutics 8:774–787. doi:10.1007/s13311-011-0070-0

    Article  PubMed  CAS  Google Scholar 

  • Won JH, Drennan WR, Nie K et al (2011) Acoustic temporal modulation detection and speech perception in cochlear implant listeners. J Acoust Soc Am 130:376–388. doi:10.1121/1.3592521

    Article  PubMed  Google Scholar 

  • Yagi M, Kanzaki S, Kawamoto K et al (2000) Spiral ganglion neurons are protected from degeneration by GDNF gene therapy. J Assoc Res Otolaryngol 1:315–325

    PubMed  CAS  Google Scholar 

  • Yamagata T, Miller JM, Ulfendahl M et al (2004) Delayed neurotrophic treatment preserves nerve survival and electrophysiological responsiveness in neomycin-deafened guinea pigs. J Neurosci Res 78:75–86. doi:10.1002/jnr.20239

    Article  PubMed  CAS  Google Scholar 

  • Yang T, Kersigo J, Jahan I et al (2011) The molecular basis of making spiral ganglion neurons and connecting them to hair cells of the organ of Corti. Hear Res 278:21–33. doi:10.1016/j.heares.2011.03.002

    Article  PubMed  CAS  Google Scholar 

  • Ylikoski J, Pirvola U, Virkkala J et al (1998) Guinea pig auditory neurons are protected by glial cell line-derived growth factor from degeneration after noise trauma. Hear Res 124:17–26

    Article  PubMed  CAS  Google Scholar 

  • Zeng F-G, Rebscher S, Harrison W et al (2008) Cochlear implants: system design, integration, and evaluation. IEEE Rev Biomed Eng 1:115–142. doi:10.1109/RBME.2008.2008250

    Article  PubMed  Google Scholar 

  • Zha XM, Bishop JF, Hansen MR et al (2001) BDNF synthesis in spiral ganglion neurons is constitutive and CREB-dependent. Hear Res 156:53–68

    Article  PubMed  CAS  Google Scholar 

  • Zilberstein Y, Liberman MC, Corfas G (2012) Inner hair cells are not required for survival of spiral ganglion neurons in the adult cochlea. J Neurosci 32(2):405–410. doi:10.1523/JNEUROSCI.4678-11.2012

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The authors thank Chantale Dore for assistance in surgery, care of chronic animals, and measurements of radial nerve fibers; Mr. Larry Ackerman for expert sectioning of the specimens for TEM; and Mr. Paolo Machado for help in the sectioning and counting of the radial nerve fibers. This work was supported by the U.S. National Institutes of Health, the National Institute on Deafness and Other Communication Disorders, Contract #HHS-N-263-2007-00054-C, the Epstein Fund and Hearing Research, Inc., Human recombinant BDNF for these studies was donated by Amgen, Inc., Thousand Oaks, CA.

Author information

Authors and Affiliations

  1. Epstein Hearing Research Laboratory, Department of Otolaryngology–Head and Neck Surgery, University of California San Francisco, 533 Parnassus Ave., Room U490, San Francisco, CA, 94143-0526, USA

    Patricia A. Leake, Olga Stakhovskaya, Alexander Hetherington, Stephen J. Rebscher & Ben Bonham

  2. Department of Hearing and Speech Sciences, University of Maryland, College Park, MD, USA

    Olga Stakhovskaya

Authors
  1. Patricia A. Leake
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Olga Stakhovskaya
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Alexander Hetherington
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Stephen J. Rebscher
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ben Bonham
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Patricia A. Leake.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Leake, P.A., Stakhovskaya, O., Hetherington, A. et al. Effects of Brain-Derived Neurotrophic Factor (BDNF) and Electrical Stimulation on Survival and Function of Cochlear Spiral Ganglion Neurons in Deafened, Developing Cats. JARO 14, 187–211 (2013). https://doi.org/10.1007/s10162-013-0372-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10162-013-0372-5

Keywords

Search

Navigation