Spiral ganglion cell survival after round window membrane application of brain-derived neurotrophic factor using gelfoam as carrier

Several studies have shown that treatment with various neurotrophins protects spiral ganglion cells (SGCs) from degeneration in hair-cell deprived cochleas. In most of these studies the neurotrophins are delivered by means of intracochlear delivery methods. Recently, other application methods that might be more suited in cochlear implant patients have been developed. We have examined if round window membrane application of gelfoam infiltrated with a neurotrophin resulted in SGC survival in deafened guinea pigs. Two weeks after deafening, gelfoam cubes infiltrated with 6 μg of brain-derived neurotrophic factor (BDNF) were deposited onto the round window membrane of the right cochleas. Electric pulses were delivered through an electrode positioned within the round window niche to electrically evoke auditory brainstem responses (eABRs). Two or four weeks after deposition of the gelfoam all cochleas were histologically examined. We found that local BDNF treatment enhances the survival of SGCs in the basal cochlear turn after two and four weeks. The treatment had no effect on SGC size or shape. In animals treated with BDNF, eABR amplitudes were smaller than in normal-hearing control animals and similar to those in deafened controls. We conclude that BDNF delivered by means of local gelfoam application provides a protective effect, which is limited compared to intracochlear delivery methods.

[1]  H. Silverstein,et al.  Intratympanic Steroid Treatment of Inner Ear Disease and Tinnitus (Preliminary Report) , 1996, Ear, nose, & throat journal.

[2]  R. Altschuler,et al.  Deafferentiation‐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 , 2008, The Journal of comparative neurology.

[3]  Ilmari Pyykkö,et al.  Neurotrophic factor intervention restores auditory function in deafened animals , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[4]  Longitudinal Results With Intratympanic Dexamethasone in the Treatment of Ménière's Disease , 2008, Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology.

[5]  R. Altschuler,et al.  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 , 2007, Journal of neuroscience research.

[6]  A. Salt,et al.  Quantification of solute entry into cochlear perilymph through the round window membrane , 2001, Hearing Research.

[7]  M. Ulfendahl,et al.  Glial cell line-derived neurotrophic factor and antioxidants preserve the electrical responsiveness of the spiral ganglion neurons after experimentally induced deafness , 2008, Neurobiology of Disease.

[8]  G. Bredberg,et al.  Effects of antioxidants on auditory nerve function and survival in deafened guinea pigs , 2007, Neurobiology of Disease.

[9]  K. Kawamoto,et al.  Adenovirus-Mediated Expression of Brain-Derived Neurotrophic Factor Protects Spiral Ganglion Neurons from Ototoxic Damage , 2004, Audiology and Neurotology.

[10]  Bernd Fritzsch,et al.  Making and breaking the innervation of the ear: neurotrophic support during ear development and its clinical implications , 1999, Cell and Tissue Research.

[11]  J. C. de Groot,et al.  An improved fixation method for guinea pig cochlear tissues. , 1987, Acta oto-laryngologica.

[12]  H. Silverstein,et al.  Direct Round Window Membrane Application of Gentamicin in the Treatment of Meniere's Disease , 1997, Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery.

[13]  Rudolf Jaenisch,et al.  Complementary roles of BDNF and NT-3 in vestibular and auditory development , 1995, Neuron.

[14]  A. Salt,et al.  Entry of Substances Into Perilymph Through the Bone of the Otic Capsule After Intratympanic Applications in Guinea Pigs: Implications for Local Drug Delivery in Humans , 2009, Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology.

[15]  R. Hall,et al.  Estimation of surviving spiral ganglion cells in the deaf rat using the electrically evoked auditory brainstem response , 1990, Hearing Research.

[16]  H. Staecker,et al.  Steroid Perfusion of the Inner Ear for Sudden Sensorineural Hearing Loss after Failure of Conventional Therapy: A Pilot Study , 2002, Acta oto-laryngologica.

[17]  G. Smoorenburg,et al.  Reversible cisplatin ototoxicity in the albino guinea pig , 2000, Neuroreport.

[18]  Thomas R. Van De Water,et al.  Brain-derived neurotrophic factor gene therapy prevents spiral ganglion degeneration after hair cell loss , 1998, Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery.

[19]  Bernd Fritzsch,et al.  Neurotrophins in the ear: their roles in sensory neuron survival and fiber guidance. , 2004, Progress in brain research.

[20]  J. Ito,et al.  A New Method for Drug Application to the Inner Ear , 2005, ORL.

[21]  R. Snyder,et al.  Chronic electrical stimulation by a cochlear implant promotes survival of spiral ganglion neurons after neonatal deafness , 1999, The Journal of comparative neurology.

[22]  B Malgrange,et al.  NT‐3 and/or BDNF therapy prevents loss of auditory neurons following loss of hair cells , 1996, Neuroreport.

[23]  Robert K Shepherd,et al.  Deafness alters auditory nerve fibre responses to cochlear implant stimulation , 2007, The European journal of neuroscience.

[24]  Barbara Canlon,et al.  Protection of auditory neurons from aminoglycoside toxicity by neurotrophin-3 , 1996, Nature Medicine.

[25]  M. Paparella,et al.  Meniere's disease , 2008, The Lancet.

[26]  M. Ulfendahl,et al.  Middle Ear Application of a Sodium Hyaluronate Gel Loaded with Neomycin in a Guinea Pig Model , 2009, Ear and hearing.

[27]  Y. Raphael,et al.  Effects of chronic high-rate electrical stimulation on the cochlea and eighth nerve in the deafened guinea pig , 1997, Hearing Research.

[28]  Sally L. Gewalt,et al.  Quantitative anatomy of the round window and cochlear aqueduct in guinea pigs , 2001, Hearing Research.

[29]  Robert K Shepherd,et al.  Exogenous BDNF Rescues Rat Spiral Ganglion Neurons In Vivo , 2005, Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology.

[30]  L. Gillespie,et al.  Delayed neurotrophin treatment supports auditory neuron survival in deaf guinea pigs , 2004, Neuroreport.

[31]  H. Versnel,et al.  Time course of cochlear electrophysiology and morphology after combined administration of kanamycin and furosemide , 2007, Hearing Research.

[32]  A. Lalwani,et al.  In Vitro and In Vivo Assessment of the Ability of Adeno‐Associated Virus–Brain‐Derived Neurotrophic Factor to Enhance Spiral Ganglion Cell Survival Following Ototoxic Insult , 2002, The Laryngoscope.

[33]  H. Versnel,et al.  Morphological changes in spiral ganglion cells after intracochlear application of brain-derived neurotrophic factor in deafened guinea pigs , 2008, Hearing Research.

[34]  A. Salt,et al.  Principles of Local Drug Delivery to the Inner Ear , 2009, Audiology and Neurotology.

[35]  Jean Caston,et al.  Salicylate Induces Tinnitus through Activation of Cochlear NMDA Receptors , 2003, The Journal of Neuroscience.

[36]  A. Wise,et al.  A single dose of neurotrophin-3 to the cochlea surrounds spiral ganglion neurons and provides trophic support , 2005, Hearing Research.

[37]  F. B. Simmons,et al.  Estimating Eighth Nerve Survival by Electrical Stimulation , 1983, The Annals of otology, rhinology, and laryngology.

[38]  Ramón Hinojosa-González,et al.  Dexamethasone Inner Ear Perfusion by Intratympanic Injection in Unilateral Ménière's Disease: A Two-year Prospective, Placebo-Controlled, Double-blind, Randomized Trial , 2005, Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery.

[39]  Andrew K. Wise,et al.  Neurotrophic Factors and Neural Prostheses: Potential Clinical Applications Based Upon Findings in the Auditory System , 2007, IEEE Transactions on Biomedical Engineering.

[40]  Stephanie B. Epp,et al.  Chronic depolarization enhances the trophic effects of brain‐derived neurotrophic factor in rescuing auditory neurons following a sensorineural hearing loss , 2005, The Journal of comparative neurology.

[41]  Lisa N Gillespie,et al.  BDNF‐induced survival of auditory neurons in vivo: Cessation of treatment leads to accelerated loss of survival effects , 2003, Journal of neuroscience research.

[42]  T. Stöver,et al.  Effects of delayed treatment with combined GDNF and continuous electrical stimulation on spiral ganglion cell survival in deafened guinea pigs , 2009, Journal of neuroscience research.

[43]  Donald L. Swiderski,et al.  Cochlear implants and ex vivo BDNF gene therapy protect spiral ganglion neurons , 2007, Hearing Research.

[44]  Paul Kruszka,et al.  Neurotrophins can enhance spiral ganglion cell survival after inner hair cell loss , 1997, International Journal of Developmental Neuroscience.

[45]  G. Bredberg,et al.  Delayed neurotrophic treatment preserves nerve survival and electrophysiological responsiveness in neomycin‐deafened guinea pigs , 2004, Journal of neuroscience research.

[46]  Marcos V. Goycoolea,et al.  Round window membrane. Structure function and permeability: A review , 1997, Microscopy research and technique.

[47]  S. O'Leary,et al.  Inner Ear Therapy for Neural Preservation , 2006, Audiology and Neurotology.

[48]  A. Wise,et al.  Resprouting and survival of guinea pig cochlear neurons in response to the administration of the neurotrophins brain‐derived neurotrophic factor and neurotrophin‐3 , 2005, The Journal of comparative neurology.

[49]  Juichi Ito,et al.  Novel Strategy for Treatment of Inner Ears using a Biodegradable Gel , 2005, The Laryngoscope.

[50]  P. Stypulkowski,et al.  Single fiber mapping of spatial excitation patterns in the electrically stimulated auditory nerve , 1987, Hearing Research.

[51]  L. Fisher,et al.  Intratympanic Steroid Injection for Treatment of Idiopathic Sudden Hearing Loss , 2005, Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery.

[52]  R E Brummett,et al.  Interaction of kanamycin and ethacrynic acid. Severe cochlear damage in guinea pigs. , 1973, Archives of otolaryngology.

[53]  Martijn J. H. Agterberg,et al.  Enhanced Survival of Spiral Ganglion Cells After Cessation of Treatment with Brain-Derived Neurotrophic Factor in Deafened Guinea Pigs , 2009, Journal of the Association for Research in Otolaryngology.

[54]  Jeffrey T Borenstein,et al.  Drug Delivery for Treatment of Inner Ear Disease: Current State of Knowledge , 2010, Ear and hearing.

[55]  Y. Raphael,et al.  Over-expression of BDNF by adenovirus with concurrent electrical stimulation improves cochlear implant thresholds and survival of auditory neurons , 2008, Hearing Research.

[56]  Stephen O'Leary,et al.  Delivery of Neurotrophin-3 to the Cochlea using Alginate Beads , 2005, Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology.

[57]  Gordon G Wallace,et al.  Polypyrrole-coated electrodes for the delivery of charge and neurotrophins to cochlear neurons. , 2009, Biomaterials.