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Novel Methods to Promote Survival and Regeneration of the Auditory Nerve and Improve Cochlear Implant Function.

dc.contributor.authorChikar, Jennifer Annen_US
dc.date.accessioned2009-05-15T15:11:33Z
dc.date.availableNO_RESTRICTIONen_US
dc.date.available2009-05-15T15:11:33Z
dc.date.issued2009en_US
dc.date.submitteden_US
dc.identifier.urihttps://hdl.handle.net/2027.42/62248
dc.description.abstractA principal cause of sensorineural hearing loss is injury to or loss of cochlear hair cells, which are critical components of sound transduction. These auditory hair cells do not naturally regenerate in mammals. Loss of hair cells often leads to a degeneration of the processes that innervate them along with the ganglion cell bodies of the auditory nerve. The only currently accepted treatment for hearing loss of this type is the cochlear implant, an auditory prosthesis that has been in clinical use for over 30 years. While the cochlear implant has been successful in providing or restoring hearing to over 100,000 patients, there are limitations to the hearing provided by the implant, particularly for complex sounds such as speech in noise and music. The peripheral processes and ganglion cell bodies receive and process the electrical stimulation from the implant, and thus the survival of these components of the auditory nerve is critical to the perception of sound from the cochlear implant. This dissertation presents two novel methods of promoting auditory nerve survival and regrowth following hair cell loss. The first method used an adenoviral construct containing a gene insert for brain – derived neurotrophic factor, designed to increase endogenous production of this growth factor. The introduction of this adenovirus into the cochlea led to a decrease in electrophysiological and psychophysical thresholds to cochlear implant stimulation and promoted long – term ganglion cell survival. This study was unique in addressing the psychophysical effects of the anatomical changes induced by growth factor treatment. In the second method, a specialized implant coating was designed to attract growth of peripheral processes to make contact with a cochlear implant in vivo. In this study, a new histological technique was developed, which allowed visualization of peripheral processes and evaluation of their spatial relationship with an implant. This coating attracted significant neuronal growth in close proximity to the implant and decreased the impedance between implant electrodes. These studies together demonstrate the significant plasticity of the auditory nerve to survive following deafness, and indicate the potential for nerve regeneration efforts to improve cochlear implant performance.en_US
dc.format.extent23399910 bytes
dc.format.extent1373 bytes
dc.format.mimetypeapplication/pdf
dc.format.mimetypetext/plain
dc.language.isoen_USen_US
dc.subjectCochlear Implanten_US
dc.subjectNerve Regenerationen_US
dc.subjectPsychophysicsen_US
dc.subjectEABRen_US
dc.subjectImmunohistochemistryen_US
dc.subjectSpiral Ganglion Cellen_US
dc.titleNovel Methods to Promote Survival and Regeneration of the Auditory Nerve and Improve Cochlear Implant Function.en_US
dc.typeThesisen_US
dc.description.thesisdegreenamePhDen_US
dc.description.thesisdegreedisciplineNeuroscienceen_US
dc.description.thesisdegreegrantorUniversity of Michigan, Horace H. Rackham School of Graduate Studiesen_US
dc.contributor.committeememberPfingst, Bryan E.en_US
dc.contributor.committeememberRaphael, Yehoashen_US
dc.contributor.committeememberAltschuler, Richard A.en_US
dc.contributor.committeememberMartin, David C.en_US
dc.contributor.committeememberMiller, Josef M.en_US
dc.subject.hlbtoplevelScienceen_US
dc.description.bitstreamurlhttp://deepblue.lib.umich.edu/bitstream/2027.42/62248/1/jchikar_1.pdf
dc.owningcollnameDissertations and Theses (Ph.D. and Master's)


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