This Program Project consists of four integrated projects that explore the mechanisms, functional consequences, and prevention of cochlear damage/hearing loss induced by ototoxic drugs and acoustic over- stimulation. In addition to its basic scientific merit, the project has clinical implications with regard to acquired hearing loss (HL) in humans. The clinical motivations for Projects 1 and 2 are (a) a growing awareness that inner hair cell (IHC) loss may underlie many of the perceptual difficulties experienced by people with acquired HL, and (b) a lack of clinical tools for assessing IHC loss. Clinical motivations for Projects 3 and 4 include observations that (a) susceptibility to HL varies tremendously among individuals, and (b) identification of the factors that contribute to susceptibility may be crucial for preventing acquired HL in the future. All four projects utilize the chinchilla, a mammal whose hearing capabilities are similar to humans. Project 1 examines anatomical, physiological, and behavioral changes associated with selected IHC lesions produced by carboplatin, an anti-cancer drug. Project 2 uses auditory evoked potentials to examine functional changes along the auditory neuroaxis associated with permanent IHC loss from carboplatin and transient cochlear deafferentation by kainic acid, a glutamate analog. Project 3 explores acoustic and biochemical methods of protecting the cochlea from hearing loss induced by acoustic over-stimulation and carboplatin. Project 4 focuses on potential protective effects on lateral and medial olivocochlear efferent fibers on hair cell loss and hearing loss induced by carboplatin, aminoglycosides, kainic acid and acoustic over-stimulation. Overlapping themes among the projects include consequences of IHC loss, central nervous system reorganization, mechanisms of ototoxic damage, and strategies for protecting the inner ear from damage.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Program Projects (P01)
Project #
3P01DC003600-02S1
Application #
6222739
Study Section
Special Emphasis Panel (ZDC1 (12))
Program Officer
Donahue, Amy
Project Start
1999-01-01
Project End
2003-12-31
Budget Start
2000-02-01
Budget End
2000-12-31
Support Year
2
Fiscal Year
2000
Total Cost
$20,000
Indirect Cost
Name
State University of New York at Buffalo
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
038633251
City
Buffalo
State
NY
Country
United States
Zip Code
14260
Fetoni, Anna R; Bielefeld, Eric C; Paludetti, Gaetano et al. (2014) A putative role of p53 pathway against impulse noise induced damage as demonstrated by protection with pifithrin-alpha and a Src inhibitor. Neurosci Res 81-82:30-7
Cowper-Smith, C D; Dingle, R N; Guo, Y et al. (2010) Synchronous auditory nerve activity in the carboplatin-chinchilla model of auditory neuropathy. J Acoust Soc Am 128:EL56-62
McNerney, Kathleen M; Burkard, Robert F (2010) The effects of a second stimulus on the auditory steady state response (ASSR) from the inferior colliculus of the chinchilla. Int J Audiol 49:561-73
El-Badry, Mohamed M; McFadden, Sandra L (2009) Evaluation of inner hair cell and nerve fiber loss as sufficient pathologies underlying auditory neuropathy. Hear Res 255:84-90
El-Badry, Mohamed M; McFadden, Sandra L (2007) Electrophysiological correlates of progressive sensorineural pathology in carboplatin-treated chinchillas. Brain Res 1134:122-30
Hu, Bo Hua; Henderson, Donald; Nicotera, Thomas M (2006) Extremely rapid induction of outer hair cell apoptosis in the chinchilla cochlea following exposure to impulse noise. Hear Res 211:16-25
Sun, Wei; Mercado 3rd, Eduardo; Wang, Ping et al. (2005) Changes in NMDA receptor expression in auditory cortex after learning. Neurosci Lett 374:63-8
Godfrey, Donald A; Godfrey, Matthew A; Ding, Da-Lian et al. (2005) Amino acid concentrations in chinchilla cochlear nucleus at different times after carboplatin treatment. Hear Res 206:64-73
Bielefeld, Eric C; Hynes, Sarah; Pryznosch, David et al. (2005) A comparison of the protective effects of systemic administration of a pro-glutathione drug and a Src-PTK inhibitor against noise-induced hearing loss. Noise Health 7:24-30
Szalda, Kathleen; Burkard, Robert (2005) The effects of nembutal anesthesia on the auditory steady-state response (ASSR) from the inferior colliculus and auditory cortex of the chinchilla. Hear Res 203:32-44

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