Electrophysiological assessment and pharmacological treatment of blast-induced tinnitus.

Autor: Lu J; Hough Ear Institute, Oklahoma City, Oklahoma, United States of America., West MB; Hough Ear Institute, Oklahoma City, Oklahoma, United States of America., Du X; Hough Ear Institute, Oklahoma City, Oklahoma, United States of America., Cai Q; Hough Ear Institute, Oklahoma City, Oklahoma, United States of America., Ewert DL; Hough Ear Institute, Oklahoma City, Oklahoma, United States of America., Cheng W; Hough Ear Institute, Oklahoma City, Oklahoma, United States of America., Nakmali D; Hough Ear Institute, Oklahoma City, Oklahoma, United States of America., Li W; Hough Ear Institute, Oklahoma City, Oklahoma, United States of America., Huang X; Hough Ear Institute, Oklahoma City, Oklahoma, United States of America., Kopke RD; Hough Ear Institute, Oklahoma City, Oklahoma, United States of America.; Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, United States of America.; Departments of Physiology and Otolaryngology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States of America.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2021 Jan 07; Vol. 16 (1), pp. e0243903. Date of Electronic Publication: 2021 Jan 07 (Print Publication: 2021).
DOI: 10.1371/journal.pone.0243903
Abstrakt: Tinnitus, the phantom perception of sound, often occurs as a clinical sequela of auditory traumas. In an effort to develop an objective test and therapeutic approach for tinnitus, the present study was performed in blast-exposed rats and focused on measurements of auditory brainstem responses (ABRs), prepulse inhibition of the acoustic startle response, and presynaptic ribbon densities on cochlear inner hair cells (IHCs). Although the exact mechanism is unknown, the "central gain theory" posits that tinnitus is a perceptual indicator of abnormal increases in the gain (or neural amplification) of the central auditory system to compensate for peripheral loss of sensory input from the cochlea. Our data from vehicle-treated rats supports this rationale; namely, blast-induced cochlear synaptopathy correlated with imbalanced elevations in the ratio of centrally-derived ABR wave V amplitudes to peripherally-derived wave I amplitudes, resulting in behavioral evidence of tinnitus. Logistic regression modeling demonstrated that the ABR wave V/I amplitude ratio served as a reliable metric for objectively identifying tinnitus. Furthermore, histopathological examinations in blast-exposed rats revealed tinnitus-related changes in the expression patterns of key plasticity factors in the central auditory pathway, including chronic loss of Arc/Arg3.1 mobilization. Using a formulation of N-acetylcysteine (NAC) and disodium 2,4-disulfophenyl-N-tert-butylnitrone (HPN-07) as a therapeutic for addressing blast-induced neurodegeneration, we measured a significant treatment effect on preservation or restoration of IHC ribbon synapses, normalization of ABR wave V/I amplitude ratios, and reduced behavioral evidence of tinnitus in blast-exposed rats, all of which accorded with mitigated histopathological evidence of tinnitus-related neuropathy and maladaptive neuroplasticity.
Competing Interests: The authors have read the journal’s policy, and the authors of this manuscript have the following competing interests to declare: RDK is a minor stockholder in Otologic Pharmaceutics Inc. The authors would like to declare the following patents/patent applications associated with this research: Patent families 10,555,915; 9,289,404; 10,111,843. The authors also declare the following product in development associated with this research: an oral combination drug (NAC plus HPN-07) being developed for prevention and/or treatment of acute sensorineural hearing loss. This does not alter our adherence to PLOS ONE policies on sharing data and materials.
Databáze: MEDLINE
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