Preventing Ototoxic Synergy of Prior Noise Trauma during Aminoglycoside Therapy
Abstract
Candidate aminoglycoside channels (e.g. TRPV1) and their regulating components in the inner ear, control hearing sensitivity in a characteristic fashion. Our newly acquired data suggested the neurotransmission between the inner hair cell and the spiral ganglion neuron is a major ototoxic target. We first confirmed that noise exposure modifies this neural transmission adversely and discovered that the deficiency of TRPV1 alleviated such cochlear synaptopathy. Meanwhile, TRPV1 does not involved in a protective adaptation process in the cochlea. Next, we found that noise exposure or potentially aminoglycoside treatment resulted in cochlear inflammation, manifested by abnormal ribbon synaptic rearrangement or reduction of ribbon density. Thus, how prior noise exposure and aminoglycoside-induced ototoxicity interplay at this pivotal functional region of neurotransmission is open question in auditory research, and needless to say, very relevant to personals in military settings. In summary, we are a step closer to the goal of this project, to search countermeasures to prevent aminoglycoside-induced cochleotoxicity (as well as vestibulotoxicity and nephrotoxicity) that can severely debilitate the recovery of military personnel, as well as civilians received aminoglycoside therapy with a history of (or likely ongoing) acoustic insult.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2018
- Accession Number
- AD1059210
Entities
People
- Hongzhe Li
Organizations
- Jerry L. Pettis Memorial VA Medical Center