title: Late-phase recovery in the cochlear lateral wall following severe degeneration by acute energy failure.
abstract: We previously reported a model of acute cochlear energy failure using a mitochondrial toxin, 3-nitropropionic acid (3-NP), to study mechanisms of inner ear disorders such as inner ear ischemia. In this model, the main cause of hearing loss is apoptosis of fibrocytes in the cochlear lateral wall. Here, we analyzed the time course of structural and hearing level changes in the cochlea from the acute phase to the chronic phase up to 2 months after surgery. Hearing levels as determined by auditory brainstem response (ABR) thresholds exceeded the maximum acoustic output (>87 dBSPL) of the system at all frequencies 1 day after 3-NP treatment. Histology showed nearly complete loss of fibrocytes 2 weeks after 3-NP treatment. However, after 2 months, ABR showed significant recovery at low frequency (8 kHz) in four of five rats treated with 3-NP. ABR thresholds at 20 kHz occasionally showed some recovery. At 40 kHz, recovery of ABR thresholds was not observed. Histology of 3-NP-treated rats revealed partial recovery of the lateral wall and the regenerated fibrocytes in the spiral ligament expressed Na/K-ATPase in the cochlear basal turn 2 months after 3-NP treatment. These results indicate that ABR recovery is caused by regeneration of the cochlear lateral wall. Our findings demonstrate the recoverable capacity of the cochlear lateral wall that leads to functional recovery after severe damage.
authors.affiliation: Laboratory of Auditory Disorders, National Institute of Sensory Organs, National Tokyo Medical Center, Tokyo, Japan.
authors.forename: Kunio
authors.initials: K
authors.lastname: Mizutari
authors.forename: Susumu
authors.initials: S
authors.lastname: Nakagawa
authors.forename: Hideki
authors.initials: H
authors.lastname: Mutai
authors.forename: Masato
authors.initials: M
authors.lastname: Fujii
authors.forename: Kaoru
authors.initials: K
authors.lastname: Ogawa
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Matsunaga
mesh_terms: D000818:Animals; D015834:Cochlear Diseases / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D004195:Disease Models, Animal; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D006319:Hearing Loss, Sensorineural / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D028361:Mitochondrial Diseases / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000502:physiology*; D012720:Severity of Illness Index; D055493:Spiral Ligament of Cochlea / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology