title: Balance dysfunction resulting from acute inner ear energy failure is caused primarily by vestibular hair cell damage.
abstract: Inner ear energy failure is associated with disorders such as inner ear ischemia. Recently, we used the mitochondrial toxin 3-nitropropionic acid (3-NP) to establish an animal model of inner ear energy failure that presents with auditory dysfunction. Here we investigated the mechanisms underlying balance disorders in the 3-NP animal model. Spontaneous nystagmus peaked 6 hr after treatment with either 300 mM or 500 mM 3-NP. The nystagmus attenuated gradually and disappeared 3 days after 3-NP treatment. A caloric test using ice water was performed to evaluate residual vestibular function 7 days after 3-NP treatment. The response to caloric stimulation was reduced to approximately 40% of the response of the untreated ear following 300 mM 3-NP and was undetectable following 500 mM 3-NP. Structural changes in the peripheral vestibular organs were analyzed by light and electron microscopy. Severe loss of stereocilia was observed following 500 mM 3-NP, whereas disorganized and mildly reduced stereocilia were observed following 300 mM 3-NP. There was severe loss and degeneration of vestibular hair cells following 500 mM 3-NP but only slight loss and degeneration of hair cells following 300 mM 3-NP. These results indicate that acute inner ear energy failure causes balance dysfunction mainly by damaging hair cells in the vestibule, which is distinct from the mechanism underlying auditory disorders.
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: Masato
authors.initials: M
authors.lastname: Fujioka
authors.forename: Susumu
authors.initials: S
authors.lastname: Nakagawa
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; D002150:Caloric Tests; D003051:Cochlea / Q000473:pathology / Q000503:physiopathology / Q000648:ultrastructure; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D018069:Hair Cells, Vestibular / Q000473:pathology / Q000502:physiology* / Q000648:ultrastructure; D007759:Labyrinth Diseases / Q000139:chemically induced / Q000150:complications / Q000503:physiopathology*; D008297:Male; D008854:Microscopy, Electron; D009410:Nerve Degeneration / Q000139:chemically induced / Q000209:etiology / Q000503:physiopathology; D009498:Neurotoxins / Q000008:administration & dosage / Q000633:toxicity; D009574:Nitro Compounds / Q000008:administration & dosage / Q000633:toxicity; D009759:Nystagmus, Pathologic / Q000139:chemically induced / Q000209:etiology / Q000503:physiopathology; D009925:Organ of Corti / Q000473:pathology / Q000503:physiopathology / Q000648:ultrastructure; D004856:Postural Balance / Q000502:physiology*; D011422:Propionates / Q000008:administration & dosage / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D015837:Vestibular Diseases / Q000139:chemically induced / Q000209:etiology / Q000503:physiopathology*
chemical_list: D009498:Neurotoxins; D009574:Nitro Compounds; D011422:Propionates; C015392:3-nitropropionic acid