Balance dysfunction resulting from acute inner ear energy failure is caused primarily by vestibular hair cell damage.
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.
Mizutari
Kunio
K
Laboratory of Auditory Disorders, National Institute of Sensory Organs, National Tokyo Medical Center, Tokyo, Japan.
Fujioka
Masato
M
Nakagawa
Susumu
S
Fujii
Masato
M
Ogawa
Kaoru
K
Matsunaga
Tatsuo
T
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*
D009498:Neurotoxins; D009574:Nitro Compounds; D011422:Propionates; C015392:3-nitropropionic acid