Laboratory of Auditory Disorders, National Institute of Sensory Organs, National Tokyo Medical Center, Tokyo, Japan.
J Neurosci Res. 2010 May 1;88(6):1262-72. doi: 10.1002/jnr.22289.
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.
内耳能量衰竭与内耳缺血等疾病有关。最近，我们使用线粒体毒素 3-硝基丙酸（3-NP）建立了内耳能量衰竭动物模型，该模型表现出听觉功能障碍。在这里，我们研究了 3-NP 动物模型中平衡障碍的机制。自发眼球震颤在接受 300mM 或 500mM 3-NP 治疗后 6 小时达到峰值。眼球震颤逐渐减弱，在 3-NP 治疗后 3 天消失。在 3-NP 治疗后 7 天使用冰水进行冷刺激试验以评估残余前庭功能。300mM 3-NP 后，对冷刺激的反应降低到未处理耳的约 40%，而 500mM 3-NP 后则无法检测到。通过光镜和电镜分析外周前庭器官的结构变化。500mM 3-NP 后观察到严重的静纤毛缺失，而 300mM 3-NP 后观察到静纤毛排列紊乱和轻度减少。500mM 3-NP 后前庭毛细胞严重丢失和变性，而 300mM 3-NP 后仅轻微丢失和变性。这些结果表明，急性内耳能量衰竭主要通过损伤前庭中的毛细胞引起平衡功能障碍，这与听觉障碍的机制不同。
