IMPROVED STEROID THERAPY FOR HEARING LOSS

改善听力损失的类固醇治疗

• 批准号: 2752232
• 负责人: DENNIS ROYAL TRUNE
• 金额: $ 6.91万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-12-15 至 2000-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2752232
• 关键词: aldosterone; audiometry; auditory threshold shift; autoimmunity; chemoprevention; ear disorder chemotherapy; electron microscopy; hearing disorders; hormone therapy; immunocytochemistry; laboratory mouse; nonhuman therapy evaluation; prednisolone; sensory disorder chemotherapy

In spite of years of treating various forms of hearing loss with glucocorticoids (prednisone, dexamethasone), there is virtually no clinical or experimental evidence that inflammation of the ear is the underlying etiology. In fact, prednisone therapy is recommended for various sudden and idiopathic hearing disorders for which there is no implication of underlying immune problems. Recent studies from a variety of laboratories have shown that stria vascularis fluid accumulation occurs with autoimmune sensorineural hearing loss, drug ototoxicity, steroid deficiencies, etc. Thus, the common problem is decreased sodium transport by strial cells, leading to edema and failure of the ear to maintain the ionic balances necessary for normal cochlear potentials. The reason glucocorticoids are probably helping in these hearing disorders is that they also have a slight, but significant, effectiveness in increasing sodium transport. If this is the case, there are more effective steroids for sodium transport, the mineralocorticoids. However, these steroids have never been evaluated for improving inner ear function, in spite of the fact that the ear has numerous mineralocorticoid receptors. These findings have led to the hypothesis that mineralcorticoids, such as aldosterone, are more efficient in reversing cochlear dysfunction in these various forms of hearing loss. Thus, the long term objective of this research program is to develop a more effective interventional therapy for diseases on the ear. The general aim of this study is evaluate the effectiveness of mineralcorticoids and glucocorticoids in reversing or preventing the hearing loss. The specific aims of the proposed study are to: Aim 1: To compare the effectiveness of prednisolone and aldosterone in reversing hearing loss once it occurs. Aim 2: To compare the effectiveness of prednisolone and aldosterone in preventing hearing loss. In all studies, assessment of inner ear pathology will be made with auditory brainstem response audiometry, cochlear light and electron microscopy, and hormone and receptor immunohistochemistry of cochlear tissue.

尽管多年来一直在治疗各种形式的听力损失 糖皮质激素（泼尼松、地塞米松），几乎没有 临床或实验证据表明耳朵炎症是 潜在病因学。 事实上，泼尼松疗法被推荐用于 各种突发性和特发性听力障碍，目前尚无治疗方法 潜在免疫问题的影响。最近来自各种研究 的实验室表明，血管纹积液 发生于自身免疫性感音神经性听力损失、药物耳毒性、 类固醇缺乏等。因此，常见的问题是钠减少 通过纹状体细胞运输，导致水肿和耳部功能障碍 维持正常耳蜗电位所需的离子平衡。 糖皮质激素可能对这些听力有帮助的原因 疾病是它们也有轻微但显着的， 增加钠转运的有效性。 如果是这样的话， 有更有效的钠转运类固醇 盐皮质激素。然而，这些类固醇从未被评估过 为了改善内耳功能，尽管事实上耳朵有 许多盐皮质激素受体。这些发现导致 假设盐皮质激素，例如醛固酮，更有效 有效逆转这些不同形式的耳蜗功能障碍 听力损失。 因此，本研究计划的长期目标 旨在针对以下疾病开发更有效的介入治疗方法 耳朵。 本研究的总体目的是评估有效性 盐皮质激素和糖皮质激素在逆转或预防 听力损失。 本研究的具体目标是： 目标 1：比较 泼尼松龙和醛固酮逆转听力损失的有效性 一旦发生。 目标 2：比较泼尼松龙和 醛固酮可预防听力损失。 在所有研究中，内耳病理学评估将通过 听觉脑干反应测听、耳蜗光和电子 耳蜗的显微镜检查以及激素和受体免疫组织化学 组织。