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Prevention or reversal of sensorineural hearing loss (SNHL) through biologic mechanisms

机译:通过生物机制预防或逆转感觉神经性听力损失(SNHL)

摘要

The invention is accomplished by preventing and/or reversing inner ear damage due to noise or toxins. In part, this is accomplished by upregulating antioxidant enzyme activity by applying agents such as R-N6-Phenylisopropyl adenosine (R-PIA) to the round window membrane of the inner ear or systemically, and/or by also applying agents such as 1-2-oxothiazolidine-4-carboxylic acid (Procysteine) to the round window membrane. Also, the invention is accomplished by giving the compounds systemically. Selective auditory hair cell protection in the face of gentamicin exposure by concomitant delivery of an NMDA antagonist or glial derived neurotrophic factor (GDNF) with the gentamicin. These and additional agents are also accomplished by curtailing activated programmed cell death pathways and/or inducing/enhancing cell repair mechanisms in the inner ear. The agent (s) may be applied before, during or after the noise trauma or toxin exposure.
机译:通过防止和/或逆转由于噪音或毒素造成的内耳损伤来实现本发明。这部分是通过以下方式实现的:通过将诸如R-N6-苯基异丙基腺苷(R-PIA)之类的试剂施加到内耳的圆窗膜上或全身性地上调抗氧化酶的活性,和/或还通过施加诸如1-将2-氧噻唑烷-4-羧酸(半胱氨酸)置于圆窗膜上。同样,通过系统地给出化合物来完成本发明。通过与庆大霉素同时递送NMDA拮抗剂或神经胶质衍生的神经营养因子(GDNF),在庆大霉素暴露下选择性听觉毛细胞保护。这些和其他药剂也可通过减少内耳中激活的程序性细胞死亡途径和/或诱导/增强细胞修复机制来实现。可以在噪声创伤或毒素暴露之前,之中或之后施用所述试剂。

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