IMPROVED STEROID THERAPY FOR HEARING LOSS

尽管多年来治疗各种听力损失

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.