The primary goal of this project is to describe our current understanding of the oxidant hypothesis of noise and drug-induced hearing loss and show how this process translates into cochlear inflammation. Basic cellular mechanisms underlying the contribution of oxidant stress to hearing loss will be explained and molecular pathways leading to inflammatory processes will be outlined. Several different aspects of the cochlear inflammatory process will be discussed in detail. These include the sources of inflammatory cells, chemokines, inflammatory cytokines and the roles of cochlear resident immune cells in mediating hearing loss. In addition, evidence for a robust cochlear-based steroid axis which is activated by cochlear stress and serves a protective system. The role of the strial vasculature networks which aid in maintenance of the blood-labyrinth barrier and control the entry of circulating immune cells into the cochlea will be described. Molecular pathwaysleading to activation of the local inflammatory process will be highlighted and otoprotective treatment options will be discussed. The relevance of certain clinically used anti-inflammatory interventions, such as trans-tympanic steroids and other drugs will also be discussed. Furthermore, we will examine recent patents focusing on the use of anti-inflammatory agents for the treatment of drug and noise-induced hearing loss.

Preface.- The Cochlea.- Oxidative Stress and Hearing Loss.- Corticotropin Releasing Factor Signaling in the Mammalian Cochlea: An Integrative Niche for Cochlear Homeostatic Balance Against Noise.- Cochlear vascular pathology and hearing loss.- Cochlear Inflammation Associated with Noise-Exposure.- Middle Ear Infection and Hearing Loss.- Inflammation potentiates cochlear uptake of ototoxins and drug-induced hearing loss.- The Contribution of Anti-Oxidant and Anti-Inflammatory Functions of Adenosine A1 Receptor In Mediating Otoprotection.- Anti-inflammatory therapies for sensorineural hearing loss.- Implementation and Outcomes of Clinical Trials in Immune-Mediated Hearing Loss and other Rare Diseases.- Index.