Mild Therapeutic Hypothermia and Putative Mechanisms of Hair Cell Survival in the Cochlea.

Significance: Sensorineural hearing loss has significant implications for quality of life and risk for comorbidities such as cognitive decline. Noise and ototoxic drugs represent two common risk factors for acquired hearing loss that are potentially preventable. Recent Advances: Numerous otoprotection strategies have been postulated over the past four decades with primary targets of upstream redox pathways. More recently, the application of mild therapeutic hypothermia (TH) has shown promise for otoprotection for multiple forms of acquired hearing loss. Critical Issues: Systemic antioxidant therapy may have limited application for certain ototoxic drugs with a therapeutic effect on redox pathways and diminished efficacy of the primary drug's therapeutic function (e.g., cisplatin for tumors). Future Directions: Mild TH likely targets multiple mechanisms, contributing to otoprotection, including slowed metabolics, reduced oxidative stress, and involvement of cold shock proteins. Further work is needed to identify the mechanisms of mild TH at play for various forms of acquired hearing loss.