Application of mild therapeutic hypothermia for hearing conservation during cochlear implant surgeries

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Project Summary More than half a million patients, including children, have benefitted from the remarkable technological breakthrough that are cochlear implants (CI). An increasing number of patients have some level of residual hearing at the time of implantation and can benefit from bimodal electro-acoustic devices. Surviving hair cell activity and as a result a functioning organ of Corti and neural substrate has recently been linked to speech perception outcomes. However, trauma during implantation leads to inflammation and oxidative stress that can exacerbate residual hearing loss. Successful translation of therapeutic interventions to limit pathophysiology of the injury have yet to be achieved. The present work will design and implement applications of localized, therapeutic hypothermia for protection of hair cells and neural substrate following CI. The specific aims are motivated by preliminary and published data showing that localized, mild hypothermia delivered to the cochlea is highly effective and safe, protecting hair cells and synaptic components, protecting the integrity of the cochlear blood-labyrinth barrier and preserving residual hearing long-term after implantation. Specific aim 1 will test safety and efficacy of cooling when applied to the cochlea and develop an optimal protocol for improved long-term functional and physiological outcomes. In specific aim 2 using molecular biology and immunohistochemistry techniques we will define the neuroprotective mechanisms underlying hypothermia. Combining the preclinical results with human cadaver temporal bone studies in specific aim 3, we will develop a device and system for human application. The system will enable delivery of optimized hypothermia therapy for residual structure and functional protection post-implant. Ensuring the survival of sensitive hair cells and neural structures in the cochlea are likely to lead to improved speech perception outcomes and will enable patients to benefit from future technologies and/or therapies. The results from this project can be further extended to other inner ear-related trauma such as ototoxicity, or noise- and blast-induced trauma.