# Efficacy and Mechanisms of Mild Therapeutic Hypothermia for Hearing Preservation from NIHL

> **NIH NIH F31** · UNIVERSITY OF MIAMI CORAL GABLES · 2021 · $46,036

## Abstract

Project Summary
Noise-induced hearing loss (NIHL) caused by exposure to intense or repeated noise results in damage to the sensitive
structures within the cochlea. NIHL has become one of the leading occupational and recreational hazards afflicting nearly
40 million Americans. NIHL is also a serious concern for our military, and overall results in a high economic burden due
to worker compensation and veteran disability. Although many treatments have been proposed to mitigate NIHL with
promising results in preclinical studies, there are still no FDA-approved treatments for NIHL. Mild therapeutic hypothermia
(30-33 °C) has been extensively studied as a neuroprotective strategy against various types of neurological traumas because
of its ability to mediate various injury responses to trauma including oxidative stress, apoptosis, and inflammation. We aim
to assess the therapeutic benefit of localized therapeutic hypothermia in mitigation of cochlear injury following acoustic
trauma in a rodent model. In this proposal, we seek to engineer a novel non-invasive device used to induce localized mild
therapeutic hypothermia post-NIHL and assess long-term functional hearing and cochlear neural substrate preservation. Our
preliminary results suggest that controlled and localized therapeutic hypothermia provided to the inner ear post-NIHL
significantly lowers hearing threshold shifts in hypothermia-treated animals when compared to normothermic control
animals. Furthermore, we observe reduced cochlear synaptopathology with therapeutic hypothermia. To determine
protective mechanisms underlying hypothermia, we will identify molecular pathways and gene networks that are regulated
by temperature post-NIHL. A detailed characterization of the pathways in a relevant rodent model will provide future
opportunities to identify additional synergistic otoprotective targets. Based on preliminary results, our primary mechanistic
emphases will be on caspase-dependent apoptotic pathways and inflammatory responses with activated macrophage
recruitment and expression. In the long-term, we aim to address the limited therapeutic options for NIHL that may be
extended to various otological traumas, including blast-induced hearing loss or surgically-induced hearing loss.

## Key facts

- **NIH application ID:** 10069994
- **Project number:** 5F31DC018212-02
- **Recipient organization:** UNIVERSITY OF MIAMI CORAL GABLES
- **Principal Investigator:** Samantha Rincon Sabatino
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $46,036
- **Award type:** 5
- **Project period:** 2020-01-09 → 2023-11-08

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10069994

## Citation

> US National Institutes of Health, RePORTER application 10069994, Efficacy and Mechanisms of Mild Therapeutic Hypothermia for Hearing Preservation from NIHL (5F31DC018212-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10069994. Licensed CC0.

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