# Therapeutic Assessment of TrkB Agonist in a Unilateral Blast-Induced Hearing Loss Mouse Model

## TL;DR

This study shows that a drug called 7,8-DHF can help mice recover from hearing loss caused by blast injuries, suggesting it might be useful for treating similar injuries in humans.

## Contribution

The study demonstrates the therapeutic potential of a TrkB agonist in a novel mouse model of blast-induced hearing loss.

## Key findings

- 7,8-DHF treatment significantly reduced hearing loss in both ears of mice after blast exposure.
- Improvement in hearing thresholds was observed as early as one week post-blast in the unexposed ear.
- Recovery plateaued after four weeks, indicating partial but significant auditory function restoration.

## Abstract

Background/Objectives: Blast-induced hearing loss (BIHL) is a major concern, particularly for military personnel, and is linked to impaired auditory neuron survival and synaptic plasticity. This study investigates the potential of the TrkB agonist 7,8-dihydroxyflavone (7,8-DHF) to reduce the severity of BIHL and promote recovery in a mouse model. Methods: Eight-week-old male C57BL/6J mice were used. A custom-built, compressed air-driven system utilizing a modified paintball apparatus was employed to deliver controlled unilateral double blasts (~22 psi exposure pressure) to the left ear. The blasts were administered 30 min apart. Immediately following the second blast, mice received either 7,8-DHF (10 mg/kg) or vehicle (10% DMSO) via intraperitoneal injection. Auditory brainstem responses (ABRs) were measured in both ears at baseline (pre-blast) and at several post-exposure time points. Results: The consecutive blast exposure induced a significant elevation in ABR thresholds, indicative of hearing loss, in both the ipsilateral (exposed) and contralateral (unexposed) ears of vehicle-treated mice. Notably, mice treated with 7,8-DHF demonstrated a marked improvement in hearing recovery compared to the vehicle group. Significant reductions in ABR thresholds were observed in the ipsilateral ear at 4 weeks post-blast (p < 0.0001) and in the contralateral ear as early as 1-week post-blast (p = 0.0236). However, the recovery was partial, with ABR thresholds plateauing after 4 weeks. Conclusions: A controlled blast model demonstrates that systemic administration of the TrkB agonist 7,8-DHF exerts a protective effect, partially restoring auditory function after blast injury. This supports the therapeutic potential of targeting the BDNF-TrkB signaling pathway for managing BIHL.