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

PMID: 41874069 · DOI: 10.3390/audiolres16020036 · Audiology research, 2026 · Sung Kyun Kim, Han-Gyu Bae, Jun Hee Kim
📄 Abstract

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. 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. 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 ( 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.

Confidence: 0.27 · 13 полей извлечено
Идентификация (6 полей)
Target
TrkB
1.00
Alt. target
Tropomyosin receptor kinase B
1.00
Protein family
Tropomyosin receptor kinase
0.90
Functional class
Receptor tyrosine kinase
0.90
Subcellular loc.
0.00
Isoforms (metab/obesity)
0.00
Механизм действия (21 полей)
Mechanism
TrkB agonist
0.95
Mutations (obesity/lean)
0.00
Activity (obesity)
0.00
Activity temporal
0.00
Energy balance
0.00
Appetite
0.00
Fat metabolism
0.00
Lipolysis
0.00
Thermogenesis
0.00
Muscle metabolism
0.00
Inflammation
0.00
Glucose metabolism
0.00
AA metabolism
0.00
Hormonal pathways
0.00
Cell death
0.00
Adipocyte fibrosis
0.00
Upstream (biochem)
0.00
Upstream (physiol)
0.00
Downstream (biochem)
0.00
Downstream (physiol)
0.00
PTMs
0.00
Экспрессия (8 полей)
Tissue expression
0.00
In vitro
0.00
In vivo
The study investigates the potential of the TrkB agonist 7,8-dihydroxyflavone (7,8-DHF) to reduce the severity of blast-induced hearing loss and promote recovery in a mouse model. Eight-week-old male C57BL/6J mice were used. A custom-built, compressed air-driven system delivered controlled unilateral double blasts to the left ear. Immediately after 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 at baseline and post-exposure. Mice treated with 7,8-DHF demonstrated marked improvement in hearing recovery compared to vehicle, with significant reductions in ABR thresholds in the ipsilateral ear at 4 weeks post-blast.
1.00
In silico
0.00
Genetic association
0.00
Ex vivo
0.00
Animal model
Mouse model: eight-week-old male C57BL/6J mice
1.00
Diet/model
Unilateral blast-induced hearing loss model: controlled unilateral double blasts (~22 psi exposure pressure) to the left ear, 30 min apart, using a custom-built compressed air-driven system.
1.00
Клиника (11 полей)
Drug
7,8-dihydroxyflavone
1.00
Indication
blast-induced hearing loss
0.90
Patient subgroups
0.00
Safety concerns
0.00
Off-target
0.00
Trial stage
preclinical
0.90
Pharma competitors
0.00
AE severity
0.00
MOA weight loss
0.00
Endpoints
improvement in hearing recovery; significant reductions in ABR thresholds in ipsilateral ear at 4 weeks post-blast
0.90
Approved
False
0.90