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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
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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
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0.00
Экспрессия (8 полей)
Tissue expression
—
0.00
In vitro
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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