Blood-labyrinth barrier disruption associates with hypercholesterolemia-induced hearing loss

Area of Science:

• Otorhinolaryngology
• Cardiovascular Science
• Neuroscience

Background:

• Hypercholesterolemia is a known risk factor for sensorineural hearing loss.
• The precise mechanisms linking high cholesterol to cochlear damage remain unclear.

Purpose of the Study:

• To investigate the mechanistic link between blood-labyrinth barrier (BLB) disruption and hypercholesterolemia-associated cochlear damage.
• To identify the BLB as a potential therapeutic target.

Main Methods:

• Utilized low-density lipoprotein receptor knockout (Ldlr-/-) mice fed a high-fat diet.
• Conducted auditory assessments including auditory brainstem response (ABR) and distortion product otoacoustic emissions (DPOAEs).
• Evaluated BLB integrity through vascular permeability, tight junction analysis, and cochlear histopathology.

Main Results:

• Hypercholesterolemic mice exhibited elevated ABR thresholds and reduced DPOAEs, indicating hearing loss.
• BLB disruption, characterized by increased permeability and damaged tight junctions, preceded hearing impairment.
• Cochlear histopathology revealed outer and inner hair cell loss.

Conclusions:

• Blood-labyrinth barrier disruption is a key mechanism in hypercholesterolemia-induced hearing loss.
• BLB integrity is compromised before the onset of detectable hearing deficits.
• Targeting the BLB offers a potential strategy for preventing hearing impairment associated with high cholesterol.