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

Hypercholesterolemia is a recognized risk factor for sensorineural hearing loss. This study investigated the mechanistic link between blood-labyrinth barrier (BLB) disruption and hypercholesterolemia-associated cochlear damage. Low-density lipoprotein receptor knockout ( Ldlr −/− ) mice fed a high-fat diet for 8 weeks were used as the experimental model. Auditory assessments showed elevated auditory brainstem response (ABR) thresholds and distortion product otoacoustic emissions (DPOAEs), especially at high frequencies, consistent with hearing loss driven by outer hair cell dysfunction. BLB disruption occurred before hearing impairment, manifest as increased vascular permeability, damaged tight junctions and downregulated junctional protein levels. Cochlear histopathology confirmed outer and inner hair cell loss. These findings demonstrate a sequential and identify BLB as a key therapeutic target for preventing hypercholesterolemia-associated hearing impairment.