The mechanoelectrical transducer channel is not required for regulation of cochlear blood flow during loud sound exposure in mice

Abstract

The mammalian cochlea possesses unique acoustic sensitivity due to a mechanoelectrical 'amplifier', which requires the metabolic support of the cochlear lateral wall. Loud sound exposure sufficient to induce permanent hearing damage causes cochlear blood flow reduction, which may contribute to hearing loss. However, sensory epithelium involvement in the cochlear blood flow regulation pathway is not fully described. We hypothesize that genetic manipulation of the mechanoelectrical transducer complex will abolish sound induced cochlear blood flow regulation. We used salsa mice, a Chd23 mutant with no mechanoelectrical transduction, and deafness before p56. Using optical coherence tomography angiography, we measured the cochlear blood flow of salsa and wild-type mice in response to loud sound (120 dB SPL, 30 minutes low-pass filtered noise). An expected sound induced decrease in cochlear blood flow occurred in CBA/CaJ mice, but surprisingly the same sound protocol induced cochlear blood flow increases in salsa mice. Blood flow did not change in the contralateral ear. Disruption of the sympathetic nervous system partially abolished the observed wild-type blood flow decrease but not the salsa increase. therefore sympathetic activation contributes to sound induced reduction of cochlear blood flow. Additionally a local, non-sensory pathway, potentially therapeutically targetable, must exist for cochlear blood flow regulation.

Norepinephrine protects against cochlear outer hair cell damage and noise-induced hearing loss via α2A-adrenergic receptor

“…After noise exposure, dexmedetomidine displayed protective effects against NIHL [ 47 ]. In mice, manipulation of adrenergic inputs to the cochlea confirmed that SNS regulates cochlear blood flow in response to intense loud sound exposure [ 48 ]. However, these findings are contradictory.…”

Three-dimensional mouse cochlea imaging based on the modified Sca/eS using confocal microscopy

“…Recently, in vivo live cochlear imaging using two-photon microscopy revealed that the gentamicin transporter, expressed in the SV and involved in the blood−labyrinthine−barrier function, protects against gentamicin-induced hearing loss, which causes drug-induced hearing loss in a significant patient population (Kim and Ricci 2022 ). Including drug-induced hearing loss, SV is an important component because sound exposure, which causes noise-induced hearing loss, decreases SV blood flow (Burwood et al 2020 ). Previous reports have revealed cochlear blood vessel details.…”

Sympathetic Nervous System Regulation of Auditory Function

“…By regulating arteriole diameter, the vessel-associated component has a significant effect on CBF [Brechtelsbauer et al, 1990;Laurikainen et al, 1993Laurikainen et al, , 1997Ren et al, 1993b]. Disruption of the sympathetic nervous system partially abolished, found that sympathetic activation contributes to sound-induced reduction of CBF [Burwood et al, 2020]. Unilateral and bilateral SG blockade resulted in effects of differing magnitude on CBF on each side, although both resulted in an increase in CBF.…”