Time- and frequency-dependent changes in acoustic startle reflex amplitude following cyclodextrin-induced outer and inner cell loss

• Published in: Hearing research Vol. 415; p. 108441
• Main Authors: Zhang, Celia, Ding, Dalian, Sun, Wei, Hu, Bo Hua, Manohar, Senthilvelan, Salvi, Richard
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.03.2022
• Subjects: Acoustic startle reflex; Animals; Cochlea - pathology; Cyclodextrin; Cyclodextrins; Hair Cells, Auditory, Inner - pathology; Hair Cells, Auditory, Outer - pathology; Hearing loss; Ototoxicity; Presbycusis - pathology; Rats; Reflex, Startle; Cyclodextrin; Acoustic startle reflex; Ototoxicity; Hearing loss
• ISSN: 0378-5955; 1878-5891
• DOI: 10.1016/j.heares.2022.108441

•Acoustic startle reflex (ASR) amplitudes changed during cyclodextrin-induced hair cell loss.•Amplitudes typically declined in early phase of drug-induced outer hair cell (OHC) loss.•Amplitudes remained stable in the late-phase of drug-induced inner hair cell (IHC) loss.•Amplitudes were occasionally enhanced when the lesion was confined to cochlear base. The acoustic startle reflex (ASR) amplitude can be enhanced or suppressed by noise-induced hearing loss or age-related hearing loss; however, little is known about how the ASR changes when ototoxic drugs destroy outer hair cells (OHCs) and inner hair cells (IHCs). High doses of 2-hydroxypropyl-beta-cyclodextrin (HPβCD), a cholesterol-lowering drug used to treat Niemann-Pick Type disease type C1, initially destroy OHCs and then the IHCs 6–8 weeks later. Adult rats were treated with doses of HPβCD designed to produce a diversity of hair cell lesions and hearing losses. When HPβCD destroyed OHCs and IHCs in the extreme base of the cochlea and caused minimal high-frequency hearing loss, the ASR amplitudes were enhanced at 4-, 8- and 16 kHz. Enhanced ASR occurred during the first few weeks post-treatment when only OHCs were missing; little change in the ASR occurred 6–8-WK post-treatment. If HPβCD destroyed most OHCs and many IHCs in the basal half of the cochlea, high-frequency thresholds increased ∼50 dB, and ASR amplitudes were reduced ∼50% at 4-, 8- and 16-kHz. The ASR amplitude reduction occurred in the first few weeks post-treatment when the OHCs were degenerating. The ASR was largely abolished when most of the OHCs were missing over the basal two-thirds of the cochlea and a 40–50 dB hearing loss was present at most frequencies. These results indicate that high-doses of HPβCD generally lead to a decline in ASR amplitude as OHCs degenerate; however, ASR amplitudes were enhanced in a few cases when hair cell loss was confined to the extreme base of the cochlea.