Detecting Cochlear Synaptopathy Through Curvature Quantification of the Auditory Brainstem Response
The sound-evoked electrical compound potential known as auditory brainstem response (ABR) represents the firing of a heterogenous population of auditory neurons in response to sound stimuli, and is often used for clinical diagnosis based on wave amplitude and latency. However, recent ABR applications to detect human cochlear synaptopathy have led to inconsistent results, mainly due to the high variability of ABR wave-1 amplitude. Here, rather than focusing on the amplitude of ABR wave 1, we evaluated the use of ABR wave curvature to detect cochlear synaptic loss. We first compared four curvature quantification methods using simulated ABR waves, and identified that the cubic spline method using five data points produced the most accurate quantification. We next evaluated this quantification method with ABR data from an established mouse model with cochlear synaptopathy. The data clearly demonstrated that curvature measurement is more sensitive and consistent in identifying cochlear synaptic loss in mice compared to the amplitude and latency measurements. We further tested this curvature method in a different mouse model presenting with otitis media. The change in curvature profile due to middle ear infection in otitis media is different from the profile of mice with cochlear synaptopathy. Thus, our study suggests that curvature quantification can be used to address the current ABR variability issue, and may lead to additional applications in the clinic diagnosis of hearing disorders.
Jianxin Bao
Segun Light Jegede
John W Hawks
Bethany Dade
Qiang Guan
Samantha Middaugh
Ziyu Qiu
Anna Levina
Tsung-Heng Tsai
Front Cell Neurosci
. 2022 Mar 9;16:851500. doi: 10.3389/fncel.2022.851500. eCollection 2022.
2022
English
Otoprotective Effects of Stephania tetrandra S. Moore Herb Isolate against Acoustic Trauma.
calcium channel; hair cells; noise-induced hearing loss; spiral ganglion neurons; Stephania tetrandra; synapse; Tetrandrine
Noise is the most common occupational and environmental hazard, and noise-induced hearing loss (NIHL) is the second most common form of sensorineural hearing deficit. Although therapeutics that target the free-radical pathway have shown promise, none of these compounds is currently approved against NIHL by the United States Food and Drug Administration. The present study has demonstrated that tetrandrine (TET), a traditional Chinese medicinal alkaloid and the main chemical isolate of the Stephania tetrandra S. Moore herb, significantly attenuated NIHL in CBA/CaJ mice. TET is known to exert antihypertensive and antiarrhythmic effects through the blocking of calcium channels. Whole-cell patch-clamp recording from adult spiral ganglion neurons showed that TET blocked the transient Ca(2+) current in a dose-dependent manner and the half-blocking concentration was 0.6 + 0.1 muM. Consistent with previous findings that modulations of calcium-based signaling pathways have both prophylactic and therapeutic effects against neural trauma, NIHL was significantly diminished by TET administration. Importantly, TET has a long-lasting protective effect after noise exposure (48 weeks) in comparison to 2 weeks after noise exposure. The otoprotective effects of TET were achieved mainly by preventing outer hair cell damage and synapse loss between inner hair cells and spiral ganglion neurons. Thus, our data indicate that TET has great potential in the prevention and treatment of NIHL.
Yu Yan; Hu Bing; Bao Jianxin; Mulvany Jessica; Bielefeld Eric; Harrison Ryan T; Neton Sarah A; Thirumala Partha; Chen Yingying; Lei Debin; Qiu Ziyu; Zheng Qingyin; Ren Jihao; Perez-Flores Maria Cristina; Yamoah Ebenezer N; Salehi Pezhman
Journal of the Association for Research in Otolaryngology : JARO
2018
2018-12
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<a href="http://doi.org/10.1007/s10162-018-00690-3" target="_blank" rel="noreferrer noopener">10.1007/s10162-018-00690-3</a>