This narrative review describes experimental animal models of sensorineural hearing loss (SNHL) caused by ototoxic agents.Background: SNHL primarily results from damage to the sensory organ within the inner ear or the vestibulocochlear nerve (cranial nerve VIII). The main etiology of SNHL includes genetic diseases, presbycusis, ototoxic agents, infection, and noise exposure. Animal models with functional and anatomic damage to the sensory organ within the inner ear or the vestibulocochlear nerve mimicking the damage seen in humans are employed to explore the mechanism and potential treatment of SNHL. These animal models of SNHL are commonly established using ototoxic agents.Methods: A literature search of PubMed, Embase, and Web of Science was performed for research articles on hearing loss and ototoxic agents in animal models of hearing loss.Conclusions: Common ototoxic medications such as aminoglycoside antibiotics (AABs) and platinum antitumor drugs are extensively used to induce SNHL in experimental animals. The effect of ototoxic agents in vivo is influenced by the chemical mechanisms of the ototoxic agents, the species of animal, routes of administration of the ototoxic agents, and the dosage of ototoxic agents. Animal models of drug-induced SNHL contribute to understanding the hearing mechanism and reveal the function of different parts of the auditory system in humans.

Here, we developed a safe and highly effective nanocarrier using β-cyclodextrin (β-CD) and oligoarginine peptide (Arg8)-modified dendrimer-entrapped gold nanoparticles (Au@CD-PAMAM-Arg8), with a diameter of 5 nm, for improved delivery of dexamethasone (Dex) to the inner ear. The properties and in vivo distribution of the Au@CD-PAMAM-Arg8 were assessed in vitro, and a streptomycin (SM) ototoxicity model was used in vivo. Flow cytometry analysis of HEIOC1 cells treated with Au@CD-PAMAM-Arg8 and Au @CD-PAMAM at different time intervals indicated that cell uptake efficiency of the drug delivery carrier Au@CD-PAMAM-Arg8 was higher than that of Au @CD-PAMAM. Au@CD-PAMAM-Arg8 carrying Dex (Au@CD-PAMAM-Arg8/Dex) were mainly distributed in hair cells, the spiral ganglion, lateral wall, and nerve fibers and had stronger protective effects on the inner ear than Dex administration alone. In vivo tracer tests revealed that tympanic injection was significantly more effective than posterior ear injection, muscle injection, and tail vein injection, whereas clinical retro-auricular injection could not increase the efficiency of drug delivery into the ear. Electrocochleography results showed that Au@CD-PAMAM-Arg8/Dex significantly improved hearing in C57/BL6 mice after SM exposure. These findings indicate that Au@CD-PAMAM-Arg8 may be the useful drug carriers for the treatment of inner ear diseases.

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Introduction: Auditory brainstem response (ABR) is one of the commonly used methods in clinical settings to evaluate the hearing sensitivity and auditory function. The current ABR measurement usually adopts click sound as the stimuli. However, there may be partial ABR amplitude attenuation due to the delay characteristics of the cochlear traveling wave along the basilar membrane. To solve that problem, a swept-tone method was proposed, in which the show-up time of different frequency components was adjusted to compensate the delay characteristics of the cochlear basilar membrane; therefore, different ABR subcomponents of different frequencies were synchronized. Methods: The normal hearing group, moderate sensorineural hearing loss group, and severe sensorineural hearing loss group underwent click ABR and swept-tone ABR with different stimulus intensities. The latencies and amplitudes of waves I, III, and V in 2 detections were recorded. Results: It was found that the latency of each of the recorded I, III, and V waves detected by swept-tone ABR was shorter than that by click ABR in both the control group and experimental groups. In addition, the amplitude of each of the recorded I, III, and V waves, except V waves under 60 dB nHL in the moderate sensorineural hearing loss group, detected by swept-tone ABR was larger than that by click ABR. The results also showed that the swept-tone ABR could measure the visible V waves at lower stimulus levels in the severe sensorineural hearing loss group. Conclusion: Swept-tone improves the ABR waveforms and helps to obtain more accurate threshold to some extent. Therefore, the proposed swept-tone ABR may provide a new solution for better morphology of ABR waveform, which can help to make more accurate diagnosis about the hearing functionality in the clinic.

The inner ear is located deep in the temporal bone and has a complex anatomy. It is difficult to observe and obtain pathological tissues directly. Therefore, the diagnosis and treatment of inner ear diseases have always been a major clinical problem. The onset of inner ear disease can be accompanied by symptoms such as hearing loss, dizziness and tinnitus, which seriously affect people’s lives. Nanoparticles have the characteristics of small size, high bioavailability and strong plasticity. With the development of related research on nanoparticles in inner ear diseases, nanoparticles have gradually become a research hotspot in inner ear diseases. This review briefly summarizes the research progress, opportunities and challenges of the application of nanoparticles in inner ear diseases.