C-Phycocyanin Attenuates Noise-Induced Cochlear Synaptopathy via the Inhibition of Oxidative Stress and Intercellular Adhesion Molecule-1 in the Cochlea.

The synapses between inner hair cells (IHCs) and spiral ganglion neurons (SGNs) are the most vulnerable structures in the noise-exposed cochlea. Cochlear synaptopathy results from the disruption of these synapses following noise exposure and is considered the main cause of poor speech understanding in noisy environments, even when audiogram results are normal. Cochlear synaptopathy leads to the degeneration of SGNs if damaged IHC-SGN synapses are not promptly recovered. Oxidative stress plays a central role in the pathogenesis of cochlear synaptopathy. C-Phycocyanin (C-PC) has antioxidant and anti-inflammatory activities and is widely utilized in the food and drug industry. However, the effect of the C-PC on noise-induced cochlear damage is unknown. We first investigated the therapeutic effect of C-PC on noise-induced cochlear synaptopathy. In vitro experiments revealed that C-PC reduced the H2O2-induced generation of reactive oxygen species in HEI-OC1 auditory cells. H2O2-induced cytotoxicity in HEI-OC1 cells was reduced with C-PC treatment. After white noise exposure for 3 h at a sound pressure of 118 dB, the guinea pigs intratympanically administered 5 µg/mL C-PC exhibited greater wave I amplitudes in the auditory brainstem response, more IHC synaptic ribbons and more IHC-SGN synapses according to microscopic analysis than the saline-treated guinea pigs. Furthermore, the group treated with C-PC had less intense 4-hydroxynonenal and intercellular adhesion molecule-1 staining in the cochlea compared with the saline group. Our results suggest that C-PC improves cochlear synaptopathy by inhibiting noise-induced oxidative stress and the inflammatory response in the cochlea.

Quantitative Assessment of Cochlear Histopathologic Findings in Patients With Suppurative Labyrinthitis.

IMPORTANCE: Better understanding of the effects of suppurative labyrinthitis (SL) on cochlear elements will aid the development of new approaches to treat its sequelae and complications in the ear. OBJECTIVE: To quantitatively evaluate the effects of SL on cochlear elements in humans. DESIGN, SETTING, AND PARTICIPANTS: A comparative study was conducted at a tertiary academic medical center from October 20, 2014, to January 3, 2015, of the histopathologic characteristics of 28 archived human temporal bone samples from 19 deceased patients with SL and 20 temporal bone samples from 14 deceased, age-matched controls. EXPOSURES: Evaluation of archived human temporal bone samples. MAIN OUTCOMES AND MEASURES: The locations of SL in the inner ear and the degree of endolymphatic hydrops were noted; the area of the stria vascularis and the spiral ligament in all turns of the cochlea at the midmodiolar level and in the adjacent 2 sections were measured; and the number of remaining outer and inner hair cells of the cochlea were counted to calculate the loss of both types of cells. To evaluate the loss of fibrocytes in the spiral ligament, a rating scale in each cochlear turn was used. For each segment of the cochlea, the number of spiral ganglion cells was determined. Outcomes between the group with SL and the control group were compared. RESULTS: Of the 28 temporal bone samples from the 19 deceased patients (16 men and 3 women; mean [SD] age, 23.1 [24.6] years) with SL, all showed SL in the scala tympani of the basal turn. In the group with SL vs the control group, the mean (SD) loss of outer hair cells was significantly higher in the lower (28.6% [11.4%] vs 12.4% [6.2%]; P = .02) and upper (22.3% [9.7%] vs 8.8% [3.2%]; P = .01) basal cochlear turn, the mean (SD) loss of inner hair cells was significantly higher in the lower (15.4% [6.7%] vs 2.6% [1.1%]; P = .02) and upper (10.6% [4.6%] vs 2.2% [0.7%]; P = .03) basal cochlear turn, the mean (SD) total number of spiral ganglion cells (28,132 [2068] vs 30,358 [2036]; P = .001) and the mean (SD) number of spiral ganglion cells in segment I (3554 [847] vs 4223 [649]; P = .003) was significantly decreased, the mean (SD) degree of atrophy of the stria vascularis in the lower (8455 [924] vs 9368 [1049] µm2; P = .003) and upper (7911 [837] vs 8474 [813] µm2; P = .02) basal cochlear turn was significantly greater, and the degree of endolymphatic hydrops was significantly greater (10 bone samples [36%] vs 1 [5%]; P = .006). No significant differences were found between the 2 groups in the number of fibrocytes and in the presence of atrophy of the spiral ligament in any cochlear turn. CONCLUSIONS AND RELEVANCE: This study demonstrates that SL can lead to cochlear damage, especially in the basal turn of the cochlea. These pathological observations have formed the basis for clinical findings of hearing loss and tinnitus detected in those patients with SL.

Behavioral assessment and identification of a molecular marker in a salicylate-induced tinnitus in rats.

Tinnitus is a non-observable phantom sensation. As such, it is a difficult condition to investigate and, to date, no effective treatment has been developed. To approach this phantom sensation, we aimed to develop a rat behavioral model of tinnitus using salicylate, an active component of aspirin known to induce tinnitus. We also aimed to establish a molecular marker of tinnitus by assessing the expression of transient receptor potential cation channel superfamily V-1 (TRPV1) in the rat auditory pathway during salicylate-induced tinnitus. Animals were trained to perform "an active avoidance task": animals were conditioned by electrical footshock to move to the other side of the conditioning box when hearing a sound. Animals received a single injection of saline or salicylate (400 mg/kg i.p.) and false positive responses were measured 2 h after injection as the number of movements during a silent period. The number of responses in salicylate-treated animals was highest when the conditioned stimulus was 60 dB sound pressure level (SPL) and 16 kHz. This indicates that animals could feel tinnitus 2 h after salicylate injection, equivalent to that induced by 60 dB SPL and 16 kHz. By means of real-time PCR and western blot analysis, TRPV1 expression was significantly upregulated in spiral ganglion cells 2 h after salicylate injection and this upregulation together with the increase in the number of false positive responses was significantly suppressed by capsazepine (10 mg/kg i.p.), a specific antagonist of TRPV1. This suggests that salicylate could induce tinnitus through activation of TRPV1 in the rat auditory pathway.