Search

Objective: This study analyzed the associations between measured levels of aquaporin (AQP) mRNAs and clinical manifestations in patients with various types of otitis media (OM)., Methods: AQP1, 2, 3, 4, 5, 6, 8, and 10 mRNA levels were assayed by real-time PCR from 57 patients with chronic otitis media (COM), 24 patients with cholesteatomatous otitis media (choleOM), and 82 patients with otitis media with effusion (OME). The relationships of these mRNA levels with the presence of bacteria, the type of hearing loss, and clinical manifestations of OM types were evaluated., Results: All eight AQP mRNAs were expressed in inflammatory tissue, chole matrix, and effusion fluid obtained from all 163 patients with OM. The levels in OME of AQP2, 4, 6, and 10 mRNA; and the levels in choleOM of AQP1, 3, 4, and 10 mRNA were elevated significantly compared to the corresponding levels in COM (p < .05). The expression level of AQP8 mRNA did not differ among OM types. Among samples positive for bacterial culture, AQP1 mRNA was significantly higher in OME than in COM and choleOM, AQP5 mRNA was significantly lower in OME than in COM and choleOM, and AQP10 mRNA was significantly higher in OME and choleOM than in COM (p < .05)., Conclusions: The levels of expression of AQP mRNA are associated with the pathophysiology of OM.

Objective: The present study is aimed at determining the efficacy and exploring the mechanisms by which l-N-acetylcysteine (l-NAC) provides protection against tumor necrosis factor-alpha (TNFα)-induced oxidative stress damage and hair cell loss in 3-day-old rat organ of Corti (OC) explants. Previous work has demonstrated a high level of oxidative stress in TNFα-challenged OC explants. TNFα can potentially play a significant role in hair cell loss following an insult to the inner ear. l-NAC has shown to provide effective protection against noise-induced hearing loss in laboratory animals but mechanisms of this otoprotective effect are not well-defined., Design: Rat OC explants were exposed to either: (1) saline control (N = 12); (2) TNFα (2 μg/ml, N = 12); (3) TNFα+l-NAC (5 mM, N = 12); (4) TNFα+l-NAC (10 mM, N = 12); or (5) l-NAC (10 mM, N = 12). Outer hair cell (OHC) density, levels of reactive oxygen species (ROS), lipid peroxidation of cell membranes, gluthathione activity, and mitochondrial viability were assayed., Results: l-NAC (5 and 10 mM) provided protection for OHCs from ototoxic level of TNFα in OC explants. Groups treated with TNFα+l-NAC (5 mM) showed a highly significant reduction of both ROS (p < 0.01) and 4-hydroxy-2-nonenal immunostaining (p < 0.001) compared to TNFα-challenged explants. Total glutathione levels were low in TNFα-challenged explants compared to control and TNFα+l-NAC (5 mM) treated explants (p < 0.001)., Conclusions: l-NAC is a promising treatment for protecting auditory HCs from TNFα-induced oxidative stress and subsequent loss via programmed cell death.

Conclusion: Expression of connexin36 (Cx36) and electrical synapses formed by Cx36-containing gap junctions contribute to normal auditory brainstem response thresholds in mice., Objectives: Electrical synaptic transmission mediated by gap junctions has not been intensively studied in the auditory system. This study used transgenic mice with knockout of the gene coding for the major protein that forms neuronal gap junctions in mammalian brain (Cx36) to evaluate the role of Cx36 in murine hearing., Methods: Auditory brainstem response (ABR) thresholds and distortion product otoacoustic emissions (DPOAEs) were measured in 26 wild-type and 26 Cx36 knockout mice. ABR thresholds were used to assess auditory brainstem function at four frequencies. DPOAEs were delivered for seven frequency pairs to assess cochlear function., Results: The magnitudes of the 2f1-f2 distortion products were not different between Cx36 knockout and wild-type mice, suggesting similar cochlear function in the two groups. ABR thresholds were significantly elevated in the Cx36 knockout compared with the wild-type groups, suggesting impaired function in the auditory brainstem. The results suggest that electrical synapses formed by Cx36-containing gap junctions contribute to auditory sound processing and function at the level of the brainstem, not the cochlea. These findings may be important for understanding human auditory pathology.

Conclusion: Dynamic distribution of ototoxic gentamicin entry into inner hair cells (IHCs) may cause an interruption of cochlear ribbon synapse., Objective: To explore the pattern of uptake of gentamicin into IHCs, as well as its possible contribution to hearing loss., Methods: Adult C57 mice were injected intraperitoneally with gentamicin (100 mg/kg, conjugated with Texas Red ester) continuously for 14 days. The hearing thresholds were detected by auditory brainstem response (ABR) examinations. Immunostaining and confocal microscopy were utilized to trace gentamicin distribution, as well as the expression of RIBEYE/CtBP2 in mouse IHCs. Scanning electron microscopy (SEM) observation was used to find possible alterations of stereocilia., Results: The distribution of gentamicin in IHCs was first found on the 4th day and the accumulation of gentamicin was increased significantly on the 7th day after treatment, corresponding to the maximal elevation of the hearing threshold. However, the accumulation of gentamicin on the 14th day did not show significant differences compared with the level found on the 7th day. In addition, the uptake of gentamicin was excessively identified at or near the synaptic ribbons of IHCs throughout the 4th, 7th, and 14th days after the treatment, suggesting that cochlear ribbon synapses could be affected by ototoxic gentamicin exposure.

Conclusions: EGb761 treatment has a significant benefit with an early and preventive effect, reversing the deleterious effect of aging in the integrity of the rat cochlea, even in the late stage of the rat lifespan., Objectives: We previously reported a significant relationship between aging and apoptosis in the rat cochlea. This study was designed to investigate the effects of Ginkgo biloba leaf extract (EGb761) on age-associated cochlear caspase activation., Methods: Sprague-Dawley rats (n = 80) divided into two groups according to their age (4 months old, younger, YR, and 12 months old, aged-mature, AM) were treated with 100 mg/kg/day body weight of EGb761 extract dissolved in tap water for two periods: 4 and 12 months. Then cochleae were harvested to measure caspase activities, ATP levels, total superoxide dismutase (SOD) activity, and caspase-3 gene expression. Auditory steady-state responses (ASSR) threshold shifts were also measured before sacrifice of the rats., Results: EGb761 treatment prevents significantly aging-related caspase-induced activities within the cochleae in YR and AM rats. In the short EGb761 treatment, YR rats showed lower levels of caspase-3/7 than AM rats. In contrast, longer treatment did not show significant differences between YR and AM rats. Reduced caspase-3/7 activity in presence of EGb761 correlates with significant improvements of ASSR threshold shifts.

Conclusion: Styrene exposure causes hair cell death through both apoptotic and necrotic pathways and treatment with N-acetyl-L-cysteine (L-NAC) reduces styrene ototoxicity., Objective: Exposure to styrene causes hearing loss and hair cell death in the middle frequency region in the cochlea. The current study was designed to examine the cell death pathways and the protective effect of L-NAC against styrene-induced cochlear injuries., Materials and Methods: Seventeen rats were exposed to styrene by gavage at 400 mg/kg 5 days per week for 3 weeks. Nine of the styrene-treated rats received L-NAC by intraperitoneal injection (325 mg/kg), and the remaining eight rats received saline injections as controls. The styrene-induced hearing loss was assessed by auditory brainstem responses (ABRs). Apoptotic, necrotic, and missing hair cells were quantified using combined methods, including nuclear staining with propidium iodide, F-actin staining with FITC-phalloidin, and the TUNEL assay., Results: The styrene exposure caused a threshold shift of 15±4.3 dB. Both apoptosis and necrosis were involved in the pathogenesis of the cochlear lesion, but apoptosis appeared to be the major cell death pathway leading to the styrene ototoxicity. Treatment with L-NAC reduced the number of missing and dying outer hair cells (OHCs) and reduced the styrene-induced hearing loss.