Dongzhen Yu

Addition of exogenous NAD+ prevents mefloquine-induced neuroaxonal and hair cell degeneration through reduction of caspase-3-mediated apoptosis in cochlear organotypic cultures.

Background Mefloquine is widely used for the treatment of malaria. However, this drug is known to induce neurological side effects including depression, anxiety, balance disorder, and sensorineural hearing loss. Yet, there is currently no treatment for these side effects. Principal Findings In this study, we show that the coenzyme NAD+, known to play a critical role in maintaining the appropriate cellular redox environment, protects cochlear axons and sensory hair cells from mefloquine-induced degeneration in cultured rat cochleae. Mefloquine alone destroyed hair cells and nerve fiber axons in rat cochlear organotypics cultures in a dose-dependent manner, while treatment with NAD+ protected axons and hair cells from mefloquine-induced degeneration. Furthermore, cochlear organs treated with mefloquine showed increased oxidative stress marker levels, including superoxide and protein carbonyl, and increased apoptosis marker levels, including TUNEL-positive nuclei and caspases-3. Treatment with NAD+ reduced the levels of these oxidative stress and apoptosis markers. Conclusions/Significance Taken together, our findings suggest that that mefloquine disrupts the cellular redox environment and induces oxidative stress in cochlear hair cells and nerve fibers leading to caspases-3-mediated apoptosis of these structures. Exogenous NAD+ suppresses mefloquine-induced oxidative stress and prevents the degeneration of cochlear axons and sensory hair cells caused by mefloquine treatment.

Local inhibition shapes duration tuning in the inferior colliculus of guinea pigs

Neural tuning to sound durations is a useful filter for the identification of a variety of sounds. Previous studies have shown that the interaction between excitatory and inhibitory inputs plays a role in duration selectivity in echolocating bats. However, this has not been investigated in non-echolocating mammals. In the inferior colliculus (IC) of these mammals, it is recognized that the excitatory responses to sounds are mediated through AMPA and NMDA receptors while the inhibitory input is mediated through gamma-aminobutyric acid (GABA) and glycine receptors. The present study explores the potential interplay between inhibitory and excitatory inputs and its role in the duration selectivity of IC neurons in guinea pigs. It was found that the application of bicuculline (BIC, a GABA A blocker) and/or strychnine (STRY, a glycine blocker) eliminated or reduced duration tuning in most units that were duration tuned (32 out of 39 for BIC, 50 out of 64 for STRY, respectively). The inhibitory input (either by GABA or by glycine) appeared to have a stronger regulating effect on the early excitation mediated by AMPA than on later excitation by NMDA. This is more distinguishable in neurons that show duration selectivity. In conclusion, the inhibitory effect on the early responses appears to be the main contributor for the duration selectivity of the IC in guinea pigs; potential mechanisms for this duration selectivity are also discussed.

Functional and structural changes in the chinchilla cochlea and vestibular system following round window application of carboplatin

Abstract Objective: In chinchillas, moderate doses of carboplatin administered systemically selectively destroy inner hair cells and type I vestibular hair cells; however, it is unclear whether this unique damage pattern persists if carboplatin is applied directly to the cochlea, how quickly the damage develops and what cell death pathways are involved. Study design: To address these questions, carboplatin (5 mg/ml, 50 µl) was applied to the round window. Results: Carboplatin caused a rapid decline in distortion product otoacoustic emissions, significantly increased compound action potential thresholds and caused massive inner hair cell loss and less severe outer hair cell loss. Hair cell loss was initially more severe in the base than the apex of the cochlea, but by 28 days post-treatment most cochlear hair cells were missing and hair cell density in the utricle, saccule and lateral crista was greatly reduced. At one day post-treatment, many hair cell nuclei were condensed or fragmented indicative of apoptosis, and expressed initiator caspase-8 and executioner caspase-3, but not initiator caspase-9. Carboplatin-treated animals circled towards the treated ear and during the swim test rolled towards the treated ear.Conclusion: These results indicate that local application of carboplatin causes loss of hair cells that begins near the base of the cochlea and spreads towards the apex with increasing survival time. Hair cell loss is initiated by caspase-8 followed by executioner caspase-3.

Comparative study of the efficacy of the canalith repositioning procedure versus the vertigo treatment and rehabilitation chair

Abstract Conclusion: Vertigo treatment and rehabilitation chair (TRV) may be suggested as the first choice for patients with posterior canal benign paroxysmal positional vertigo (p-BPPV). Objective: To investigate the short- and long-term treatment efficacy of the canalith repositioning procedure (CRP) versus TRV for patients with p-BPPV. Methods: A total of 165 patients with unilateral p-BPPV were assigned to either the CRP group or the TRV group. Patients were assessed at 1 week, 4 weeks, 3 months, and 6 months after their first treatment. The numbers of treatment sessions required for successful repositioning in both groups at 4 weeks, 3 months, and 6 months were recorded. Results: Treatment efficacy of patients in the TRV group was significantly better than that of patients in the CRP group 1 week after the first treatment. The number of treatment sessions needed for successful repositioning was significantly lower in the TRV group than in the CRP group at 4 weeks and 3 months after the first treatment.

Polybrene: Observations on cochlear hair cell necrosis and minimal lentiviral transduction of cochlear hair cells.

Polybrene is widely used to enhance viral transduction; however, little is known about the utility thereof, in enhancing lentiviral transduction of cochlear cells. In the present study, we examined the cytotoxic effects of polybrene, and the further effects thereof, on lentiviral transduction of cochlear cells, especially sensory hair cells. Cochlear basilar membranes of newborn rats were cultured and treated with 0.1-10 μg/mL polybrene for 24h to explore the potential development of ototoxicity. PI staining and TUNEL detection were used to evaluate necrosis or apoptosis of hair cell. Various doses of lentivirus-GFP were added to cochlear organotypic cultures with safe concentrations of polybrene, incubated for 24h, and cultured (in the absence of the virus and polybrene) for a further 48 h. Transduction efficiencies were evaluated. The results showed that polybrene at 0.1 μg/mL was safe to cochlear cells, and 0.5-10 μg/mL concentration induced hair cell necrosis in a dose-dependent manner. However, supporting cells were not damaged. Lentiviral vectors transduced into cochlear cells and 0.1 μg/mL polybrene enhanced transduction efficiency. However, hair cells were hardly transduced with lentiviral vectors either alone or in the presence of 0.1 μg/mL polybrene. The use of polybrene to aid lentiviral transduction of cochlear hair cells requires further attention.

Indications and Common Surgical Approaches for Cochlear Implantation in China

Cochlear implants have become widely used in the management of profound sensorineural hearing loss. With today’s technology and the demonstrated success of cochlear implantation, candidacy criteria have greatly widened. In this paper, we describe issues concerning the current indications and common surgical approaches to cochlear implantation in China.

Factor Analysis of Low-Frequency Repetitive Transcranial Magnetic Stimulation to the Temporoparietal Junction for Tinnitus

Objectives. We investigated factors that contribute to suppression of tinnitus after repetitive transcranial magnetic stimulation (rTMS). Methods. A total of 289 patients with tinnitus underwent active 1 Hz rTMS in the left temporoparietal region. A visual analog scale (VAS) was used to assess tinnitus loudness. All participants were interviewed regarding age, gender, tinnitus duration, laterality and pitch, audiometric parameters, sleep, and so forth. The resting motor thresholds (RMTs) were measured in all patients and 30 age- and gender-matched volunteers. Results. With respect to different factors that contribute to tinnitus suppression, we found improvement in the following domains: shorter duration, normal hearing (OR: 3.25, 95%CI: 2.01–5.27, p = 0.001), and without sleep disturbance (OR: 2.51, 95%CI: 1.56–4.1, p = 0.005) adjusted for age and gender. The patients with tinnitus lasting less than 1 year were more likely to show suppression of tinnitus (OR: 2.77, 95%CI: 1.48–5.19, p = 0.002) compared to those with tinnitus lasting more than 5 years. Tinnitus patients had significantly lower RMTs compared with healthy volunteers. Conclusion. Active low-frequency rTMS results in a significant reduction in the loudness of tinnitus. Significant tinnitus suppression was shown in subjects with shorter tinnitus duration, with normal hearing, and without sleep disturbance.

Effect of baclofen on neuronal activity in the medial vestibular nucleus after unilateral surgical labyrinthectomy in rats.

Conclusions: Ipsilateral and contralateral medial vestibular nuclei (MVN) neurons respond differently to systemic injection of baclofen (4-amino-3-(4-chlorophenyl)-butanoic acid), illustrating the plastic changes of the type B γ-aminobutyric acid (GABAB) receptor during vestibular compensation. Objectives: To investigate the responsiveness of MVN neurons to baclofen during the early, partially compensated period after unilateral surgical labyrinthectomy. Materials and methods: MVN were localized using field potentials evoked by electrical stimulation, along with a stereotaxic atlas of rat brain. Neuronal activity in MVN was recorded and analyzed in rats that had undergone labyrinthectomy with and without administration of baclofen. Results: After left labyrinthectomy the mean discharge rate in ipsilesional MVN decreased, but it was nearly restored by postoperative day 8. Baclofen (3 mg/kg) reversed the mean discharge rates between bilateral MVN at days 4 and 8 after surgical labyrinthectomy. In addition, the reduction ratio of the right MVN neurons was higher than that of the left MVN neurons.

Benign paroxysmal positional vertigo in children

To describe the clinical features of benign paroxysmal positional vertigo (BPPV) in children.

Video head impulse test results suggest that different pathomechanisms underlie sudden sensorineural hearing loss with vertigo and vestibular neuritis: Our experience in fifty-two patients

Sudden sensorineural hearing loss with vertigo and vestibular neuritis are two disorders that could be caused by similar pathomechanisms. A quick and convenient tool, the video head impulse test (vHIT), was developed to measure and quantitatively analyze the function of each semicircular canal. Auditory and vestibular function in the two disorders, using PTA and vHIT, could help determine whether these disorders have similar degree of severity and scope of affected semicircular canals. The affected semicircular canals and severity of functional loss in the canals differed between the SHLV and VN groups by assessing the vestibulo-ocular reflex(VOR) gain (vHIT-G) and asymmetry values. vHIT results were different in VN and SHLV groups, which may underlie different etiologies of VN and SHLV. This article is protected by copyright. All rights reserved.