Preservation Of Auditory Function Research Articles

Cochlear glial cells mediate glutamate uptake through a sodium-independent transporter

Since glutamate is the primary excitatory neurotransmitter in the mammalian cochlea, the mechanisms for the removal of glutamate from the synaptic and extrasynaptic spaces are critical for maintaining normal function of this region. Glial cells of inner ear are crucial for regulation of synaptic transmission throughout since it closely interacts with neurons along the entire auditory pathway, however little is known about the activity and expression of glutamate transporters in the cochlea. In this study, using primary cochlear glial cells cultures obtained from newborn Balb/C mice, we determined the activity of a sodium-dependent and sodium-independent glutamate uptake mechanisms by means of High Performance Liquid Chromatography. The sodium-independent glutamate transport has a prominent contribution in cochlear glial cells which is similar to what has been demonstrated in other sensory organs, but it is not found in tissues less susceptible to continuous glutamate-mediated injuries. Our results showed that xCG− system is expressed in CGCs and is the main responsible for sodium-independent glutamate uptake. The identification and characterization of the xCG− transporter in the cochlea suggests a possible role of this transporter in the control of extracellular glutamate concentrations and regulation of redox state, that may aid in the preservation of auditory function.

Underwater Endoscopic Ear Surgery for Closure of Cholesteatomatous Labyrinthine Fistula With Preservation of Auditory Function.

To analyze the outcomes of the underwater endoscopic ear surgery (UWEES) technique for closure of cholesteatomatous labyrinthine fistula (LF) with preservation of auditory function. Retrospective case review study. Tertiary referral center. A total of 12 patients with cholesteatomatous LF. Surgical method of closure using UWEES for cholesteatomatous LF to minimize inner ear damage. Artificial cerebrospinal fluid (CSF) was used as the perfusate, except for earlier cases when saline was employed. Comparison of bone conductance hearing level (BCHL) before and after surgery. A change of BCHL less than 10 dB was defined as successful preservation of bone conductance hearing. All cases of LF were treated successfully by closure using the UWEES technique. Seven cases were type I, one was type IIa, and four were type III according to the Milewski and Dornhoffer classification of LF. The average LF size was 3.1 mm (1-7 mm). Eleven patients were evaluated and their bone conductance hearing was well preserved in all of them (11/11). One patient was too young for preoperative evaluation of BCHL, but hearing preservation was verified 2 years later at the age of 6 years. Remarkably, none of the patients complained of vertigo, except for only a slight manifestation on postoperative day 1. The UWEES technique was effective for closure of cholesteatomatous LF with preservation of auditory function.

Quantitative PCR analysis and protein distribution of drug transporter genes in the rat cochlea

Membrane transporters can be major determinants in the targeting and effectiveness of pharmaceutical agents. A large number of biologically important membrane transporters have been identified and localized to a variety of tissues, organs and cell types. However, little is known about the expression of key membrane transporters in the inner ear, a promising site for targeted therapeutics, as well as a region vulnerable to adverse drug reactions and environmental factors. In this study, we examined the levels of endogenous membrane transporters in rat cochlea by targeted PCR array analysis of 84 transporter genes, followed by validation and localization in tissues by immunohistochemistry. Our studies indicate that several members of the SLC, VDAC and ABC membrane transporter families show high levels of expression, both at the RNA and protein levels in the rat cochlea. Identification and characterization of these membrane transporters in the inner ear have clinical implications for both therapeutic and cytotoxic mechanisms that may aid in the preservation of auditory function.

Effects of a dexamethasone-releasing implant on cochleae: A functional, morphological and pharmacokinetic study

AimThis study evaluated the impact of a dexamethasone-releasing silicone implant on hearing function preservation, cochlear morphology and perilymph pharmacokinetics after cochlear implantation. MethodsGuinea pigs were implanted unilaterally with silicone rods containing either 2% dexamethasone (DEXA group, n = 18) or no dexamethasone (control group, n = 17). Auditory brainstem response (ABR) and distortion product otoacoustic emissions (DPOAEs) were measured preoperatively and over 6 months postoperatively. Cochlear histology using standard hematoxylin and eosin (H&E) staining and tumor necrosis factor (TNF)-alpha staining was performed 1 month postoperatively. Twenty-two guinea pigs were involved in the pharmacokinetic study, and real-time drug concentrations in perilymph were investigated using high-performance liquid chromatography (HPLC). The Mann–Whitney U test (1-tailed) was used for statistical analyses. ResultsABR and DPOAE testing demonstrated decreased hearing function immediately postoperatively followed by a progressive hearing loss within the first day postoperatively. There was almost no observable hearing improvement in the control group from 1 week to 6 months postoperatively, but hearing levels in the DEXA group improved gradually from 1 week to 12 weeks. Hearing loss in the DEXA and control group was 5.0 ± 3.4 dB and 21.7 ± 5.3 dB, respectively at a 16-kHz stimulus frequency 6 months postoperatively. The difference in threshold shifts was present throughout all measured frequencies, and it was significant at 4–24 kHz. The morphological study revealed new fibrosis formation in the scala tympani, which encapsulated the implanted electrode. TNF-alpha positive staining in the cochleae of the DEXA group was less evident than the control group. The pharmacokinetic study revealed a peak perilymph concentration 30 min postoperatively and sustained dexamethasone release at least 1 week postoperatively. ConclusionCochlear implants that incorporate dexamethasone can release drug chronically in the inner ear and induce significant long-term recovery and preservation of auditory function after implantation.

Cyclic Alternating Pattern in congenital deaf – quantitative and topographic analysis

Introduction Sleep is a reversible behavioral state with attenuation of sensorial modalities and relative preservation of auditory function. Cyclic Alternating Pattern (CAP) is related to sleep instability and arousal. It is formed by CAP (phases A (A1, A2, A3) + B) and NCAP cycles. A1 subtype indicates maintenance of NREM sleep neuronal mechanisms; A2 and A3 are related to sleep instability and onset REM mechanisms. Congenital deaf sleep is a good model of sustained auditory deprivation and an important tool in the study of noise effect in sleep. In this study we aim to 1. Evaluate if the absence of acoustic perturbation in deaf promotes sleep stability; and 2. Evaluate the effect of provoked arousals in congenital deaf and normal-hearing subjects sleep. Materials and methods Eight congenital deaf and eight normal-hearing volunteers were matched according to age and gender. Video-polisonography were made on two consecutive nights, in lab environment, and provoked arousals after every 5 min of stable REM were performed. CAP Rate, Duration, Time Distribution and Topographic Mapping of the frequency bands 0.2–2.5 Hz (FB 1) and 7–12 Hz (FB2) were measured to accomplish aim 1; for aim 2 CAP density (no. events/ sleep time) were obtained for the periods before (PB) and after provoked arousals (AA – 30 min period after the arousal). SPSS 16.0 was used for statistical analysis purposes using p Results Contrary to the expectations, the sleep of the congenital deaf is more unstable as it presents increased A3 rate (p = 0.017) and time variations (p = 0.045) as well as evidence of decreased A1 rate and duration. The deaf subjects have compromised CAP rhythmicity: CAP cycle (p = 0,133) and A1 subtype (p = 0,138) do not vary along the night and there is no clear repetitive and cyclical A2 and A3 pattern in association with REM-on mechanisms. These subjects presented higher spectral power in parieto-occipital regions for A1 (p = 0.049 – BF1) and temporal posterior for A2 (p = 0.015 – FB 1) and B (p = 0.049 – FB 1 e p = 0.033 – FB 2) possibly as a result of cerebral modifications due to deafness. Deaf subjects seem more sensitive to provoked sleep interruption with remarkable decrease of A1 (p = 0/015) in AA periods. Conclusion Deaf subjects have more unstable sleep and higher sensitivity to provoked sleep interruption; compromised CAP rhythmicity as well as cortical and spectral modifications in posterior regions, possibly related to their clinical condition. Acknowledgements Funded by: Fundacao BIAL (No. 107/02 ). Work supported by Helder Bertolo, Joana Pires and Rosa Santos.

Cerebellar Ataxia With Neuropathy and Bilateral Vestibular Areflexia Syndrome

Szmulewicz, David J.*; Merchant, Saumil N.†; Halmagyi, Gabor Michael‡ Author Information

Behavioral investigation of some possible effects of the central olivocochlear pathways in transgenic mice

This study investigated the auditory behaviors of transgenic mice with deletions of α9 nicotinic acetylcholine receptor subunits. In the normal mammalian cochlea, the mechanical properties of outer hair cells are modified by the release of acetylcholine from olivocochlear efferent terminals. Electrophysiological correlates of this efferent feedback have not been demonstrated in α9 knockout mice, presumably because they are mediated by α9 receptors. Previous studies have associated lesions of olivocochlear pathways with hearing impairments in background noise. The prediction that α9 knockout mice would show similar deficits was tested by collecting psychophysical thresholds for tone detection and intensity discrimination from knockout mice, within-strain control subjects, and CBA/CaJ mice. Comparable performance was observed for the subject groups in quiet and in continuous background noise. The preservation of auditory function in α9 knockout mice suggests that central efferent pathways work in combination with the peripheral olivocochlear system to enhance hearing in noise, and may compensate for profound manipulations of peripheral feedback in highly routine testing procedures. An intriguing possibility is that these central mechanisms include the brainstem collaterals of olivocochlear neurons since their post-synaptic targets do not express α9 receptors and therefore are likely to maintain their effects in α9 knockout mice.

Early Diagnosis of Acoustic Neuroma (1989) After Experience of 37 Cases

Although the diagnosis of acoustic neuroma as classically described is generally thought to be easy, this is not always true for this so-called "ear tumor" which is localized within the internal auditory meatus. Recently, remarkable progress has been made in the diagnostic instrumentation and operative techniques used to treat acoustic neuroma, emphasizing the need for early diagnosis so that treatment can take place earlier than before. Through early diagnosis, some cases of total resection of acoustic neuroma have recently become possible, with preservation of not only facial nerve function, but preservation of auditory function as well. In the present report, we outline the early diagnosis of acoustic neuroma by summarizing 37 cases of acoustic neuroma experienced at our institution. We discuss historical presentations, and laboratory tests used in diagnosis including pure tone audiometry, speech audiometry, auditory brainstem evoked response (ABR), vestibular caloric stimulation, and computed tomography (CT) enhanced by introduction of air into the posterior fossa. Two representative cases are also presented. It should be emphasized that no clinical test is 100% sensitive or specific, and attention must be paid to chronological discrepancies in the patient's presentation and "cookbook"-type approaches to evaluation should be avoided.