Silicone-based AC102-loaded cochlear implant coatings protect residual hearing in an animal model of cochlear implantation.

Cochlear implant users with residual hearing benefit synergistically from combined electrical stimulation via the cochlear implant and preserved residual hearing after surgery. However, direct mechanical trauma and subsequent inflammation may deteriorate hearing function. AC102, a novel otoprotective pyridoindole with anti-apoptotic and anti-oxidative properties significantly improved hearing recovery following cochlear implantation when administered intratympanically prior to surgery.

A preoperative dose of the pyridoindole AC102 improves the recovery of residual hearing in a gerbil animal model of cochlear implantation.

Sensorineural hearing loss (SNHL) is the most common sensory deficit worldwide. Due to the heterogeneity of causes for SNHL, effective treatment options remain scarce, creating an unmet need for novel drugs in the field of otology. Cochlear implantation (CI) currently is the only established method to restore hearing function in profound SNHL and deaf patients.

From the outer ear to the nerve: A complete computer model of the peripheral auditory system.

Computer models of the individual components of the peripheral auditory system - the outer, middle, and inner ears and the auditory nerve - have been developed in the past, with varying level of detail, breadth, and faithfulness of the underlying parameters. Building on previous work, we advance the modeling of the ear by presenting a complete, physiologically justified, bottom-up computer model based on up-to-date experimental data that integrates all of these parts together seamlessly. The detailed bottom-up design of the present model allows for the investigation of partial hearing mechanisms and their defects, including genetic, molecular, and microscopic factors.

Computational Evaluation of Cochlear Implant Surgery Outcomes Accounting for Uncertainty and Parameter Variability.

Cochlear implantation (CI) is a complex surgical procedure that restores hearing in patients with severe deafness. The successful outcome of the implanted device relies on a group of factors, some of them unpredictable or difficult to control. Uncertainties on the electrode array position and the electrical properties of the bone make it difficult to accurately compute the current propagation delivered by the implant and the resulting neural activation.

Challenging aspects of contemporary cochlear implant electrode array design.

Objective: A design comparison of current perimodiolar and lateral wall electrode arrays of the cochlear implant (CI) is provided. The focus is on functional features such as acoustic frequency coverage and tonotopic mapping, battery consumption and dynamic range. A traumacity of their insertion is also evaluated.

A multiscale imaging and modelling dataset of the human inner ear.

Understanding the human inner ear anatomy and its internal structures is paramount to advance hearing implant technology. While the emergence of imaging devices allowed researchers to improve understanding of intracochlear structures, the difficulties to collect appropriate data has resulted in studies conducted with few samples. To assist the cochlear research community, a large collection of human temporal bone images is being made available.

Towards a Complete In Silico Assessment of the Outcome of Cochlear Implantation Surgery.

Cochlear implantation (CI) surgery is a very successful technique, performed on more than 300,000 people worldwide. However, since the challenge resides in obtaining an accurate surgical planning, computational models are considered to provide such accurate tools. They allow us to plan and simulate beforehand surgical procedures in order to maximally optimize surgery outcomes, and consequently provide valuable information to guide pre-operative decisions.

NANOCI-Nanotechnology Based Cochlear Implant With Gapless Interface to Auditory Neurons.

: Cochlear implants (CI) restore functional hearing in the majority of deaf patients. Despite the tremendous success of these devices, some limitations remain. The bottleneck for optimal electrical stimulation with CI is caused by the anatomical gap between the electrode array and the auditory neurons in the inner ear.

Automatic Model Generation Framework for Computational Simulation of Cochlear Implantation.

Recent developments in computational modeling of cochlear implantation are promising to study in silico the performance of the implant before surgery. However, creating a complete computational model of the patient's anatomy while including an external device geometry remains challenging. To address such a challenge, we propose an automatic framework for the generation of patient-specific meshes for finite element modeling of the implanted cochlea.

Patient-specific simulation of implant placement and function for cochlear implantation surgery planning.

We present a framework for patient specific electrical stimulation of the cochlea, that allows to perform in-silico analysis of implant placement and function before surgery. A Statistical Shape Model (SSM) is created from high-resolution human μCT data to capture important anatomical details. A Finite Element Model (FEM) is built and adapted to the patient using the results of the SSM.

Functional simulation of the cochlea for implant optimization.

Cochlear implantation is a surgical technique which aims to restore hearing in people with deep hearing loss. However, outcomes of the surgery still exhibit a large variability between patients. Among the factors that contribute to variability the most important are morphological differences in anatomical structures between patients and incorrect implant placements.

Reduced electromotility of outer hair cells associated with connexin-related forms of deafness: an in silico study of a cochlear network mechanism.

Mutations in the GJB2 gene encoding for the connexin 26 (Cx26) protein are the most common source of nonsyndromic forms of deafness. Cx26 is a building block of gap junctions (GJs) which establish electrical connectivity in distinct cochlear compartments by allowing intercellular ionic (and metabolic) exchange. Animal models of the Cx26 deficiency in the organ of Corti seem to suggest that the hearing loss and the degeneration of outer hair cells (OHCs) and inner hair cells is due to failed K(+) and metabolite homeostasis.

The role of potassium recirculation in cochlear amplification.

Purpose Of Review: Normal cochlear function depends on maintaining the correct ionic environment for the sensory hair cells. Here we review recent literature on the cellular distribution of potassium transport-related molecules in the cochlea.

Recent Findings: Transgenic animal models have identified novel molecules essential for normal hearing and support the idea that potassium is recycled in the cochlea.

Three-dimensional current flow in a large-scale model of the cochlea and the mechanism of amplification of sound.

The mammalian inner ear uses its sensory hair cells to detect and amplify incoming sound. It is unclear whether cochlear amplification arises uniquely from a voltage-dependent mechanism (electromotility) associated with outer hair cells (OHCs) or whether other mechanisms are necessary, for the voltage response of OHCs is apparently attenuated excessively by the membrane electrical filter. The cochlea contains many thousands of hair cells organized in extensive arrays, embedded in an electrically coupled system of supporting cells.

The enhancement of HCN channel instantaneous current facilitated by slow deactivation is regulated by intracellular chloride concentration.

The hyperpolarization-activated cation current I (f) plays a key role in the modulation of rhythmic activity in cardiac pacemaker cells and spontaneously firing neurons. I (f) is generated by hyperpolarization-activated cyclic nucleotide-gated channels (HCN1-HCN4) and comprises two components: the fast instantaneous current (I (INS)) and the slowly developing steady-state current (I (SS)). We found that in I (f) traces evoked by consecutive hyperpolarization, the I (INS) amplitude of the second trace was up to 50% larger than the first.

A novel mechanism of modulation of hyperpolarization-activated cyclic nucleotide-gated channels by Src kinase.

Hyperpolarization-activated cyclic nucleotide-gated channels (HCN1-4) play a crucial role in the regulation of cell excitability. Importantly, they contribute to spontaneous rhythmic activity in brain and heart. HCN channels are principally activated by membrane hyperpolarization and binding of cAMP.

The murine HCN3 gene encodes a hyperpolarization-activated cation channel with slow kinetics and unique response to cyclic nucleotides.

Hyperpolarization-activated cation channels of the HCN gene family are crucial for the regulation of cell excitability. Importantly, these channels play a pivotal role in the control of cardiac and neuronal pacemaker activity. Dysfunction of HCN channels has been associated with human diseases, including cardiac arrhythmia, epilepsy, and neuropathic pain.

Histidine 518 in the S6-CNBD linker controls pH dependence and gating of HCN channel from sea-urchin sperm.

Sperm motility is a tightly regulated process. One of the crucial factors determining the swimming of the sea-urchin sperm is an elevation of intracellular pH (pH(i)). The possibility that its hyperpolarisation-activated cyclic nucleotide-gated channel (SpHCN) is modulated directly by pH is addressed here.

Pore topology of the hyperpolarization-activated cyclic nucleotide-gated channel from sea urchin sperm.

The current flow through hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, referred to as I(h), plays a major role in several fundamental biological processes. The sequence of the presumed pore region of HCN channels is reminiscent of that of most known K(+)-selective channels. In the present work, the pore topology of an HCN channel from sea urchin sperm, called SpHCN, was investigated by means of the substituted-cysteine accessibility method (SCAM).