N-acetylcysteine microparticles reduce cisplatin-induced RSC96 Schwann cell toxicity.

Objectives: Cisplatin is known to cause inner ear dysfunction. There is growing evidence that cisplatin-induced demyelination of spiral or Scarpa's ganglion neurons may play an additional role in drug-induced ototoxicity alongside afferent neuron injury. As Schwann cells produce myelin, there may be an opportunity to reduce ototoxic inner ear damage by promoting Schwann cell viability.

An in vitro model for postoperative cranial nerve dysfunction and a proposed method of rehabilitation with N-acetylcysteine microparticles.

Purpose: When operating near cranial motor nerves, transient postoperative weakness of target muscles lasting weeks to months is often observed. As nerves are typically intact at a procedure's completion, paresis is hypothesized to result from a combination of neurapraxia and axonotmesis. As both neurapraxia and axonotmesis involve Schwann cell injury and require remyelination, we developed an in vitro RSC96 Schwann cell model of injury using hydrogen peroxide (HO) to induce oxidative stress and investigated the efficacy of candidate therapeutic agents to promote RSC96 viability.

N-acetylcysteine Microparticles Reduce Cisplatin-induced RSC96 Schwann Cell Toxicity.

Objectives: Cisplatin is known to cause inner ear dysfunction. There is growing evidence that cisplatin-induced demyelination of spiral or Scarpa's ganglion neurons may play an additional role in drug-induced ototoxicity alongside afferent neuron injury. As Schwann cells produce myelin, there may be an opportunity to reduce ototoxic inner ear damage by promoting Schwann cell viability.

Designing a Prolonged Method of Therapeutic Delivery to Support Rehabilitation From Ototoxic Damage in a Schwann Cell Model.

Hypothesis: The ototoxicity of gentamicin and cisplatin can be evaluated with a Schwann cell model to screen for otoprotective agents that can be encapsulated into poly (lactic-co-glycolic acid) (PLGA) microparticles for drug delivery to the inner ear.

Background: Aminoglycosides and cisplatin are widely prescribed but known to cause ototoxicity. There is strong evidence that compromise to Schwann cells ensheathing inner ear afferent neurons results in inner ear dysfunction mimicking drug-induced ototoxicity.

Inflight head stabilization associated with wingbeat cycle and sonar emissions in the lingual echolocating Egyptian fruit bat, Rousettus aegyptiacus.

Sensory processing of environmental stimuli is challenged by head movements that perturb sensorimotor coordinate frames directing behaviors. In the case of visually guided behaviors, visual gaze stabilization results from the integrated activity of the vestibuloocular reflex and motor efference copy originating within circuits driving locomotor behavior. In the present investigation, it was hypothesized that head stabilization is broadly implemented in echolocating bats during sustained flight, and is temporally associated with emitted sonar signals which would optimize acoustic gaze.

Translations of Steinhausen's Publications Provide Insight Into Their Contributions to Peripheral Vestibular Neuroscience.

The quantitative relationship between angular head movement and semicircular canal function is most often referenced to the well-known torsion-pendulum model that predicts cupular displacement from input head acceleration. The foundation of this model can be traced back to Steinhausen's series of papers between 1927 and 1933 whereby he endeavored to document observations of cupular displacements that would directly infer movement of the endolymph resulting from angular rotation. He also was the first to establish the direct relationship between cupular displacement and compensatory eye movements.

Implantable Drug Reservoir Devices for Inner Ear Delivery of Pharmacotherapeutics.

Objective: Cisplatin is a platinum-based chemotherapeutic drug that secondarily induces toxicity in inner ear sensory epithelia, contributing to auditory and vestibular dysfunction. We describe the creation of a drug reservoir device (DRD) to combat this ototoxicity for the duration of chemotherapy. As ototoxic side effects of chemotherapy may limit an oncologist's ability to prescribe first-line agents such as cisplatin, mitigating such devastating effects through prolonged topical therapy would be tremendously valuable.

Calbindin expression in adult vestibular epithelia.

The mammalian vestibular epithelia exhibit a remarkably stereotyped organization featuring cellular characteristics under planar cell polarity (PCP) control. PCP mechanisms are responsible for the organization of hair cell morphologic polarization vectors, and are thought to be responsible for the postsynaptic expression of the calcium-binding protein calretinin that defines the utricular striola and cristae central zone. However, recent analyses revealed that subtle differences in the topographic expression of oncomodulin, another calcium-binding protein, reflects heterogeneous factors driving the subtle variations in expression.

Models of vestibular semicircular canal afferent neuron firing activity.

Semicircular canal afferent neurons transmit information about head rotation to the brain. Mathematical models of how they do this have coevolved with concepts of how brains perceive the world. A 19th-century "camera" metaphor, in which sensory neurons project an image of the world captured by sense organs into the brain, gave way to a 20th-century view of sensory nerves as communication channels providing inputs to dynamical control systems.

Oncomodulin Expression Reveals New Insights into the Cellular Organization of the Murine Utricle Striola.

Oncomodulin (OCM, aka β-parvalbumin) is an EF-hand calcium binding protein that is expressed in a restricted set of hair cells in the peristriolar region of the mammalian utricle. In the present study, we determined the topologic distribution of OCM among hair cell phenotypes to advance our understanding of the cellular organization of the striola and the relationship of these phenotypes with characteristics of tissue polarity. The distributions of OCM-positive (OCM+) hair cells were quantified in utricles of mature C57Bl/6 mice.

Partial Aminoglycoside Lesions in Vestibular Epithelia Reveal Broad Sensory Dysfunction Associated with Modest Hair Cell Loss and Afferent Calyx Retraction.

Although the effects of aminoglycoside antibiotics on hair cells have been investigated for decades, their influences on the dendrites of primary afferent neurons have not been widely studied. This is undoubtedly due to the difficulty in disassociating pathology to dendritic processes from that resulting from loss of the presynaptic hair cell. This was overcome in the present investigation through development of a preparation using that enabled direct perilymphatic infusion.

Spaceflight-induced synaptic modifications within hair cells of the mammalian utricle.

Exposure to the microgravity conditions of spaceflight alleviates the load normally imposed by the Earth's gravitational field on the inner ear utricular epithelia. Previous ultrastructural investigations have shown that spaceflight induces an increase in synapse density within hair cells of the rat utricle. However, the utricle exhibits broad physiological heterogeneity across different epithelial regions, and it is unknown whether capabilities for synaptic plasticity generalize to hair cells across its topography.

Distribution of high-conductance calcium-activated potassium channels in rat vestibular epithelia.

Voltage- and calcium-activated potassium channels (BK) are important regulators of neuronal excitability. BK channels seem to be crucial for frequency tuning in nonmammalian vestibular and auditory hair cells. However, there are a paucity of data concerning BK expression in mammalian vestibular hair cells.

Genome-wide screening for genetic loci associated with noise-induced hearing loss.

Noise-induced hearing loss (NIHL) is one of the more common sources of environmentally induced hearing loss in adults. In a mouse model, Castaneous (CAST/Ei) is an inbred strain that is resistant to NIHL, while the C57BL/6J strain is susceptible. We have used the genome-tagged mice (GTM) library of congenic strains, carrying defined segments of the CAST/Ei genome introgressed onto the C57BL/6J background, to search for loci modifying the noise-induced damage seen in the C57BL/6J strain.

Afferent synapses are present in utricular hair cells from otoconia-deficient mice.

The head tilt mouse (het/het, abbr. het) is a naturally occurring mutant whose salient phenotypic traits include the complete absence of otoconia in both the utricle and saccule. Cursory histologic evaluation has indicated that the neuroepithelia exhibit a normal appearance.

Dynamics and the single spike.

Responses of vestibular primary afferent neurons to head rotation exhibit fractional-order dynamics. As a consequence, the head tends to be in a localized region of its state-space at spike times of a particular neuron during arbitrary head movements, and single spikes can be interpreted as state measurements. We are developing a model of neural computations underlying trajectory prediction and control tasks, based on this experimental observation.

Fiber diameter distributions in the chinchilla's ampullary nerves.

A morphometric study of the chinchilla's ampullary nerves was conducted to produce an unbiased accounting of the diameter distribution of their constituent fibers. Diameter analyses were determined from 1 microm plastic-embedded nerve sections taken at a plane immediately proximal to the sensory epithelium. We found these nerves to be composed of 2094+/-573 fibers, having diameters that ranged from 0.