Direct Intracochlear Acoustic Stimulation Using a PZT Microactuator.

Combined electric and acoustic stimulation has proven to be an effective strategy to improve hearing in some cochlear implant users. We describe an acoustic microactuator to directly deliver stimuli to the perilymph in the scala tympani. The 800 µm by 800 µm actuator has a silicon diaphragm driven by a piezoelectric thin film (e.

Selective deletion of cochlear hair cells causes rapid age-dependent changes in spiral ganglion and cochlear nucleus neurons.

During nervous system development, critical periods are usually defined as early periods during which manipulations dramatically change neuronal structure or function, whereas the same manipulations in mature animals have little or no effect on the same property. Neurons in the ventral cochlear nucleus (CN) are dependent on excitatory afferent input for survival during a critical period of development. Cochlear removal in young mammals and birds results in rapid death of target neurons in the CN.

Changes in the adult vertebrate auditory sensory epithelium after trauma.

Auditory hair cells transduce sound vibrations into membrane potential changes, ultimately leading to changes in neuronal firing and sound perception. This review provides an overview of the characteristics and repair capabilities of traumatized auditory sensory epithelium in the adult vertebrate ear. Injured mammalian auditory epithelium repairs itself by forming permanent scars but is unable to regenerate replacement hair cells.

Inhibition of Notch activity promotes nonmitotic regeneration of hair cells in the adult mouse utricles.

The capacity of adult mammals to regenerate sensory hair cells is not well defined. To explore early steps in this process, we examined reactivation of a transiently expressed developmental gene, Atoh1, in adult mouse utricles after neomycin-induced hair cell death in culture. Using an adenoviral reporter for Atoh1 enhancer, we found that Atoh1 transcription is activated in some hair cell progenitors (supporting cells) 3 d after neomycin treatment.

p27(Kip1) is required to maintain proliferative quiescence in the adult cochlea and pituitary.

Cell cycle inhibitors, such as the cyclin-dependent kinase (Cdk) inhibitor proteins and retinoblastoma (Rb) family members, control exit from the cell cycle during the development of a variety of terminally differentiated tissues. It is unclear whether sustained expression of these proteins is required to prevent cell cycle re-entry in quiescent and terminally differentiated cells. The organ of Corti (cochlear sensory epithelium) and pars intermedia (intermediate lobe of the pituitary) are two tissues that share the characteristic of ongoing cell division in mice lacking either the p27(Kip1) Cdk inhibitor, Ink4 proteins, or Rb.

Deafness and retinal degeneration in a novel USH1C knock-in mouse model.

Usher syndrome is the leading cause of combined deaf-blindness, but the molecular mechanisms underlying the auditory and visual impairment are poorly understood. Usher I is characterized by profound congenital hearing loss, vestibular dysfunction, and progressive retinitis pigmentosa beginning in early adolescence. Using the c.

Activin potentiates proliferation in mature avian auditory sensory epithelium.

Humans and other mammals are highly susceptible to permanent hearing and balance deficits due to an inability to regenerate sensory hair cells lost to inner ear trauma. In contrast, nonmammalian vertebrates, such as birds, robustly regenerate replacement hair cells and restore hearing and balance functions to near-normal levels. There is considerable interest in understanding the cellular mechanisms responsible for this difference in regenerative capacity.

Supporting cell characteristics in long-deafened aged mouse ears.

Significant sensory hair cell loss leads to irreversible hearing and balance deficits in humans and other mammals. Future therapeutic strategies to repair damaged mammalian auditory epithelium may involve inserting stem cells into the damaged epithelium, inducing non-sensory cells remaining in the epithelium to transdifferentiate into replacement hair cells via gene therapy, or applying growth factors. Little is currently known regarding the status and characteristics of the non-sensory cells that remain in the deafened auditory epithelium, yet this information is integral to the development of therapeutic treatments.

Cellular targets of estrogen signaling in regeneration of inner ear sensory epithelia.

Estrogen signaling in auditory and vestibular sensory epithelia is a newly emerging focus propelled by the role of estrogen signaling in many other proliferative systems. Understanding the pathways with which estrogen interacts can provide a means to identify how estrogen may modulate proliferative signaling in inner ear sensory epithelia. Reviewed herein are two signaling families, EGF and TGFbeta.

Sox2 and JAGGED1 expression in normal and drug-damaged adult mouse inner ear.

Inner ear hair cells detect environmental signals associated with hearing, balance, and body orientation. In humans and other mammals, significant hair cell loss leads to irreversible hearing and balance deficits, whereas hair cell loss in nonmammalian vertebrates is repaired by the spontaneous generation of replacement hair cells. Research in mammalian hair cell regeneration is hampered by the lack of in vivo damage models for the adult mouse inner ear and the paucity of cell-type-specific markers for non-sensory cells within the sensory receptor epithelia.

Expression of LHX3 and SOX2 during mouse inner ear development.

A cascade of transcription factors is believed to regulate the coordinate differentiation of primordial inner ear cells into the subtypes of hair cells and supporting cells. While candidate genes involved in this process have been identified, the temporal and spatial patterns of expression of many of these have not been carefully described during the extended period of inner ear development and functional maturation. We systematically examined the expression of two such transcription factors, LHX3 and SOX2, from the time of hair cell terminal mitoses into adulthood.

Treatment of Parkinson's disease: a survey of patients and neurologists.

Background: The treatment of Parkinson's disease (PD) is complex and highly individual. The choice between available treatment options depends on clinical characteristics such as the patient's age, disease severity and presence of comorbidities, lifestyle characteristics and preferences, costs of different medications and awareness and perception of available treatment options, and education of the treating physician. The impact of PD treatment regimens on patients' health-related quality of life (QOL) is also an important healthcare feature.

Expression of Prox1 during mouse cochlear development.

We carried out an analysis of the expression of Prox1, a homeo-domain transcription factor, during mouse inner ear development with particular emphasis on the auditory system. Prox1 is expressed in the otocyst beginning at embryonic day (E)11, in the developing vestibular sensory patches. Expression is down regulated in maturing (myosin VIIA immunoreactive) vestibular hair cells and subsequently in the underlying support cell layer by E16.

Characterization of leukocyte subtypes in chicken inner ear sensory epithelia.

Human hearing and balance require intact inner ear sensory hair cells, which transduce mechanical stimuli into electrical signals that are transmitted to the brain. Loss of hair cells after birth in mammals is irreversible, whereas birds are able to regenerate hair cells after insult and demonstrate ongoing hair cell production in the vestibular epithelia. Leukocytes reside in undamaged sensory epithelia of the avian inner ear and increase in number after trauma, prior to the proliferation of hair cell progenitors.

ErbB expression: the mouse inner ear and maturation of the mitogenic response to heregulin.

In humans, hair cell loss often leads to hearing and balance impairments. Hair cell replacement is vigorous and spontaneous in avians and nonmammalian vertebrates. In mammals, in contrast, it occurs at a very low rate, or not at all, presumably because of a very low level of supporting cell proliferation following injury.

Ultrastructural analysis of [3H]thymidine-labeled cells in the rat utricular macula.

Ototoxic drugs stimulate cell proliferation in adult rat vestibular sensory epithelia, as does the infusion of transforming growth factor alpha (TGFalpha) plus insulin. We sought to determine whether new hair cells can be regenerated by means of a mitotic pathway. Previously, studies have shown that the nuclei of some newly generated cells are located in the lumenal half of the sensory epithelium, suggesting that some may be newly generated sensory hair cells.

Characterization of damage and regeneration in cultured avian utricles.

Hair cell regeneration occurs spontaneously throughout life and following hair cell injury in the vestibular epithelia of mature birds and other nonmammalian vertebrates. We examined hair cell regeneration in post-hatch chick utricles that were cultured in media with or without the ototoxin, streptomycin, for various periods. The goal of our study was to characterize the dose- and time-dependent effects of streptomycin on hair cell loss and regeneration in vitro.

Basic fibroblast growth factor inhibits cell proliferation in cultured avian inner ear sensory epithelia.

Postembryonic production of inner ear hair cells occurs after insult in nonmammalian vertebrates. Recent studies suggest that the fibroblast family of growth factors may play a role in stimulating cell proliferation in mature inner ear sensory epithelium. Effects of acidic fibroblast growth factor (FGF-1) and basic fibroblast growth factor (FGF-2) were tested on progenitor cell division in cultured auditory and vestibular sensory epithelia taken from posthatch chickens.

Growth factor regulation of the cell cycle in developing and mature inner ear sensory epithelia.

Growth factors and other extracellular signals regulate cell division in many tissues. Consequently, growth factors may have therapeutic uses to stimulate the production of replacement sensory hair cells in damaged human inner ears, thereby assisting in alleviating hearing loss and vestibular dysfunction. Assessment of the ability of growth factors to stimulate cell proliferation in inner ear sensory epithelia is at an early stage.

Transforming growth factor alpha with insulin stimulates cell proliferation in vivo in adult rat vestibular sensory epithelium.

Hair cells, the sensory receptors of the mammalian inner ear, have long been thought to be produced only during embryogenesis, and postnatal hair cell loss is considered to be irreversible and is associated with permanent hearing and balance deficits. Little is known about the factors that regulate hair cell genesis and differentiation. The mitogenic effects of insulin and transforming growth factor alpha (TGFalpha) were assayed in vivo in normal and drug-damaged rat inner ear.

Macrophage and microglia-like cells in the avian inner ear.

Recent studies suggest that macrophages may influence early stages of the process of hair cell regeneration in lateral line neuromasts; numbers of macrophages were observed to increase prior to increases in hair cell progenitor proliferation, and macrophages have the potential to secrete mitogenic growth factors. We examined whether increases in the number of leukocytes present in the in vivo avian inner ear precede the proliferation of hair cell precursors following aminoglycoside insult. Bromodeoxyuridine (BrdU) immunohistochemistry was used to identify proliferating cells in chicken auditory and vestibular sensory receptor epithelia.

Transforming growth factor-alpha with insulin induces proliferation in rat utricular extrasensory epithelia.

Hair cell loss in the human inner ear leads to sensorineural hearing loss and vestibular dysfunction. Recent studies suggest that exogenous addition of growth factors, for example, transforming growth factor-alpha with insulin, may stimulate the production of new supporting cells and hair cells in the mature mammalian vestibular sensory epithelium. Before any growth factor can be seriously considered for the treatment of clinical problems related to hair cell loss, its effects on the extrasensory epithelia must also be fully explored.

Recent insights into regeneration of auditory and vestibular hair cells.

Advances in hair cell regeneration are progressing at a rapid rate. This review will highlight and critique recent attempts to understand some of the cellular and molecular mechanisms underlying hair cell regeneration in non-mammalian vertebrates and efforts to induce regeneration in the mammalian inner ear sensory epithelium.

RadNotes: a novel software development tool for radiology education.

RadNotes is a novel software development tool that enables physicians to develop teaching materials incorporating text and images in an intelligent, highly usable format. Projects undertaken in the RadNotes environment require neither programming expertise nor the assistance of a software engineer. The first of these projects, Thoracic Imaging, integrates image teaching files, concise disease and topic summaries, references, and flash card quizzes into a single program designed to provide an overview of chest radiology.

Induction of cell proliferation in avian inner ear sensory epithelia by insulin-like growth factor-I and insulin.

Postembryonic production of inner-ear hair cells occurs both normally and after insult in lower vertebrates and avians. To determine how this proliferation is controlled, several growth factors were tested for effects on progenitor-cell division in cultured avian vestibular sensory epithelium. Mitogenic effects of bombesin, epidermal growth factor, insulin-like growth factor-I (IGF-I), insulin, and transforming growth factor-alpha were assayed in organo-typic cultures of utricles from the mature, undamaged (normal) chicken inner ear.