Role of fibroblast growth factor 8 in neurite outgrowth from spiral ganglion neurons in vitro.

Many neurons degenerate after injuries resulting from overstimulation, drugs, genetic mutations, and aging. Although several growth factors and neurotrophins delay degeneration and promote regrowth of neural processes, the role of fibroblast growth factor 8 (FGF8) in mammalian spiral ganglion neurons (SGN) neurite outgrowth has not been examined. This study develops and uses SGN cell cultures suitable for experimental analysis, it investigates whether FGF8a and FGF8b isoforms affect the neurite outgrowth from SGN cultured in vitro.

Degeneration in the ventral cochlear nucleus after severe noise damage in mice.

To study the mechanisms of noise-induced hearing loss and the phantom noise, or tinnitus, often associated with it, we used a mouse model of noise damage designed for reproducible and quantitative structural analyses. We selected the posteroventral cochlear nucleus, which has shown considerable plasticity in past studies, and correlated its changes with the distribution of neurotrophin 3 (NT3). We used volume change, optical density analysis, and microscopic cluster analysis to measure the degeneration after noise exposure.

Postnatal development of NT3 and TrkC in mouse ventral cochlear nucleus.

In the developing nervous system, neurotrophin 3 (NT3) and brain-derived neurotrophic factor (BDNF) have been shown to interact with each other and with different parts of a neuron or glia and over considerable distances in time and space. The auditory system provides a useful model for analyzing these events, insofar as it is subdivided into well-defined groups of specific neuronal types that are readily related to each other at each stage of development. Previous work in our laboratory suggested that NT3 and its receptor TrkC in the mouse cochlear nucleus (CN) may be involved in directing neuronal migration and initial targeting of inputs from cochlear nerve axons in the embryo.

Inactivation of fibroblast growth factor receptor signaling in myelinating glial cells results in significant loss of adult spiral ganglion neurons accompanied by age-related hearing impairment.

Hearing loss has been attributed to many factors, including degeneration of sensory neurons in the auditory pathway and demyelination along the cochlear nerve. Fibroblast growth factors (FGFs), which signal through four receptors (Fgfrs), are produced by auditory neurons and play a key role in embryonic development of the cochlea and in neuroprotection against sound-induced injury. However, the role of FGF signaling in the maintenance of normal auditory function in adult and aging mice remains to be elucidated.

Cisplatin-induced ototoxicity: effect of intratympanic dexamethasone injections.

Hypothesis: Intratympanic (IT) application of dexamethasone will reduce ototoxicity associated with systemic cisplatin therapy.

Background: Cisplatin is a common chemotherapeutic drug often dose-limited by ototoxicity attributed to the formation of reactive oxygen and nitrogen species damaging critical inner ear structures. Steroids have been shown to reduce formation of reactive oxygen species and thus may reduce ototoxicity.