The pathologic similarities noted after ototoxic and/or traumatic injury to the cochlea as well as the key features of the cochlea that make it susceptible to reactive oxygen species (ROS) damage are reviewed. Recent evidence linking ROS to cochlear damage associated with both ototoxins and/or trauma are presented. Mechanisms of generation of ROS in the cochlea and how these metabolites damage the cochlea and impair function are also reviewed. Finally, examples of novel therapeutic strategies to prevent and reverse hearing loss due to noise and/or ototoxins are presented to illustrate the clinical relevance of these new findings.

There is a significant difference in the shape and variability of the perilymph kinetics curve when comparing sustained-release delivery to transtympanic delivery of gentamicin. High early peak levels of gentamicin seen with transtympanic therapy may have a profound effect on the spiral ganglion and produce early HL before obvious hair cell damage. Sustained delivery of gentamicin produces universal HL at 72 hours. The reliability of sustained-release delivery to the ear reduces functional and morphological variations between animals.

The developmental regulation of neurotransmitter synthesis has been extensively studied and appears in many cases to depend on electrical activity. The central nervous system of the Xenopus embryo and young larva is an attractive subject for such studies, since action potentials first elicited from Xenopus spinal neurons at the time of closure of the neural tube are long in duration and calcium-dependent. Moreover, cells exhibit spontaneous elevations of intracellular calcium during this early period as a consequence of calcium influx through voltage-dependent channels, which induces calcium release from intracellular stores. Since the early differentiation of Xenopus spinal neurons in dissociated cell culture parallels development in vivo, we have examined the maturation of gamma-aminobutyric acid (GABA) immunoreactivity in cultured neurons and explored its dependence on spontaneous calcium influx at early stages of development. We find that specific GABA immunoreactivity develops in spinal neurons in dissociated cell culture with the same time course previously defined in vivo. Additionally, this process requires calcium influx that occurs spontaneously through voltage-dependent channels. The appearance of GABA immunoreactivity is blocked by transcriptional inhibitors. The early appearance of GABA raises the possibility that it may play additional roles at early stages of development.

A significant percentage of individuals with motion sickness demonstrate abnormalities in their time constant or vestibulo-spinal reflex function. These abnormalities can be detected using standard, land-based vestibular tests. These preliminary results have implications in understanding the etiology of motion sickness and may provide outcome measures to be used in treating motion sickness.

Results of this study on this group of patients indicate that vertigo can be controlled in the long term using microdose gentamicin without a significant reduction in cochlear or vestibular function in most of the patients in our series. Our results are compared with the published literature examining transtympanic injection. In addition, the underlying science supporting this type of treatment is examined.

No abstract

No abstract

No abstract