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The availability of genetic information, transgenic and knock-out animals make the mouse a primary model in biomedical research. Aminoglycoside ototoxicity, however, has rarely been studied in mature mice because they are considered highly resistant to the drugs. This study presents models for kanamycin ototoxicity in adult CBA/J, C57BL/6 and BALB/c mouse(More)
The mammalian inner ear loses its sensory cells with advancing age, accompanied by a functional decrease in balance and hearing. This study investigates oxidant stress in the cochlea of aging male CBA/J mice. Glutathione-conjugated proteins, markers of H2O2-mediated oxidation, began to increase at 12 months of age; 4-hydroxynonenal and 3-nitrotyrosine,(More)
Transplanting neural stem cells (NSC) to the damaged brain has been regarded as a potential treatment for neurodegenerative diseases such as Alzheimer's disease (AD), a condition characterized by memory loss. We hypothesized that transplantation of NSC into the hippocampal regions of APP + PS1 transgenic (Tg) mice, a well-established model of AD, would(More)
We have previously reported the activation of cell death pathways in the sensory cells of the aging cochlea. Here we investigate age-associated changes in survival mechanisms focusing on phosphatidylinositol 3,4,5-trisphosphate (PIP(3))/Akt signaling. The animal model is the CBA/J mouse of 18 months of age prior to the onset of major functional loss (ABR(More)
Studies over the last decade have left little doubt that reactive oxygen species (ROS) participate in the cellular events leading to aminoglycoside-induced hearing loss. The evidence ranges from the demonstration of aminoglycoside-mediated ROS formation in vitro to the prevention of ototoxicity by antioxidants in guinea pig in vivo. Here we review a(More)
Oxidative stress has been linked to noise- and drug-induced as well as age-related hearing loss. Antioxidants can attenuate the decline of cochlear structure and function after exposure to noise or drugs, but it is debated as to whether they can protect from age-related hearing loss. In a long-term longitudinal study, 10-month-old female CBA/J mice were(More)
The base of the cochlea is more vulnerable to trauma than the apex as seen in the pattern of hair cell damage by cisplatin or aminoglycosides. The differential vulnerability is maintained in organotypic cultures exposed directly to these drugs, suggesting there may be an intrinsic difference in sensitivity to damage along the cochlear spiral. We therefore(More)
We have previously shown gentamicin to form a redox-active iron chelate. This study investigates whether other aminoglycosides can likewise stimulate the generation of reactive oxygen species (free radicals). Kanamycin, neomycin and streptomycin were compared to gentamicin in intact cells and in cell-free in vitro assays using luminescence detection with(More)
We have recently suggested antioxidant therapy against aminoglycoside-induced hearing loss based on the hypothesis of a redox-active aminoglycoside-iron complex causing ototoxicity. The present study compares seven antioxidants and iron chelators for their ability to attenuate gentamicin-induced free radical generation in vitro and ototoxicity in guinea pig(More)
We have previously demonstrated that oxidative stress increases in the inner ear of aging CBA/J mice and might contribute to the loss of function of the sensory system. We now investigate the activation of cell death pathways in the cochleae of these animals. Middle-aged (12 months) and old (18-26 months) mice with hearing deficits displayed outer hair cell(More)