Acute withdrawal of exogenous BDNF and NT 3 from spiral ganglion neuron SGN. cell cultures results in apoptosis of the auditory nerves Hh pathway inhibitors. From prior reports, apoptosis of the auditory sensory cells may be eliminated by therapy with either caspase inhibitors w36x or calpain inhibitors w29,58x. These results suggest that participation of calpains and caspases may represent early steps in different apoptotic pathways within the organ of Corti. Hypoxia can be an in vitro model for a few of the conditions that work to make noise induced inner ear damage. It’s been discovered that in guinea pigs subjected to loud broad band sound, the partial pressure of oxygen in the cochlear blood circulation and the perilymph was paid off w25,32,50x. Furthermore, the harm to the organ of Corti triggered by hypoxia and by exposure to loud sound are similar in character w44x. Direct infusion of leupeptin to the scala tympani of animals prior to noise exposure has been shown to partially force away noise induced hearing loss w58x. Other studies have immensely important that calpain plays a job in neuronal death because of hypoxia in other systems w2,6,10,45x. Apoptosis accounts for neuronal death in hypoxic events. Hypoxic nerves present TUNEL labeling, chromatin condensation, Ribonucleic acid (RNA) DNA laddering, and fodrin destruction w6,11x. Calpain inhibitors have now been proven to reduce some of the neuronal death observed in in vitro models of hypoxiarischemia as well as reducing the region of ischemic penumbra in in vivo models of stroke w2,5,6,45x. Our study examines the position of calpain in neurotrophin withdrawal, cisplatin CDDP., and hypoxiainduced apoptosis in dissociated SGN cell cultures and organ of Corti explants. Their protective effects are then compared to those of caspase inhibitors under the same conditions. Fluorescein isothiocyanate conjugated phalloidin FITC phalloidin. Sigma., CDDP Platinol AQ. Bristol Meyers Squibb., and calpain inhibitor I, calpain inhibitor II, and Ac Asp Glu Val Asp GDC-0068 FGFR Inhibitors pNA Ac DEVD pNA. Calbiochem.. Leupeptin was a gift from Dr. A. Stracher Department of Chemistry, SUNY Health Science Center Brooklyn.. Anti neurofilament antibody aNF 66. was a present from Dr. F. H. Chiu Department of Neurology, Albert Einstein College of Medicine.. BOC Asp Ome. Fluoromethyl Ketone T N FMK. Enzyme Systems Products.. All Wistar rats used in these experiments were located within our AAA LAC licensed animal facility and all methods were in accordance with NIH and IACUC directions. Spiral ganglia were dissected from the cochlear ducts of postnatal day 3 P3. Wistar rats Charles River. and placed in to a Petri dish containing 0. 25% trypsin Gibco. and incubated at 378C in a five minutes CO2r95% RH atmosphere for 20 min.