Caspase Inhibitors Promote Vestibular Hair Cell Survival and Function after Aminoglycoside TreatmentIn Vivo

摘要: The sensory hair cells of the inner ear undergo apoptosis after acoustic trauma or aminoglycoside antibiotic treatment, causing permanent auditory and vestibular deficits in humans. Previous studies have demonstrated a role for caspase activation cell death ototoxic injury that can be reduced by concurrent treatment with inhibitors vitro. In this study, we examined protective effects inhibition on vivo systemic injections aminoglycosides. one series experiments, chickens were implanted osmotic pumps administrated pan-caspase inhibitor z-Val-Ala-Asp(Ome)-fluoromethylketone (zVAD) into fluids. One day surgery, animals received 5 d course streptomycin, vestibulotoxic aminoglycoside. Direct infusion zVAD vestibule significantly increased survival streptomycin treatment. A second experiments determined whether rescued could function as receptors. Animals treated displayed system impairment measured greatly vestibulo-ocular response (VOR). contrast, administration had both greater VOR responses, compared alone. These findings suggest inhibiting caspases promotes protects against