Summary Deafness is commonly caused by the irreversible loss of mammalian cochlear hair cells (HCs) due to noise trauma, toxins, or infections. We previously demonstrated that small interfering RNAs (siRNAs) directed against the Notch pathway gene, hairy and enhancer of split 1 (Hes1), encapsulated within biocompatible poly(lactic-co-glycolic acid) nanoparticles (PLGA NPs) could regenerate HCs within ototoxin-ablated murine organotypic cultures. In the […]
Abstract Oxidative stress is considered a major cause of the structural and functional changes associated with auditory pathologies induced by exposure to acute acoustic trauma AAT). In the present study, we examined the otoprotective effects of 2,4-disulfophenyl-N-tert-butylnitrone (HPN-07), a nitrone-based free radical trap, on the physiological and cellular changes in the auditory system of chinchilla following a six-hour exposure […]
Abstract Ototoxicity represents a major adverse side-effect of cis-diamminedichloroplatinum-II (cisplatin, CDDP). The mitogen-activated protein kinase (MAPK) pathway is thought to play a central role in potentiating the apoptotic effect of CDDP within the cochlea. We hypothesized that prophylactic inhibition of MAPK signaling, using small interfering RNA (siRNA), might confer a protective effect against CDDP-induced apoptosis within the auditory sensory […]
Abstract Cochlear neurodegeneration commonly accompanies hair cell loss resulting from aging, ototoxicity, or exposures to intense noise or blast overpressures. However, the precise pathophysiological mechanisms that drive this degenerative response have not been fully elucidated. Our laboratory previously demonstrated that nontransgenic rats exposed to blast overpressures exhibited marked somatic accumulation of neurotoxic variants of the […]
Abstract Blast-induced traumatic brain injury has dramatically increased in combat troops in today’s military operations. We previously reported that antioxidant treatment can provide protection to the peripheral auditory end organ, the cochlea. In the present study, we examined biomarker expression in the brains of rats at different time points (3 hours to 21 days) after […]
Abstract The Notch pathway is a cell signaling pathway determining initial specification and subsequent cell fate in the inner ear. Previous studies have suggested that new hair cells (HCs) can be regenerated in the inner ear by manipulating the Notch pathway. In the present study, delivery of siRNA to Hes1 and Hes5 using a transfection […]
Abstract Exposure to blast overpressure has become one of the hazards of both military and civilian life in many parts of the world due to war and terrorist activity. Auditory damage is one of the primary sequela of blast trauma, affecting immediate situational awareness and causing permanent hearing loss. Protecting against blast exposure is limited […]
Abstract The purpose of this study was to reveal synaptic plasticity within the dorsal cochlear nucleus (DCN) as a result of noise trauma and to determine whether effective antioxidant protection to the cochlea can also impact plasticity changes in the DCN. Expression of synapse activity markers (synaptophysin and precerebellin) and ultrastructure of synapses were examined […]
Abstract We have previously used a three antioxidant combination [4-hydroxy phenyl N-tertbutylnitrone (4-OHPBN), N-acetyl-L-cysteine (NAC), Acetyl-L-carnitine (ALCAR)] to successfully treat acute acoustic trauma (AAT) in chinchilla. However, the mechanistic basis of these antioxidants in treating AAT has not yet been resolved at the cellular and molecular levels. In the present study, we exposed chinchilla to […]
Abstract Nitrones have the general chemical formula X-CH=NO-Y. They were first used to trap free radicals in chemical systems and then subsequently in biochemical systems. More recently several Nitrones including PBN (α-phenyl-tert-butylnitrone) have been shown to have potent biological activity in many experimental animal models. Many diseases of aging including stroke, cancer development, Parkinson’s disease […]
Abstract Acute acoustic trauma (AAT) results in oxidative stress to the cochlea through overproduction of cellular reactive oxygen, nitrogen, and other free radical species appearing from 1 h to 10 days after noise exposure. It has been shown that N-acetyl-L-cysteine (NAC), a glutathione prodrug, and acetyl-L-carnitine (ALCAR), a mitochondrial biogenesis agent, are effective in reducing […]
Abstract Noise-induced hearing loss (NIHL) is an important etiology of deafness worldwide. Hearing conservation programs are in place and have reduced the prevalence of NIHL, but this disorder is still far too common. Occupational and recreational pursuits expose people to loud noise and ten million persons in the US have some degree of noise-induced hearing […]
Abstract Superparamagnetic iron oxide nanoparticles (SPIONs) coated with oleic acid were encapsulated into poly(d,l-lactide-co-glycolide) (PLGA) particles using an oil-in-water-in-oil emulsion technique. The use of the oleic acid-coated SPIONs, and their suspension in the first oil phase led to well-dispersed nanoparticles in the PLGA matrix. Relative amounts of SPIONs encapsulated in PLGA could be varied by […]
