Regeneration of Cochlear Hair Cells and Hearing Recovery

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 […]

HPN-07, a free radical spin trapping agent, protects against functional, cellular and electrophysiological changes in the cochlea induced by acute acoustic trauma

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 […]

siRNA-loaded biodegradable nanocarriers for therapeutic MAPK1 silencing against cisplatin-induced ototoxicity

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 […]

Antioxidants reduce neurodegeneration and accumulation of pathologic Tau proteins in the auditory system after blast exposure

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 […]

Effects of Antioxidant Treatment on Blast-Induced Brain Injury

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 […]

Selective degeneration of synapses in the dorsal cochlear nucleus of chinchilla following acoustic trauma and effects of antioxidant treatment

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 […]

Reduced formation of oxidative stress biomarkers and migration of mononuclear phagocytes in the cochleae of chinchilla after antioxidant treatment in acute acoustic trauma

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 […]

Nitrones as Therapeutics

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 […]

Effectiveness of 4-hydroxy phenyl N-tert-butylnitrone (4-OHPBN) alone and in combination with other antioxidant drugs in the treatment of acute acoustic trauma in chinchilla

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 […]

NAC for noise: From the bench top to the clinic

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 […]

Dispersion of super paramagnetic iron oxide nanoparticles in poly(d,l-lactide-co-glycolide) microparticles

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 […]