Maoli Duan

Dose and time-dependent protection of the antioxidant N-l-acetylcysteine against impulse noise trauma

Noise-induced hearing loss is one of the most common causes of hearing disability, and at present there is no effective biological protection or cure. Firearms and some industrial equipment can generate very high levels of impulse noise, which is known to cause sensorineural hearing loss. It has been shown that antioxidants such as N-L-acetylcysteine (NAC) can protect the inner ear from oxidative damage. The present study investigates whether NAC (i.p.) can protect the cochlea from impulse noise trauma. Rats were exposed to 50 noise pulses at 160 dB SPL peak value. Electrophysiological hearing thresholds were assessed with auditory brainstem response (ABR) up to 4 weeks after noise exposure. Animals exposed to impulse noise, without treatment of NAC, had larger threshold shifts in the frequency range 4-40 kHz than animals injected with NAC. Hair cell loss was significantly reduced using a schedule of three NAC injections in the rats. These results suggest that NAC can partially protect the cochlea against impulse noise trauma.

Xenografted fetal dorsal root ganglion, embryonic stem cell and adult neural stem cell survival following implantation into the adult vestibulocochlear nerve

Sensorineural hearing loss is a disabling condition. In the post-embryonic and adult mammalian inner ear, the regeneration of auditory hair cells, spiral ganglion neurons or their axons does not occur naturally. This decrease in excitable neurons limits the success of auditory rehabilitation. Allografts and xenografts have shown promise in the treatment of a variety of neurological diseases. Fetal dorsal root ganglion (DRG) neurons can extend functional connections in the rat spinal cord. Embryonic stem cells (ES cells) and adult neural stem cells (ANSC) have the potential to differentiate into neurons. We have implanted embryonic days (E) 13-16 fetal mouse DRGs from transgenic mouse lines that express Enhanced Green Fluorescent Protein (EGFP) or lacZ reporter genes, EGFP-expressing ES cells or lacZ-expressing ANSC into the injured vestibulocochlear nerve of adult rats and guinea pigs. Survival of the implants was assessed 2 to 4 weeks postoperatively. For further evaluation of the differentiation of the implanted ES-cells, we double labeled with the mouse-specific neuronal antibody Thy 1.2. The rats implanted with EGFP- or lacZ-expressing DRGs showed labeled DRGs after sacrifice. In addition, EGFP-positive nerve fibers were seen growing within the proximal nerve. The results from the EGFP ES cells and lacZ ANSC revealed reporter-expressing cells at the site of injection in the vestibulocochlear nerve of the host rats and guinea pigs but also within the brain stem. Thy 1.2 profiles were seen among the EGFP ES cells within the 8th cranial nerve. The findings of this study indicate that the vestibulocochlear nerve of adult rats and guinea pigs will support xenotransplants of embryonic DRG, ES cells and ANSC. This may have future clinical applicability in recreating a neuronal conduit following neuronal injury between the inner ear and the central nervous system (CNS).

Extracranial and intracranial complications of otitis media: 22-year clinical experience and analysis.

Abstract Conclusion: The morbidity of the complications has had a decreased tendency in recent decades, but the category of the complications was rather diverse. There are still many serious complications that require our attention. Surgery is still the most important treatment option. Objective: To investigate otogenic extracranial and intracranial complications in patients with acute and chronic otitis media. Methods: A retrospective study investigated 285 patients with extracranial and intracranial complications among the 2346 inpatients with acute or chronic otitis media with or without cholesteatoma admitted to the Department of Otolaryngology, AnHui Medical University Hospital between 1987 and 2008. Results: In the 285 patients with cranial complications, 253 had a single complication, 29 had two complications, and 3 had more than two complications. Intracranial complications included meningitis (16 cases), brain abscess (42 cases), sigmoid sinus involvement (29 cases), extradural abscess (8 cases), subdural abscess (1 case), and hydrocephalus (2 cases). Extracranial complications included labyrinthitis (90 cases), mastoid abscess (79 cases), facial paralysis (47 cases), Bezold abscess (5 cases), and apicitis pyramidalis (1 case). In all, 267 patients were cured or improved without recurrence. Five patients died from complications, of whom four died of cerebral hernia and one died of multiple abscesses.

A cell therapy approach to substitute neural elements in the inner ear

Three different donor tissues were tested for their capacity to survive, integrate and differentiate in the adult inner ear. Surviving embryonic dorsal root ganglion cells were found within the spiral ganglion neuron region and along the auditory nerve fibers. In the presence of exogenous nerve growth factor (NGF), the dorsal root ganglion cells formed extensive growth of neurites that seemed to contact the host neurons. Adult neural stem cells survived relative poorly in the inner ear whereas embryonic stem cells showed a somewhat greater capacity for survival and integration. Overall, the survival rate of implanted tissue was quite low in the cochlea. It is concluded that an inner ear cell therapy approach based on the implantation of exogenous cells will require that important survival factors are identified and supplied. In addition, it is possible that the physical properties of the cochlea, e.g., fluid-filled compartments and very limited space for cell proliferation, are unfavorable, at least in the normal cochlea.

Imaging of the guinea pig cochlea following round window gadolinium application

Precise, non-invasive determination of the aetiology and site of pathology of inner ear disorders is difficult. The aim of this study was to describe an alternative method for inner ear visualization, based on local application of the paramagnetic contrast agent gadolinium. Using a 4.7 T MRI scanner, high contrast images of all four cochlear turns were obtained 3.5 h after placing gadolinium on the round window membrane. Gadolinium cleared from the cochlea within 96 h. Auditory brainstem response measurements performed on a separate group of animals showed no significant threshold shifts after the application, indicating that gadolinium is non-toxic to the guinea pig cochlea.

Acute treatment of noise trauma with local caroverine application in the guinea pig.

Intense sound stimulation may result in excessive glutamate release from the inner hair cells, resulting in binding to the post-synaptic glutamate receptors and leading to neuronal degeneration and functional impairment. In this study we investigated the therapeutic effect and time window of caroverine, an N-methyl-D-aspartate and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antagonist, on noise-induced hearing loss. Guinea pigs were exposed to one-third octave band noise centered at 6.3 kHz (110 dB sound pressure limit) for 1 h. One or 24 h after noise exposure, caroverine was applied to the round window membrane. Auditory brainstem responses were recorded at regular time intervals. It was shown that caroverine could significantly decrease hearing impairment after noise trauma when applied 1 but not 24 h after noise exposure.

Pharmacokinetics of Caroverine in the Inner Ear and Its Effects on Cochlear Function after Systemic and Local Administrations in Guinea Pigs

Caroverine, an N-methyl-D-aspartate and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antagonist, has been shown to protect the inner ear from excitotoxicity and to be effective in the treatment of cochlear synaptic tinnitus. Local administration of caroverine on the round window membrane (RWM) could be a more effective means of administration to avoid systemic side/adverse effects. The present study investigates the pharmacokinetics of caroverine in the perilymph, cerebrospinal fluid (CSF) and plasma following intravenous and local applications at different dosages. High-performance liquid chromatography was used to determine the drug concentrations. Our results show much higher caroverine concentrations in the perilymph with lower concentrations in CSF and plasma following local applications compared with systemic administration. Auditory brainstem responses were measured to evaluate the changes in auditory function. The effects on hearing were transient and fully reversible 24 h after local caroverine applications. The findings suggest that local application of caroverine on the RWM for the treatment of excitotoxicity-related inner ear diseases, such as tinnitus and noise-induced hearing loss, might be both safe and more efficacious while avoiding high blood and CSF caroverine levels seen with systemic administration.

Protection of auditory function against noise trauma with local caroverine administration in guinea pigs

Glutamate is the most likely neurotransmitter at the synapse between the inner hair cell and its afferent neuron in the peripheral auditory system. Intense noise exposure may result in excessive glutamate release, binding to the post-synaptic receptors and leading to neuronal degeneration and hearing impairment. The present study investigated the protective effect of caroverine, an antagonist of two glutamate receptors, N-methyl-D-aspartate and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, on noise-induced hearing loss. Two different doses of caroverine were applied onto the round window membrane with gelfoam, followed by one-third-octave band noise centered at 6.3 kHz (110 dB SPL) for 1 h. Auditory brainstem responses were measured at regular time intervals afterwards. Caroverine was found to offer significant protection of the cochlear function against noise-induced hearing loss.

A clinical study of microcirculatory disturbance in Chinese patients with sudden deafness.

Conclusion. Cochlear microcirculation disturbance is closely associated with sudden deafness. Objectives. To investigate the relationship between cochlear microcirculation and sudden deafness. Subjects and methods. Clinical laboratory parameters (clinical chemistry, hemorheology, hematology, and hemostasis determinations) were studied in 86 patients with sudden deafness and 30 healthy control subjects. Results. The levels of total cholesterol (TCH), triglyceride (TG), and lipoprotein A were significantly higher in patients with sudden deafness than in control subjects. Plasma viscosity, ratio viscosity of whole blood, reduced viscosity of whole blood, high and low shear relative viscosity of whole blood, index of red blood cells transmutation, and fibrinogen level in the plasma of patients with sudden sensorineural hearing loss (SSNHL) were also significantly elevated in comparison with those in control subjects. White-collar workers with psychological and behavioral abnormalities tend to suffer from sudden deafness.

Evaluation of the noise generated by otological electrical drills and suction during cadaver surgery.

Abstract Conclusion. Noise levels sufficient to cause sensorineural hearing loss can be measured when electrical drills and suction are used during otological surgery, particularly if a running burr touches the endosteal membrane of the otic capsule. Our noise measurements confirm the theory that ‘soft surgery’ should be employed during otological surgery, with focus on reduction of noise exposure. Objective: To investigate noise levels generated by otological electrical drills and suction. Methods: Airborne noise levels generated by different drills and suction tips of different diameters were evaluated in 12 fresh isolated human temporal bones by means of an ER7C probe microphone system. Results: Noise levels ranged from 120 to 122 dB SPL during drilling in cortical bone and from 117 to 121 dB SPL during drilling in the mastoid cavity. There was no statistically significant difference between cutting and diamond burrs (p > 0.05). Noise levels during cochleostomy ranged from 116 to 131 dB SPL. Noise levels recorded in the round window exceeded 130 dB SPL when the endosteal membrane was touched by the burr. Noise levels generated by various types of suctions ranged from 100 to 129 dB SPL and a positive significant relation was found between noise and increased luminal diameter of the suction tip up to a diameter of 2 mm.