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PubMed1997

High-resolution CT of the temporal bone in dysplasia of the auricle and external auditory canal.

PURPOSE: To determine CT findings in the external, middle, and inner ear of patients with microtia and external auditory canal dysplasia. METHODS: We used high-resolution CT, with multiplanar or axial 1-mm continuous sections, coronal or sagittal reformations, or low-dose spiral acquisitions, to examine 184 temporal bones of children with microtia. RESULTS: In cases of minor microtia, auditory canal stenosis was the most common associated abnormality; in those with major microtia, atresia was predominant. Middle ear malformations depended on the severity of the auricular anomalies. Inner ear changes could also be noted. Ossicle dysplasias occurred in 98% of patients (stapes, 72%), absence of the oval window in 36%, labyrinthine malformations in 13%, closed round window in 6%, facial canal displacement in up to 75%, and aberrations of the vascular canal in 38% of patients with third-grade auricular deformity. CONCLUSION: A variety of external, middle, and, less frequently, inner ear changes were detected in connection with microtia.

Abnormalities, Multiple↗
PubMed2006

Does erythropoietin augment noise induced hearing loss?

Noise-induced hearing loss may result from excessive release of glutamate, nitrogen oxide and reactive oxygen species. The effects of these factors on the inner ear may potentially be prevented or reduced by erythropoietin (EPO), as indicated by previously demonstrated neuro-protective effects of EPO upon damage to the central nervous system and the retina. This paper reports three separate trials, conducted to investigate the hypothesis that noise-induced hearing loss is prevented or reduced by erythropoietin. The trials employed three different modes of drug application, different administration time windows and different rodent species. In trial 1, guinea pigs were exposed to 110dB SPL, 4-20kHz wide band noise (WBN) for 8h. EPO was administered to the round window membrane 24h after noise exposure, either sustained by pump for a week or by single dose middle ear instillation. In trial 2, rats were exposed to 105dB SPL, 4-20kHz WBN for 8h. EPO was administered by single dose middle ear instillation 1 or 14h after noise exposure. In trial 3, rats were exposed to 105dB SPL, 4-20kHz WBN for 8 or 3x8h. EPO was injected intraperitoneally 1h before noise exposure. Oto-acoustic emissions and auditory brainstem responses (at 16kHz) were recorded before and after noise exposure in all trials. The noise exposure induced a hearing loss in all animals. In trial 1, no recovery and no improvement of hearing occurred in any treatment group. In trial 2 and 3, a partial hearing recovery was seen. However, the hearing loss of the EPO treated animals was significantly worse than controls in trial 2. In trial 3, the hearing of the EPO treated animals exposed for 3x8h was significantly worse than controls. Thus, surprisingly, the results from 2 of the 3 present trials indicate that erythropoietin may in fact augment noise-induced hearing loss. This is contradictory to the beneficial effect of EPO reported by the vast majority of studies on stressed neural tissues. EPO administration may alter the blood flow dynamics of the cochlear vascular bed during or after noise exposure, by a potential induction of vasoconstriction. This may be the cause of the surprising findings.

Animals↗
PubMed2002

Cochlear delivery of fibroblast growth factor 1 and its effects on apoptosis and cell cycling in noise-exposed guinea pig ears.

OBJECTIVES: Acidic fibroblast growth factor 1 (FGF-1) is a mitogen and antiapoptotic factor synthesized by cochlear neurons and transported to the organ of Corti. The objectives of this investigation were threefold: (1) to develop an animal model to study the cochlear effects of intratympanic delivery of FGF-1; (2) to determine the distribution, in the mature mammalian cochlea, of FGF-1 and the receptor, FGFR3, to which it binds with high affinity; and (3) to examine the effect of exogenous FGF-1 on cochlear apoptotic and cell-cycling markers in noise and non-noise-exposed guinea pigs ears. METHODS: Fifteen adult Hartley guinea pigs were divided into three groups. Group 1 animals (n = 5) underwent direct placement of FGF-1 in phosphate buffered saline (PBS) (20 pg/mL) soaked Gelfoam pledgets to the right round window membrane. Phosphate buffered saline-soaked Gelfoam pledgets were placed on the left round window membrane as a control. In group 2 animals (n = 5), surgical placement of either FGF-1 or PBS was followed by exposure to 120 dB of white noise for 2 hours. Group 3 animals (n = 5) were subjected to identical noise conditions prior to undergoing round window application of either FGF-1 or PBS. All groups were allowed to recover in a noise-controlled environment for 12 hours following surgery. Anti-FGF-1-stained Western blots and optical densitometry analyses were used to quantitate passage of FGF-1 into cochlear perilymph. Standard in situ immunohistochemical techniques were used to stain each cochlea for FGF-1 and FGFR3, apoptotic markers p53 and p21, Bcl-2, and the cell-cycling marker proliferating cell nuclear antigen (PCNA). Tissue sections were subjected to the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labelling technique (TUNEL) for apoptosis. RESULTS: Western blot and optical densitometry analyses of cochlear perilymph showed increased concentrations of FGF-1 in 10 of 14 experimental cochleas. Cochlear perilymph FGF-1 was consistently bound to heparan sulphate proteoglycan (HSPG). Immunoreactivity of both FGF-1 and FGFR3 was observed in spiral ganglion neurons, inner and outer hair cells, pillar cells, and Dieter and Hensen's cells. Specific FGF-1 immunostaining to the distal portion of the pars pectinata of the basilar membrane was noted in noise-exposed animals only. Bcl-2 and PCNA immunostaining was not detected in any group. There was no significant nuclear immunoreactivity to proapoptotic markers, p53 and p21, in any group. Semiquantitative analysis of TUNEL staining in block sections of all cochleas demonstrated a 340% increase in nuclear immunoreactivity of noise-exposed outer hair cells and organ of Corti cells. There was no difference between FGF-1 treated and control ears subjected to TUNEL staining. CONCLUSIONS: Exogenous FGF-1 crosses the round window membrane and is bound to HSPG in cochlear perilymph. The specific immunoreactivity of the pars pectinata to FGF-1 may represent a unique reservoir for cochlear FGF-1 in noise-exposed ears of the guinea pig. Noise induces apoptosis of organ of Corti cells as demonstrated with the TUNEL technique. PCNA, Bcl-2, p53, and p21 in noise-exposed and non-noise-exposed guinea pig cochleas are not affected by exogenous FGF-1. Noise-induced hair cell apoptosis appears to be independent of the p53 pathway. Lack of immunoreactivity to Bcl-2 supports the concept that the apoptotic mechanism is likely to involve C-Jun-N-terminal kinase- or caspase-dependent pathways. Exogenous FGF-1 does not alter apoptosis or cell cycling in the mature guinea pig cochlea within 12 hours of acute acoustic trauma.

Animals↗
PubMed1995

[Measurement of cochlear blood flow during exploratory tympanotomy in patients suspected of having perilymphatic fistulas].

Since impairment of cochlear blood flow is one of the factors implicated in the pathophysiology of sudden deafness, we measured cochlear blood flow in nine patients suspected of having perilymphatic fistulas. All but one patient had sudden sensorineural hearing loss. The exceptional case had experienced rotatory vertigo immediately after nose-blowing. In the eight patients with sudden deafness, the average hearing level ranged from 30dB to 80dB. Among these patients, there was a first reported case of recurrent inner ear barotrauma due to diving. This case was a 41-year-old male who had a second episode of sudden deafness six years after the first sudden deafness episode affecting the same ear. During exploratory tympanotomy, the tip of a laser-Doppler probe was attached to the promontory near the anterior superior portion of the round window niche. The outer diameter of the probe was 1.7mm and the distance between the exciting and receiving optic fibers was 1.0mm. Pulsatory movement of the laser-Doppler output was observed in all 9 patients even after the middle ear mucosa had been removed. We attempted to measure the effects of carbon dioxide on cochlear blood flow, using methods such as inhalation of carbogen and cessation of respiration. In most cases, however, no significant change in cochlear blood flow was observed with these procedures.

Adult↗
PubMed2006

Magnetic nanoparticles: inner ear targeted molecule delivery and middle ear implant.

Superparamagnetic iron oxide nanoparticles (SNP) composed of magnetite (Fe(3)O(4)) were studied preliminarily as vehicles for therapeutic molecule delivery to the inner ear and as a middle ear implant capable of producing biomechanically relevant forces for auditory function. Magnetite SNP were synthesized, then encapsulated in either silica or poly (D,L,-Lactide-co-glycolide) or obtained commercially with coatings of oleic acid or dextran. Permanent magnetic fields generated forces sufficient to pull them across tissue in several round window membrane models (in vitrocell culture, in vivo rat and guinea pig, and human temporal bone) or to embed them in middle ear epithelia. Biocompatibility was investigated by light and electron microscopy, cell culture kinetics, and hair cell survival in organotypic cell culture and no measurable toxicity was found. A sinusoidal magnetic field applied to guinea pigs with SNP implanted in the middle ear resulted in displacements of the middle ear comparable to 90 dB SPL.

Animals↗
PubMed2001

Ventral approach to the rat middle ear for otologic research.

OBJECTIVE: To describe a simple approach to the rat middle ear because there are few clear descriptions of this technique with minimal morbidity and mortality. STUDY DESIGN AND SETTING: Six male Long-Evans rats were used in this study. We designed a cervical approach to the middle ear with the purpose of creating an experimental model of ossiculoplasty that permits the postoperative survival of the animal. RESULTS: It was possible in all cases to visualize the majority of structures of the tympanic cavity: promontory, round window, stapedial artery, stapes, incus, and tympanic membrane. There were no cases of postoperative infection or facial paralysis. CONCLUSIONS AND SIGNIFICANCE: The ventral approach to the rat middle ear is a rapid and simple technique that makes the rat the animal of choice for many otologic investigations.

Animals↗
PubMed1997

Local effects of nitric oxide on vestibular blood flow in the Mongolian gerbil.

There is a paucity of studies regarding the regulation of vestibular blood flow (VBF), despite the possibility that vascular alterations may contribute to specific vestibulopathies. The current experiments used the Mongolian gerbil as an animal model since it provides easy surgical access to the vestibular end-organs and has been previously used for physiologic studies involving inner ear function. VBF changes were measured in the posterior semicircular canal using laser Doppler flowmetry following round window membrane (RWM) application of the nitric oxide donor 1, 3-propanediamine-N-[4-1-(3-aminopropyl)-2-hydroxy-2-nitrosohydrazi no] butyl (spermine NONOate; SPNO) as a vasodilator. The specificity of the responses induced was tested via pretreatment with an NO scavenger, 2-(4-Carboxyphenyl)-4,4,5,5-tetramethylimidazonline-1-oxyl-3-oxide (carboxy-PTIO; cPTIO). cPTIO, SPNO, vehicle (control) or cPTIO/SPNO were applied to the RWM, during which blood pressure and VBF were monitored for baseline, treatment, and recovery conditions. Results showed concentration-dependent increases in flow, probably resulting from NO's vasodilatory action on local vasculature. cPTIO pretreatment was found to attenuate SPNO-induced VBF increases. These findings support a role of NO in maintaining the vestibular microcirculation.

Animals↗
PubMed1996

Tuning curves of the difference tone auditory nerve neurophonic.

When a pair of tonal stimuli of different frequencies (F1 and F2, where F2 > F1) are simultaneously presented to the ear, an electrical response with a frequency of F2-F1 can be recorded from the round window (RW) of the gerbil's cochlea. By using phase-locked tones of alternating polarity, the cochlear microphonics are canceled, leaving a time-averaged difference tone-auditory nerve neurophonic (DT-ANN). When the F1 frequency ranges from 1.25 to 30 kHz and F2-F1 approximately 900 Hz, a DT-ANN audiogram can be constructed which parallels (but is at least 10 dB more sensitive than) the compound action potential (CAP) audiogram. In addition to this DT response, a smaller magnitude, higher threshold response having a frequency of 2 DT can often be measured. Both the DT-ANN and the 2 DT-ANN show non-monotonic amplitude input-output functions. The DT- and 2 DT-ANN responses can be forward masked. Masking of low level (e.g., 30 dB SPL) probe stimuli results in DT- and 2 DT-ANN V-shaped tuning curves (TC) with low tip thresholds (approximately 20-30 dB SPL) and a tip frequency close to that of F1 and F2. The Q10 dB values of the forward masked DT-ANN TCs ranges from 1.54 to 20.0 for F1 frequencies varying from 2 to 20 kHz, respectively. The V-shaped DT-ANN TCs generated with simultaneous maskers are often flanked, outside their high- and low-frequency slopes, by frequency-intensity domains where the masker enhances the amplitude of the DT-ANN response. These data (1) provide evidence that, in response to low-intensity tones, the DT-ANN is generated by a restricted population of neurons that have characteristic frequencies close to F1 and F2, and (2) provide evidence for sharply tuned, phase-locked activity occurring in response to low-intensity stimuli, by cochlear axons having characteristic frequencies as high as 20 kHz.

Acoustic Stimulation↗
PubMed1991

Anatomic variations and anomalies involving the facial canal.

Congenital bony dehiscences in the facial canal result from incomplete closure during development and are observed in approximately 55% of temporal bones. Anomalies involving the facial canal frequently are encountered in malformations of the temporal bone. These anomalies include aberrations of the course of one or all of the segments of the canal; abnormal relation to the oval and round window; bifurcations and trifurcations of the nerve; and associations with dysplasia of the stapes, oval window, external ear canal, and auricle. Rarely, the facial nerve may be hypoplastic or totally absent. Two abnormal vessels occasionally may accompany the facial nerve in the Fallopian canal: a persistent stapedial artery and a persistent lateral capital vein.

Chorda Tympani Nerve↗
PubMed2006

Topical application of mitomycin C to the middle ear is ototoxic in the gerbil.

HYPOTHESIS: Mitomycin C is ototoxic when applied topically to the structures of the middle ear. BACKGROUND: Mitomycin C is a topically applied medication widely used in a variety of surgical procedures to prevent excessive scar tissue formation. Its safety for use during otologic procedures has not been fully evaluated. METHODS: A laboratory study was undertaken using the Mongolian gerbil as an animal model. Both acute and chronic effects on cochlear function of mitomycin C were assessed with measurements of compound action potential (CAP) thresholds of the auditory nerve, CAP input/output functions, distortion product otoacoustic emissions, and endocochlear potentials. Morphologic changes were assessed with light microscopy using hematoxylin-eosin staining as well as transmission electron microscopy. RESULTS: Five-minute applications of mitomycin C (0.5 mg/ml) to the entire surface of the middle ear adversely affected CAP thresholds, input/output functions, distortion product otoacoustic emissions, and the endocochlear potential. Ninety-minute exposures of mitomycin C solely to the round window produced similar changes. Histologic evaluation of animals 1 week after treatment showed damage to cochlear hair cells, the stria vascularis, and spiral ganglion neurons when compared with controls. CONCLUSION: Mitomycin C can produce substantial sensorineural hearing loss when applied topically to the gerbil middle ear for even brief periods. Consequently, its safety for topical use in the human middle ear is highly questionable.

Action Potentials↗
PubMed2006

Pharmacodynamics of adenovector distribution within the inner ear tissues of the mouse.

Recent studies have demonstrated that delivery of genes to the inner ear can achieve a variety of effects ranging from support of auditory neuron survival to protection and restoration of hair cells, demonstrating the utility of vector based gene delivery. Translation of these findings to useful experimental systems or even clinical applications requires a detailed understanding of the pharmacokinetics of gene delivery in the inner ear. Ideal gene delivery systems will employ a well tolerated vector which efficiently transduces the appropriate target cells within a tissue, but spare non-target structures. Adenovectors based on serotype 5 (Ad 5) are commonly used vectors, are easy to construct and have a long track record of efficacious gene transfer in the inner ear. In this study we demonstrate that distribution of Ad5 vector occurs in a basal to apical gradient with rapid distribution of vector to the vestibule after delivery via a round window cochleostomy. Transduction of the vector and expression of the delivered transgene occurs by 10 min post vector delivery. At 24 h post delivery only 16% of vector that was initially detectable within the inner ear by quantitative PCR remained. Perilymph sampling was used to determine that vector concentrations in perilymph peaked at 30 min post delivery and then declined rapidly. Understanding these basic distribution patterns and parameters for delivery are important for the design of gene delivery vectors and vital for modeling dose responses to achieve safe efficacious delivery of a therapeutic agent.

Adenoviridae↗
PubMed1995

Natural killer cell response in the inner ear.

Heterologous tumor cells (human chronic myelogenous leukemia K-562 cells) were injected into the perilymph and skin in guinea pigs in order to study the induction of NK cell activity in the inner ear. An in vitro transmission electron microscopic and immunohistochemical study showed that K-562 cells were attacked by guinea pig large granular lymphocytes. K-562 cells injected through the round window membrane were found to be targeted by NK cells emerging from surrounding venules after 7 to 9 days. During this time morhological changes occurred in the organ of Corti and stria vacularis. These findings suggest that the inner ear response to foreign cells induces activation and invasion of NK cells which occur relatively late compared with those in other organs such as skin.

Animals↗
PubMedDate not supplied

Sudden hearing loss with delayed onset following head trauma.

Eight cases are reported with an identical history: head trauma with immediate profound deafness and vestibular dysfunction in one ear; then after a long latency, sudden hearing loss in the second ear, recurring and fluctuating with vestibular symptoms. Two cases were surgically explored. In one case 15 years after the trauma a perilymph fistula of the round window was found. In the other case a broad fracture of the basal coil of the cochlea was demonstrated, which had been asymptomatic for 18 years. In a retrospective study, 6 more cases with an identical course could be found. Latency between trauma and onset of symptoms in the second ear ranged from 4 to 33 years. Therapeutic and medico-legal aspects are discussed.

Adult↗
PubMed2006

[The clinical application of spiral CT virtual endoscopy of middle ear].

OBJECTIVE: To explore the clinical application of CT virtual endoscopy (CTVE) of ossicular chain in middle ear, and to establish the accurate method of observing ossicular chain and middle ear anatomy. METHOD: Volume scanning with spiral CT unit was performed in forty normal cases without illness of ear. Endoscopic 3D processing was carried out on a separate workstation equipped with a flying through program. From three isolated points(A, B and C), ear drum and ossicles were observed with CTVE method. The status of auditory ossicles connection were focused. RESULT: In CTVE via A, B and C points, the indication rates of the malleus, the indus, the drum cape, the canalis facialis horizontal section, and the prominence of horizontal semicircular canals were prosperously 100%. The indication rates of round window and the fenestra ovalis were 90%, 93%, 98% via A, B and C points respectively. And the indication rates of complete demonstration of ear ossicles were 100%, 95%, 93%, respectively. CONCLUSION: With appropriate approach, CTVE has advantage of showing ear ossicles and their connections, which is a good supplement of routine CT.

Adolescent↗