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Modification of atrial natriuretic peptide receptor expression in the rat inner ear.

HYPOTHESIS: The purpose of this animal study was to confirm the presence of all three atrial natriuretic peptide (ANP) receptor subtypes in the rat inner ear and compare the expression of each receptor after inner ear injection of ANP, phosphate-buffered saline, or a solution containing ANP incubated with anti-ANP antibody (to block upregulation). BACKGROUND: Receptors for ANP and related compounds have been localized in the inner ear of animals and humans. A previous study at this institution demonstrated the ability to up-regulate the expression of the three ANP receptors (ANP-A, ANP-B, ANP-C) in response to round window injection of ANP in the rat inner ear. METHODS: After surgical exposure, the round window of female Lewis rats was injected with various concentrations of ANP, ANP plus anti-ANP antibody, or control. Animals were killed 24 hours after injection, inner ear tissues were harvested and homogenized, and RNA was isolated for reverse-transcription polymerase chain reaction. RESULTS: Electrophoresis showed the presence of all three receptor subtypes with exposure to phosphate-buffered saline. Expression was significantly higher 24 hours after injection with the two concentrations of ANP. This increase was partially blocked with increasing relative concentrations of anti-ANP antibody. CONCLUSIONS: These findings confirm the presence and responsiveness of ANP receptors in the rat inner ear. The ability to block up-regulation with the antibody provides a potential new research tool for manipulating the function of this hormone system in experimental models and, ultimately, in understanding the mechanisms of fluid homeostasis in the inner ear.

Animals↗

Neural stem cells suppress the hearing threshold shift caused by cochlear ischemia.

Neural stem cells are multipotent progenitor cells that show self-renewal activity. In this study, we assessed the use of neural stem cells for ameliorating ischemia-reperfusion injury of the gerbil cochlea. Neural stem cells were injected into one inner ear through the round window 1 day after ischemic insult. Immunostaining for nestin showed that the distribution of neural stem cells was concentrated within the organ of Corti. Seven days after ischemia, the injury-induced auditory brainstem response threshold shift and progressive inner hair cell damage were markedly less on the neural stem cell-transplanted side. These results suggest that the transplantation of neural stem cells is therapeutically useful for preventing damage to hair cells that occurs after transient ischemia of the cochlea.

Animals↗

[Effects of buflomedil and naftidrofuryl on the human cochlear microcirculation measured by laser-Doppler].

The aim of this study was to assess the effects on cochlear blood flow measured by laser-Doppler of two vasoactive agents known for their supposed effectiveness in the presbyacousy treatment (buflomedil, naftidrofuryl), 16 patients undergoing acoustic neurinoma surgery were studied. Cochlear blood flow (CBF) was continuously recorded after the head of the probe was inserted into the internal ear through the round window. Systolic arterial pressure (SAP) and heart rate (HR) were continuously recorded via an arterial cannula. Hemodynamic variations due to buflomedil (400 mg in bolus) and to naftidrofuryl (200 mg in bolus) were compared with those of sodium nitroprusside (500 micrograms in bolus) in each case with anova. Buflomedil did not alter CBF (0%), SAP (+0.14 +/- 1.7%), HR (+3.4 +/- 3.4%). Naftidrofuryl provoked a significant decrease (P < 0.05) of CBF (-14.5 +/- 7.55%), SAP (-13.7 +/- 4%), and a significant increase (P < 0.05) of HR (+8.5 +/- 3.5%); there is a relationship between CBF and SAP (r = 0.88 P < 0.05). NPS provoked a significant decrease (P < 0.01) of CBF (-34.7 +/- 7.7%) SAP (-26.8 +/- 5.4%) and a significant increase (P < 0.01) of HR(+14.7 +/- 7.3%) in the same way of naftidrofuryl (P < 0.01). In conclusion, human cochlear microcirculation depends upon pharmacological hemodynamic variations such as animal models or middle ear microcirculation. If buflomedil did not alter it, naftidrofuryl provoked a reduction by a direct vasodilator effect inducing hypotension like sodium nitroprusside.

Cochlea↗

Streptomycin perfusion of the labyrinth through the round window plus intravenous streptomycin.

Streptomycin perfusion of the labyrinth through the round window membrane in the middle ear is a simple, safe, and effective way to stop the dizzy spells, fullness, and tinnitus of Ménière's disease without making the hearing worse. My results with 24 patients in the last 8 months are presented. Although the long-term effect of this operation remains to be seen, my experience with streptomycin perfusion of the labyrinth through the lateral semicircular canal leads me to believe these good results will be maintained in the future. Although the caloric response is not usually eliminated completely in the operated ear, it is reduced enough that the patient no longer has dizzy spells. Because the vestibular receptors are not completely destroyed, and the afferent and efferent nerves coming to and from them are undamaged, the patient compensates after this operation more quickly than when the vestibular receptors are completely destroyed by intramuscular or middle ear aminoglycoside, or when the afferent and efferent nerves of the vestibular receptors are cut as in labyrinthectomy or vestibular neurectomy. Hyaluronan is used to carry the streptomycin into the inner ear because it is known to penetrate the round window easily, and because being hygroscopic, it may reduce the amount of endolymph by osmosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Ear, Inner↗

Chemical and physical labyrinthectomy for Meniere's disease.

The use of intratympanic gentamicin is currently a popular and easily performed office procedure for the conservative treatment of the Meniere's disease patient who has failed medical therapy or who is not a candidate for surgical therapy. The procedure provides excellent control for the symptom of vertigo. Despite this success, there remains a significant risk of hearing loss irrespective of administered dose. In the future, antioxidant [42,43] or salicylate therapy may prevent aminoglycoside toxicity [44]. These prophylaxis methods have shown promise in the laboratory. Current methods do not allow for accurate drug delivery to the inner ear. Middle ear mucosal status, round window thickness or adhesion, patency of eustachian tube, and the effect of endolymphatic hydrops on ototoxicity are factors simply out of the control of the operator's hands. Judging by the number of recent articles, intratympanic gentamicin instillation will continue to be an area of interest for the otologist. Users should be encouraged to be consistent and conservative in gentamicin dosing. It is clear that vestibular ablation is not necessary for adequate control of vestibular symptoms and that larger doses may increase the risk of hearing loss. American Academy of Otolaryngology-Head and Neck Surgery guidelines [45] should be used and adhered to for reporting on the treatment of Meniere's disease, so that the literature may be more comparable. In the same light, a prospective standardized trial would be helpful in determining ultimate efficacy and risk to the patient. Transmastoid labyrinthectomy remains the surgical standard for extirpating the offending labyrinth when hearing preservation is not an issue. In appropriate patients, the procedure is a safe and effective method for relieving patients of vertiginous attacks. Most patients tolerate the procedure very well and are able to compensate fairly well over the course of several weeks to months.

Animals↗

[Indications for tympanotomy in "sudden deafness" and round window membrane rupture (author's transl)].

An operative exploration of the middle ear should be undertaken when deafness ins complete, when vestibular signs are present and when the patient asks for immediate medical care. The closure of the round window with soft tissue or fascia graft should be done within an few days after the event of "sudden deafness". We do not use an infusion therapy or blockade of ganglion stellatum in these cases and those of head trauma, because we saw no hearing gain after later operative intervention.

Audiometry, Pure-Tone↗

Acute Streptococcus pneumoniae meningogenic labyrinthitis. An experimental guinea pig model and literature review.

OBJECTIVE: To create an experimental model of Streptococcus pneumoniae type 3 meningogenic labyrinthitis (a leading cause of deafness) similar to that in human disease. DESIGN: Cohort analytic study of guinea pigs that were inoculated intrathecally with varying dilutions of S pneumoniae type 3; the progress of the disease was compared with that in saline solution-inoculated control animals. SUBJECTS: Healthy adult Hartley guinea pigs without clinical evidence of middle ear disease that were conveniently sampled. INTERVENTIONS: Intrathecal inoculation of 10(4) to 10(6) colony-forming units of S pneumoniae type 3 into 13 guinea pigs; signs and symptoms of meningitis/labyrinthitis were observed for 15 days and compared with those in two saline solution-inoculated control animals. MAIN OUTCOME MEASURES: Morbidity--labyrinthitis, meningitis; end point--death. RESULTS: The 10(4) to 10(6) colony-forming units of S pneumoniae type 3 caused inflammation that extended from the meninges to the inner ear via the cochlear aqueduct within 3 days after inoculation; a dose of 10(7) killed animals within 12 hours after inoculation. Three of five animals that were inoculated with a 10(6) dose died 3 days after inoculation; two of three animals that were inoculated with a 10(5) dose lived to 15 days after inoculation. One of two animals that were inoculated with a 10(4) dose did not become infected. Inflammation extended to the middle ear by round-window destruction. Reactive bone formation simulated labyrinthine osteosclerosis. Observers assessed histologic slides "blindly." CONCLUSION: Guinea pigs can survive 15 days after intrathecal inoculation of a 10(5) dose, with morphologic features similar to those in human disease. This is an effective model for this study of meningogenic labyrinthitis.

Acute Disease↗

Vestibular nerve and nuclei unit responses and eye movement responses to repetitive galvanic stimulation of the labyrinth in the rat.

Two-second cathodal current pulses were applied at one-minute intervals at a point external to the round window in the ear of each albino rat subject. Responses were recorded in the vestibular nerve ganglion, the vestibular nuclei (single units), or in the eye movements (search coil recording method) of anaesthetized, decerebrated, or alert rats. The unit responses to the galvanic stimuli were characterized and compared with responses to galvanic and rotational stimuli reported in the literature. The main focus of the study, however, was effects of stimulus repetition. In both the vestibular nerve and vestibular nuclei recordings, the responses of many units were substantially larger or smaller at the end of a 13-pulse stimulus train than at the beginning. In the vestibular nuclei, but not in the nerve, there was a slight bias towards a decrease in response magnitude, with 10/88 units showing decreases great enough to be considered as reflecting an habituation process. In contrast, the eye movement responses showed more consistent response decrements, especially in the alert condition, but also in the other conditions (none of the unit recordings were done in alert rats). It is concluded that some of the modifications underlying habituation of the vestibuloocular reflex probably occur in portions of the neuronal reflex pathways that are downstream from the vestibular nuclei.

Animals↗

Cochleotopic selectivity of a multichannel scala tympani electrode array using the 2-deoxyglucose technique.

The 2-deoxyglucose (2-DG) technique was used to study the cochleotopic selectivity of a multichannel scala tympani electrode array in four cats with another acting as an unstimulated control. Each animal was unilaterally deafened and a multichannel electrode array inserted 6 mm into the scala tympani. Thresholds to electrical stimulation were determined by recording electrically evoked auditory brainstem responses (EABRs). Each animal was injected with 2-DG, and electrically stimulated using bipolar electrodes located either distal or proximal to the round window. The contralateral ear was stimulated with acoustic tone pips at frequencies that matched the electrode place. Stimulation of both distal and proximal bipolar electrodes at 3 x EABR threshold, evoked localized 2-DG labelling in both ipsilateral cochlear nucleus (CN) and the contralateral inferior colliculus (IC), which was very similar in orientation and breadth to labelling evoked by the contralateral tone pips. The cochleotopic position of labelling to proximal stimulation was located in the 24-26 kHz region of each structure, whereas the distal labelling was located around 12 kHz. Distal stimulation at 10 x EABR threshold produced very broad 2-DG labelling in IC centered around the 12 kHz place. The present 2-DG results clearly illustrate cochleotopic selectivity using multichannel bipolar scala tympani electrodes. The extent of this selectivity is dependent on electrical stimulus levels. The 2-DG technique has great potential in evaluating the efficacy of new electrode array designs.

Acoustic Stimulation↗

Silverstein MicroWick.

Using the MicroWick to deliver otic medication to the inner ear fluids isa new, unique, effective, safe, efficient, and inexpensive method to treat inner ear disease. This self-treatment method using otic medication represents a major breakthrough in the treatment of inner ear disease. It allows the otologist to treat inner ear disease much as the ophthalmologist treats eye disease using eye drops. In the future, new drugs and medications will likely be developed that will relieve vertigo attacks, improve certain types of sensorineural hearing loss, and reduce tinnitus. The MicroWick will be available for patients to self-administer these medications to the inner ear through the round window membrane.

Administration, Topical↗

Acquired irreversible sensorineural hearing loss associated with otitis media with effusion.

The development of irreversible sensorineural hearing loss (SNHL) in three patients having chronic otitis media with effusion of the serous or mucoid type is described. Anamnestic, clinical, and laboratory investigations revealed no evidence of known etiologic factors, diseases, or conditions that could have induced inner ear damage. It seems that the pathogenetic mechanism of this complication of chronic otitis media with effusion is penetration of infectious agents or their toxic products from the middle ear to the inner ear through the round window membrane. The SNHL may be of different types and degrees, from a high-tone hearing loss to complete anacusis. The development of SNHL was not prevented or influenced by the insertion of tympanostomy tubes.

Adult↗

Discharge properties of pigeon single auditory nerve fibers after recovery from severe acoustic trauma.

The time course of recovery of compound action potential (CAP) thresholds was observed in individual adult pigeons after severe acoustic trauma. Each bird had electrodes implanted on the round window of both ears. One ear was exposed to a tone of 0.7 kHz at 136-142 dB SPL for 1 hr under general anesthesia. Recovery of CAP audiograms was monitored twice a week after trauma. Single unit recordings from auditory nerve fibers were made after 3 weeks and after 4 or more months of the exposure. The CAP was abolished immediately after overstimulation in all animals. Based on the temporal patterns of functional recovery of the CAP three groups of animals were identified. The first group was characterized by fast functional recovery starting immediately after trauma followed by a return to pre-exposure values within 3 weeks. In the second group, slow functional recovery of threshold started 1-2 weeks after trauma followed by a return to pre-exposure values by 4-5 weeks. A mean residual hearing loss of 26.3 dB at 2 kHz remained. The third group consisted of animals that did not recover after trauma. Three weeks after the exposure, tuning curves of single auditory nerve fibers were very broad and sometimes irregular in shape. Their thresholds hovered around 120 dB SPL. Spontaneous firing rate and driven rate were much reduced. Four or more months after exposure, the thresholds and sharpness of tuning of many single units were almost completely recovered. Spontaneous firing rate and driven rate were comparable to those of control animals. In the slow recovery group neuronal tuning properties showed less recovery, especially at frequencies above the exposure frequency. Thresholds and sharpness of tuning were normal at frequencies below the exposure frequency, but were much poorer at frequencies above the exposure. Spontaneous firing rate was much reduced in fibers with high characteristic frequencies. In fast recovering animals, the papilla was repopulated with hair cells after 4 months. In slow recovering animals, short (abneural) hair cells were still missing over large parts of the papilla after 4 months of recovery. Residual short (abneural) hair cell loss was largest at two areas, one more basal and the other more apical to the characteristic place of the traumatizing frequency. The results show that, in adult birds, functional recovery from severe damage to both short (abneural) and tall (neural) hair cells occurs. However, the onset of recovery is delayed and the time course is slower than after destruction of short (abneural) hair cells alone. Also, recovery is incomplete, both functionally and morphologically. There is residual permanent hearing loss, and regeneration of short (abneural) hair cells is incomplete.

Action Potentials↗

Tympanometry and fistula test.

The 'fistula test' is performed when an abnormal opening between the vestibule and the middle ear cavity is suspected. The fistula is usually seen after stapedectomy, but may also occur after trauma to a normal ear when the round window membrane may rupture. Tympanometry with an electronystagmographic (ENG) tracing may show a positive result after stapedectomy in the absence of a fistula, and there may conversely be a normal ENG tracing after tympanometry when there is in fact a perilymph fistula. The authors explain the reasons for this paradoxical response. In no way does it detract from the value of the test, which only needs to be interpreted correctly.

Acoustic Impedance Tests↗

[Protective and rescue effects of transgenic bFGF/GFP expression mediated by cationic liposome on gentamicin-induced guinea pig cochlear toxicity].

OBJECTIVE: To observe the expression of cationic stearylamine (SA) liposome mediated basic fibroblast growth factor/green fluorescence protein (bFGF/GFP) gene in the cochlea of guinea pig, and evaluate the protection and rescue action of bFGF against the damage caused by gentamicin. METHODS: Thirty-six guinea pigs were divided into 3 experimental groups. Prevention group with inoculation of SA-bFGF/GFP complexes through the round window of right ear and injection of gentamicin 150 mg.kg(-1).d(-1) one day after for 8 days and rescue group with injection of gentamicin for 8 days and infusion of SA-bFGF/GFP complexes in the same way on the ninth day, and control group with only injection of gentamicin for 8 days. Auditory brainstem responses (ABR) was measured prior to and after the administration and before the animals were killed respectively. The animals were killed after the experiment and ABR test, and specimens and slices of chochleae were made to examine the absence of outer and inner hair cells. The expression of GFP in cochlea shown by green fluorescence was observed with fluorescent microscopy. RESULTS: Fluorescent microscopy showed green fluorescence in the cochleae of guinea pigs in prevention and rescue groups. There was no significant difference in ABR threshold between the left and right ears of animals in each group before and after experiment, among both ears of animals in the 3 groups before experiment, and between prevention and rescue group groups before killing (all P > 0.05). However, the ABR thresholds in prevention group and rescue group were significantly lower than that in control group before the animals were killed (P < 0.01 and P < 0.05). The average number of lost outer hair cells was 5 106 +/- 299 cells and 5 605 +/- 109 cells in prevention group and rescue group respectively, without a significant difference between them (P > 0.05). The average amount of missing inner hair cells was 301 +/- 64 cells and 487 +/- 92 cells in prevention group and rescue group respectively, without a significant difference between them (P > 0.05), and significantly lower than that in control group (1 062 +/- 67, P < 0.01 and P < 0.05). The average amount of missing outer hair cells in control group was 6 248 +/- 119 cells, significantly higher than that in prevention group (5 106 +/- 299, P < 0.01) and that in rescue group (5 605 +/- 109, P < 0.05). CONCLUSION: SA-liposome mediated bFGF/GFP gene, which was perfused in one ear, can be expressed highly in both cochleae of the guinea pig, and may protect and rescue cochlea against gentamicin ototoxicity.

Amines↗

Evidence of a Common Pathway in Noise-Induced Hearing Loss and Carboplatin Ototoxicity.

In spite of the differences in the nature of the insult, the hearing loss from ototoxic drugs and noise exposure share a number of similarities in cochlear pathology. This paper explores the common factors between noise-induced hearing loss and ototoxicity by experimentally manipulating cochlear glutathione (GSH). In the first experiment, chinchillas were treated with a drop of saline (50 &mgr;l) on the round window of one ear and a drop of buthionine sulfoximine (BSO, 50 &mgr;l of 200 mM) on the other ear. BSO is a drug that blocks GSH synthesis and it was hypothesised that GSH-depressed ears would be more vulnerable to noise. Six hours after treatment, the animals were exposed to a 105 dB 4 kHz octave band noise for 4 hours, then a second dose of BSO was applied 2 hours later. The BSO treated ears showed more temporary threshold shifts and reduced GSH staining at day 4 post exposure, but there was no BSO effect in terms of greater permanent threshold shift (PTS) or hair cell loss. In the second experiment, chinchillas were pretreated with BSO and 3 days later were given either a single dose of carboplatin (25 mg/kg i.p.), a double dose (day 3 and 7) or only BSO. Chinchillas that received BSO and the double dose of carboplatin had significantly greater loss of inner and outer hair cells than the carboplatin chinchillas. In addition, the BSO and carboplatin chinchillas also had larger decreases in evoked response amplitudes suggesting that GSH depletion potentiated the ototoxicity of carboplatin. These results are discussed in terms of the role of reactive oxygen species in creating hearing loss and the potential protective role of glutathione.

Journal Article↗

Preoperative electrical stimulation for cochlear implant selection. The use of ear canal electrodes versus transtympanic electrodes.

Preoperative electrostimulation tests were performed on 43 postlingually deaf and 20 prelingually deaf cochlear implant (CI) candidates. The stimulating electrode was placed at three different locations, i.e. the round window, the promontory and the ear canal and the results were compared. The evoked sensations were reported to be of auditory origin by most of the postlingually deaf CI candidates. Prelingually deaf subjects could not always distinguish clearly and reliably between "hearing" and "feeling". The percentage of stimulated ears of postlingually deaf subjects in whom hearing sensations were evoked was almost identical for the three locations of the stimulating electrode. However, in 5 out of the 7 ears without hearing sensations during ear canal stimulation (ECS), hearing sensations could be evoked during either promontory stimulation (PS) or round window stimulation (RWS). The mean threshold level for "hearing" at a stimulation frequency of 62 Hz was lowest during RWS, 7.7 dB higher during PS and 35.8 dB higher during ECS. The mean electrical dynamic range at 62 Hz was most favourable during RWS (23.9 dB), smaller during PS (15.6 dB) and smallest during ECS (10.0 dB). All differences were statistically significant. Placement of the ear canal electrode was easier, less frightening for the patient and required less time than insertion of the needle electrode for PS or RWS. Therefore we recommend the use of ECS to examine whether the CI candidate can be stimulated, and of RWS if more detailed information is required.

Adolescent↗

Distribution of hyaluronan in the middle and inner ear. A light microscopical study in the rat using a hyaluronan-binding protein as a specific probe.

The histochemical distribution of hyaluronan (hyaluronic acid, HYA) was analyzed in middle and inner ear tissues from rats by use of microwave-aided fixation, a hyaluronan-binding protein and the avidin-biotin/peroxidase staining procedure. In the middle ear HYA was mainly localized in the pars flaccida, the ossicles, the round window membrane and in the endomysium of the middle ear muscles. The subepithelial stroma of the Eustachian tube was strongly HYA-positive. In the inner ear, the spiral ligament of the cochlea and the connective tissue surrounding the nerve fibers emerging from the crista ampullaris stained intensely for HYA. Except for a weak staining of the basilar membrane, the Corti organ was devoid of HYA. The heterogenous distribution of HYA may indicate its specific involvement in middle and inner ear physiology and pathology.

Animals↗