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[Effect of a 6-week vitamin A-deficient diet on the sensory cells of the inner ear. Light and electron microscopic studies].

Histologic studies of the inner ear in rats with chronic vitamin A deficiency have produced contradicting results. In our own electronmicroscope investigations of the inner ear of young rats after a six week vitamin A deficit diet we found a lacking of the cuticle in the outer hair cells and a subtotally lacking of the cuticle in the inner hair cells. Furthermore, we found changes in the reticular system of the intermediate zone. These morphologic changes together with the recent findings of high concentrations of vitamin A in the corti organ support the hypothesis that the acoustic sensory receptors contain or functionally depend upon vitamin A.

Animals↗

[Use of the round window micro cath for inner ear therapy - results of a placebo-controlled, prospective study on chronic tinnitus].

BACKGROUND: The local therapy of inner ear diseases provides a means of directly applying pharmacological substances and delivering electrical stimulation to inner ear structures. Problems relating to dosage, systemic effects and the blood-cochlear barrier are thus avoided, which is not the case with systemic therapy. The preferred access point is the membrane of the round window. PATIENTS AND METHODS: An appropriately shaped catheter (DURECT Corporation, Cupertino, CA, USA), whose double-lumen passage system permits the variation of concentration and flow, is inserted into the round window niche. In a prospective, placebo-controlled clinical study, this application system was tested in 20 patients with chronic tinnitus. Following implantation the substances lidocaine, glutamate, glutamic acid and caroverine were applied via an attached external micropump. RESULTS: The values for tinnitus loudness, level of irritation caused by the tinnitus and subjective effectiveness of the therapy - measured by means of the visual analog scale (VAS) - showed no significant change, although the most marked improvement was indicated for caroverine. CONCLUSIONS: These results indicate that a positive effect was observable only in a proportion of the patients. Continuous therapy of tinnitus and inner ear diseases will only be possible once a totally implantable microdosage system has been developed.

Administration, Topical↗

Tolerance of membranous inner ear structures to pressure.

Pressure tolerance of round and oval labyrinthine windows and a cochlear segment represented by a part of the cochlear duct were investigated in experiments on cadaveric human temporal bones. The cochlear segment is less resistant than both the windows. Inner ear spaces are protected from pressure changes in the surroundings of the temporal bone by a system of narrow and comparatively long connections and some of them include also other structures strengthening the protective function (the valve described near the place where the cochlear aqueduct leads to scala tympani). Experiments with guinea pigs showed significance of inner ear integrity in protection from pressure changes. Tolerance of both windows was significantly higher in live animals than in cadaveric guinea pig bullae. Pressure tolerance of the windows was in turn higher in bullae than in isolated inner ear labyrinth. Conclusions were arrived at on the basis of the above facts that the inner ear is considerably resistant to pressure changes around it under normal circumstances. Ruptures in its parts appear only under special conditions and a number of factors participate in them. Window ruptures accompany most frequently injuries in other inner ear structures to which different degrees of hearing loss correspond. An isolated injury of windows is, from this viewpoint, rare even though it can be found and treated surgically best.

Animals↗

Effects of vasopressin on gene expression in rat inner ear.

Vasopressin regulates water excretion from the kidney by increasing water permeability of the collecting duct as a hormone secreted from the posterior pituitary. A clinical study reported that plasma levels of arginine vasopressin were significantly higher in patients suffering from Meniere's disease. It was histologically confirmed that chronic administration of vasopressin induced endolymphatic hydrops in guinea pigs. However, the mechanism of endolymphatic hydrops induced by vasopressin is still unclear. We use cDNA microarray to study the effects of vasopressin on gene expression profiles in rat inner ear to elucidate the possible mechanism of the induced hydrolabyrinth. Wistar rats were intraperitoneally injected with 50 microg/kg arginine vasopressin once a day for one week. Hydrolabyrinth in rat inner ear induced by administration of vasopressin was detected by HE stain. The bullae were dissected out for total RNA extraction. cDNAs were synthesized by reverse transcription and labeled with Cyanine3 (Cy3) or Cyanine5 (Cy5). The BiostarR-40s cDNA microarray was hybridized with the above cDNAs and the changes of mRNA expression intensity were showed by data analysis. Furthermore, the changes of aquaporins expression level were measured by reverse transcription polymerase chain (RT-PCR). Endolymphatic hydrops were present in rats intraperitoneally injected with vasopressin. 226 known differentially expressed genes were screened out in rat inner ear induced by vasopressin injection. Of the 226 genes, 18 transcripts were increased by 5-fold or more, and 7 transcripts were decreased to 0.2-fold or less. Ten differentially expressed genes were identified that associate with cell signal transduction, 14 differentially expressed genes were identified that relate to ion transport, 7 differentially expressed genes were involved in vesicle-mediated transport, and 2 differentially expressed genes were aquaporin 2 (AQP2) and aquaporin 7 (AQP7). The expression level of AQP2 was significantly higher and AQP7 was significantly lower. These results suggest that there are obvious differences in gene expression profiles in inner ear between vasopressin injected rats and normal control rats. Vasopressin may disturb fluid homeostasis in inner ear by way of signal transduction, ion transport, vesicle-mediated transport and aquaporins. It is likely that up-regulated expression of AQP2 mRNA and down-regulated expression of AQP7 mRNA in the rat inner ear caused by vasopressin induce an increased production and a decreased absorption of endolymph, resulting in endolymphatic hydrops.

Animals↗

Erythropoietin and erythropoietin receptor expression in the guinea pig inner ear.

The erythropoietin receptor (EPOR) is expressed in the brain and erythropoietin (EPO) has been shown to have neurotrophic and neuroprotective functions in the central nervous system and in the retina. These findings may be applied to the inner ear, pending EPO receptor presence. Accordingly, this study determines expression of EPO and EPOR in the inner ear of the guinea pig. Normal guinea pig inner ears were processed for immunohistochemistry, using poly-clonal antibodies against EPO and the EPO receptor. EPO expression was exclusively found in most, but not all spiral ganglion neurons. Expression of the EPO receptor was found in the cytoplasm of the inner and outer phalangeal cells (Deiters' cells), as well as the inner sulcus cells and the supporting cells of the organ of Corti (Hensen, Claudius and some Boettcher cells). Some spiral ganglion neurons or glial cells expressed the receptor, as did spiral ligament fibrocytes, some intermediate cells of stria vascularis and the endothelial cells of some modiolar vessels. No parts of the vestibular system stained positive for either antibody. We conclude, that EPO is expressed by spiral ganglion neurons and that the EPO receptor is widely expressed by several cell types within the guinea pig cochlea. We hypothesize on the existence of a local paracrine system and that EPO treatment may be feasible following inner ear damage.

Animals↗

Role of diffusible and transcription factors in inner ear development: implications in regeneration.

Organogenesis involves a dynamic balance of the mechanisms regulating cell division, differentiation and death. The development of the chicken embryo inner ear offers a well-characterised model at the morphological level to study which signals are implicated in the modulation of cellular activation and commitment. The early developmental decisions that control the origin of the inner ear elements are just beginning to be identified by complementary in vivo and in vitro studies. Insulin-like growth factor-I (IGF-I) and nerve growth factor (NGF) are among the best characterised diffusible factors acting during inner ear development. Although the cellular actions of these factors are beginning to be understood, the signalling pathways triggered by them still remain largely unknown. In this context, viral vehicles can be used to deliver genes and then analyse their functional roles during inner ear development. A model is proposed where the actions of IGF-I and NGF contribute to the combinatorial expression of Jun and Fos family members in particular domains of the otic vesicle. Some of these mechanisms may be also implicated in otic regeneration.

Animals↗

The effect of blood pressure on inner ear blood flow.

We investigated the effects of blood pressure on the blood flow in the inner ear as compared with other organs in normotensive rats (NR), spontaneously hypertensive rats (SHR) and renal hypertensive rats (RHR). The cardiac output and the regional blood flow were measured by a radioactive microsphere technique in conscious rats. The haemodynamics of the inner ear and other organs and the effects of a converting-enzyme inhibitor (SA-446) on the regional blood flow were compared among NR, SHR, and RHR, the blood pressure being 107, 152, and 185 mm Hg, respectively. With the exception of the heart, the organ blood flow was lower in SHR than in NR in all organs, including the inner ear. It was also lower in RHR than in SHR. The blood pressure dropped after i.v. injection of SA-446, while the regional blood flow increased. The effect was strongest in RHR, followed by SHR and finally NR.

Animals↗

Immunolocalization of aquaporin CHIP in the guinea pig inner ear.

Aquaporin CHIP (AQP-CHIP) is a water channel protein previously identified in red blood cells and water transporting epithelia. The inner ear is an organ of hearing and balance whose normal function depends critically on maintenance of fluid homeostasis. In this study, AQP-CHIP, or a close homologue, was found in specific cells of the inner ear, as assessed by immunocytochemistry with the use of affinity-purified polyclonal antibodies against AQP-CHIP.AQP-CHIP was predominantly found in fibrocytes in close association with bone, including most of the cells lining the bony labyrinth and in fibrocytes lining the endolymphatic duct and sac. AQP-CHIP-positive cells not directly apposing bone include cells under the basilar membrane, some type III fibrocytes of the spiral ligament, fibrocytes of the spiral limbus, and the trabecular perilymphatic tissue extending from the membranous to the bony labyrinth. AQP-CHIP was also found in the periosteum of the middle ear and cranial bones, as well as in chondrocytes of the oval window and stapes. The distribution of AQP-CHIP in the inner ear suggests that AQP-CHIP may have special significance for maintenance of bone and the basilar membrane, and for function of the spiral ligament.

Animals↗

Altered effect of arachidonic acid on inner ear blood flow in rats with streptozotocin-induced diabetes.

The present study was undertaken to clarify the altered effect of arachidonic acid on inner ear blood flow in rats with streptozotocin-induced diabetes by use of the laser-Doppler flowmeter. Drugs were administered intraarterially via the subclavian artery in a dose range that did not affect the systemic blood pressure. Both arachidonic acid and papaverine hydrochloride increased inner ear blood flow dose-dependently. Diabetic rats at 12 weeks, but not at 8 weeks, after the induction of diabetes showed a significant decrease in arachidonic acid response. However, there were no differences in papaverine response between diabetic and control rats. Pretreatment with ONO-3708, a selective thromboxane A2 antagonist, reversed the attenuated response to arachidonic acid found in diabetic rats. An increased response to thromboxane A2, which decreased inner ear blood flow, was also found in 12-week diabetic rats. In electrocochleograms, the latency in 12-week diabetic rats was significantly delayed compared with that in control rats, and this prolonged latency improved with insulin treatment. These results suggest that the responsiveness of inner ear blood flow to prostaglandins may be altered in individuals with diabetes mellitus.

Animals↗

Meshwork arrangement of mitochondria-rich, Na+,K+-ATPase-rich cells in the saccular epithelium of rainbow trout (Oncorhynchus mykiss) inner ear.

BACKGROUND: Electrolyte composition of the teleost fish inner ear endolymph is characterized by a high potassium concentration. From the ultrastructural characteristics, the mitochondria-rich cells (MRCs) in the inner ear epithelium are suggested to regulate the ionic composition of the endolymph. METHODS: In the present study, the ultrastructure of MRCs in the saccular epithelium of the rainbow trout (Onchorhynchus mykiss) was studied, and the immunocytochemical detection of Na+,K+-ATPase, the key enzyme of the ion-transport, in the saccular epithelium was conducted. Electrolyte composition of the saccular endolymph was also determined. RESULTS: Electron-microscopic observations revealed that MRCs located at the periphery of the sensory macula have numerous elongated mitochondria and a well-developed tubular system. Immunocytochemical detection of Na+,K+-ATPase on paraffin sections showed that immunoreactive (ir-) cells were distributed specifically around the sensory macula. Judging from their shape, size, and localization, the Na+,K+-ATPase ir-cells corresponded to the MRCs. The whole-mount immunocytochemistry using Na+,K+-ATPase as a marker for the MRC revealed that MRCs were connected with one another by extended cellular processes, and thus forming a dense meshwork structure around the macula. In the endolymph, potassium levels were 13 times higher than those in plasma, chloride levels were slightly higher whereas sodium, calcium, magnesium, and phosphate levels were lower. CONCLUSIONS: Thus, the saccular MRCs abundant in Na+,K+-ATPase are distributed around the sensory macula forming a dense meshwork structure, with the suggested function to regulate the electrolyte composition of the saccular endolymph.

Animals↗

Comparison of the inner ear ultrastructure between teleost fishes using different channels for communication.

The anatomy and ultrastructure of the inner ear of three species of gouramis which differ widely in acoustic behavior were studied using scanning electron microscopy. Of the three species. Trichopsis possess a pectoral sound-producing mechanism while Macropodus and Betta lack sonic organs. The general structure of the inner ear and the shapes of the sensory epithelia are very similar, although they do differ on the posterior part of the saccular macula which is more S-shaped in Trichopsis and Macropodus than in Betta. The maculae on the three species do not differ either in ciliary bundle type (cells with long kinocilia on the periphery of the maculae and cells with short kinocilia in the central region) or in hair cell orientation pattern. Quantitative measurements of hair cell densities and the size of the sensory epithelia of the saccule did not show significant differences between species. Data presented correlate with physiological results from other investigators showing similar auditory sensitivity in Trichopsis and Macropodus. The similarity in structure and function of the inner ears of gouramis on one hand, and the occurrence of sound-generating organs in just one genus, suggests that hearing evolved prior to vocalization and thus acoustic communication in this taxon.

Animal Communication↗

Cerebrospinal fluid otorrhea in a patient with congenital inner ear dysplasia.

A case of a 10-month-old boy with a cerebrospinal fluid (CSF) fistula in his right ear is reported. In the same ear, the patient also showed congenital inner ear dysplasia. The CSF fistula was obstructed surgically. Surgical exploration showed a fistula superior to the oval window and a normally shaped stapes. The stapes was removed and the fistula was closed by obliteration of the vestibulum with the temporal fascia and fat tissue. The location of the fistula was very rare; to our knowledge, this is the first reported case of CSF fistula superior to the oval window. The relationship between perilymphatic fistula and the microfissure revealed by temporal bone study is discussed.

Cerebrospinal Fluid Otorrhea↗

Comparison of ephrin-A ligand and EphA receptor distribution in the developing inner ear.

Members of the recently discovered Eph family appear to play important roles in a variety of developmental processes including tissue segmentation, cell migration and axonal guidance. To begin to understand the functions of the EphA subclass of receptors and their corresponding GPI-linked (ephrin-A) ligands in the inner ear, a developmental immunohistochemical analysis was completed. The results indicated that the ligands ephrin-A1 and ephrin-A2 were localized mainly at cellular boundaries in the inner ear. Ephrin-A1 was detected mainly in the epithelial cells lining the fluid filled ducts of the inner ear, whereas ephrin-A2 was prominently expressed in connective tissue regions. The receptor EphA4 was detected in vestibular hair cells. EphA5 and EphA7 were detected mainly in cochlear and vestibular supporting cells. These results suggest that these Eph molecules play a role in establishing the formation and cellular organization of the complex inner ear labyrinth. Additionally, all of the ligands and receptors evaluated were expressed in vestibular and cochlear neurons at various developmental stages, suggesting they may play a role in establishing or maintaining innervation to the inner ear.

Actins↗

Early effects of gentamicin on inner ear glycocalyx cytochemistry.

The early effects of gentamicin treatment on the inner ear glycocalyx were investigated using two cationic probes, colloidal thorium and cationized ferritin. Gentamicin treatment resulted in a diminished thorium reactivity of both the endolymphatic and perilymphatic glycocalyx of the hair cells after 1 day and complete abolishment of reactivity after 5 days. Cationized ferritin reactivity of the perilymphatic and endolymphatic glycocalyx was not significantly influenced. The cytochemistry of the inner ear glycocalyx and the possible biochemical changes induced by gentamicin are discussed.

Animals↗

Class III beta-tubulin expression in sensory and nonsensory regions of the developing avian inner ear.

A previous study showed that class III beta-tubulin, a widely used neuron-specific marker, is expressed in mature and regenerating hair cells but not the support cells of the avian inner ear. We investigated the expression of this marker in the developing avian inner ear. We found that class III beta-tubulin is not neuron-specific in the avian embryo, but appears to accumulate in neuronal cell types, including hair cells, about the time of their differentiation. In the developing inner ear, some degree of class III beta-tubulin immunoreactivity is found in all regions of the otic epithelium from its formation as the otic placode (stage 10 [embryonic day, E1.5]) until about stage 21 (E3.5), when the prospective tegmentum vasculosum begins to lose its staining. By stage 35 (E8-9), most of the nonsensory epithelia have lost their class III beta-tubulin staining, leaving distinct regions of staining between the morphological compartments of the inner ear. Concurrent with the loss of staining from nonsensory regions, the hair cells of the sensory epithelia accumulate class III beta-tubulin, whereas the supporting cells decrease their staining. We also observed a similar pattern of development in another hair cell organ, the paratympanic organ. Double labeling with the 275 kD hair cell antigen (HCA) indicated that the majority of hair cells identifiable with class III beta-tubulin are HCA-positive. Additionally, presumptive hair cells were identified which were not within defined sensory epithelia. Our findings show that class III beta-tubulin can be used as an early marker for hair cell differentiation in all hair cell sensory epithelia in the chicken.

Animals↗

[Effects of acute infrasound exposure on vestibular and auditory functions and the ultrastructural changes of inner ear in the guinea pig].

OBJECTIVE: To define the effects of acute infrasound exposure on vestibular and auditory functions and the ultrastructural changes of inner ear in guinea pigs. METHODS: The animals involved in the study were exposed to 8 Hz infrasound at 135dB SPL for 90 minutes in a reverberant chamber. The sinusoidal pendular test (SPT), auditory brainstem response (ABR) and distortion product otoacoustic emissions (DPOAE) were respectively detected pre-exposure and at 0(within 2 hrs), 2 and 5 day after exposure. The ultrastructures of the inner ear were observed by scanning electron microscopy. RESULTS: The slow-phase velocity and the frequency of the vestibular nystagmus elicited by sinusoidal pendular test (SPT) declined slightly following infrasound exposure, but the changes were not significant (P > 0.05). No differences in the ABR thresholds, the latencies and the interval peak latencies of I, III, V waves were found between the normal and the experimental groups, and among experimental groups. The amplitudes of DPOAE at any frequency declined remarkably in all experimental groups. The ultrastructures of the inner ear were damaged to different extent. CONCLUSION: Infrasound could transiently depress the excitability of the vestibular end-organs, decrease the function of OHC in the organ of Corti and cause damage to the inner ear of guinea pigs.

Animals↗

Inner ear degeneration in acoustic neurinoma.

The temporal bones of three cases of acoustic neurinoma are described to illustrate histopathological features of inner ear lesions due to chronic partial obstruction of blood circulation by the tumor in the internal auditory meatus. Degenerative changes in the inner ear due to acoustic neurinoma were evaluated and compared with changes in the opposite ear. The main pathological findings in the inner ear which were attributed to the tumor were degeneration of nerve fibers and of ganglion cells, degeneration of the stria vascularis, degeneration of the tectorial membrane, fibrosis and ossification of a semicircular canal. Fairly good preservation of sensory cells was observed in the presence of total degeneration of nerve fibers and ganglion cells and subtotal degeneration of the stria vascularis.

Aged↗

Drugs affecting the inner ear. A review of their clinical efficacy, mechanisms of action, toxicity, and place in therapy.

Many drugs have a site of action within the inner ear. The list includes therapeutic, diagnostic and ototoxic agents. Therapeutic agents are most useful in cases of infections, endolymphatic hydrops, vascular insufficiency, vertigo of peripheral origin, autoimmune disease, otosclerosis (otospongiosis), sudden hearing loss and tinnitus. For infections, the most widely used anti-microbial agents are the penicillins and cephalosporins. There are no antiviral agents that have been proven useful for inner ear viral infections. However, steroids have been of some value for controlling some of the sequelae. Steroids have also been useful in conjunction with ampicillin in cases of syphilitic hearing loss. In cases of endolymphatic hydrops, the diuretics chlorthalidone, hydrochlorothiazide and acetazolamide have been useful. When diuretic and diet therapy cannot control endolymphatic hydrops, ototoxic drugs such as streptomycin have been used. In cases of vascular insufficiency within the inner ear, vasodilators such as carbon dioxide, papaverine, buphenine (nylidrin), naftidrofuryl (nafronyl) and thymoxamine have been recommended, but their true efficacy is questionable. Some success with betahistine has been achieved but the mechanism of this drug's action may be other than vasodilatation. Vertigo is best controlled with antihistamines and anticholinergics and with certain calcium channel blockers. Autoimmune inner ear disease appears to respond to a combination of steroids and cyclophosphamide. Although controversial, current pharmacotherapy for otosclerosis includes sodium fluoride. Sudden hearing loss is treated with a 'shotgun' combination of drugs and/or bed rest. There are as yet no drugs which can be used to routinely reduce tinnitus although some medications may help the patient tolerate the problem. Lignocaine (lidocaine) is useful in diagnosing, and very evanescently reducing, tinnitus. Glycerin (glycerol) is useful in diagnosing endolymphatic hydrops and may at times transiently reduce tinnitus. The drugs most noted for their ototoxicity are the aminoglycoside antibiotics, certain diuretics, non-steroidal anti-inflammatory agents, certain anticancer agents and some miscellaneous chemicals. Some new research drugs are in clinical trials for tinnitus, hearing loss and vertigo, and the rational search for new otopharmacotherapeutic agents is increasing.

Ear, Inner↗