[The role of neurotropic therapy in the treatment of acute sensorineural impairment of hearing following a viral infection].

The objective of the study. To estimate the efficacy of consecutive prescription of combined neurotropic therapy in addition to conventional treatment modalities for the patients presenting with acute sensorineural impairment of hearing. The results of analysis of the examination and treatment of 58 patients presenting with acute sensorineural impairment of hearing following a viral infection are presented. The patients of the study group (group 1) received the treatment according to the following scheme: intramuscular injections of milgamma at a dose of 2 ml for 10 days followed by the intake of milgamma tablets thrice daily during 20 days. The control patients (group 2) was comprised of the patients given conventional therapy alone. The efficacy of the treatment was estimated based on the results of tonal threshold audiometry before and after the treatment. It was shown that neurotropic therapy can speed up the process of hearing recovery in the patients suffering its acute sensorineural impairment by at least 5 days. The efficacy of traditional treatment combined with milgamma therapy in the patients with acute sensorineural impairment of hearing of allegedly viral etiology proved to be higher than that of conventional therapy alone within the first days after the onset of the treatment.

beta-Bungarotoxin application to the round window: an in vivo deafferentation model of the inner ear.

Hearing impairment can be caused by a primary lesion to the spiral ganglion neurons (SGNs) with the hair cells kept intact, for example via tumours, trauma or auditory neuropathy. To mimic these conditions in animal models various methods of inflicting damage to the inner ear have been used. However, only a few methods have a selective effect on the SGNs, which is of importance since it might be clinically more relevant to study hearing impairment with the hair cells undamaged. beta-Bungarotoxin is a venom of the Taiwan banded krait, which in vitro has been shown to induce apoptosis in neurons, leaving remaining cochlear cells intact. We wanted to create an in vivo rat model of selective damage to primary auditory neurons. Under deep anaesthesia, 41 rats received beta-Bungarotoxin or saline to the round window niche. At postoperative intervals between days 3 and 21 auditory brainstem response (ABR) measurement, immunohistochemistry, SGN quantification and cochlear surface preparation were performed. The results in the beta-Bungarotoxin-treated ears, as compared with sham-operated ears, show significantly increased ABR thresholds at all postoperative intervals, illustrating a severe to profound hearing loss at all tested frequencies (3.5, 7, 16 and 28 kHz). Quantification of the SGNs showed no obvious reduction in neuronal numbers until 14 days postoperatively. Between days 14 and 21 a significant reduction in SGN numbers was observed. Cochlear surface preparation and immunohistochemistry showed that the hair cells were intact. Our results illustrate that in vivo application of beta-Bungarotoxin to the round window niche is a feasible way of deafening rats by SGN reduction while the hair cells are kept intact.

Molecular identity and functional properties of a novel T-type Ca2+ channel cloned from the sensory epithelia of the mouse inner ear.

The molecular identity of non-Cav1.3 channels in auditory and vestibular hair cells has remained obscure, yet the evidence in support of their roles to promote diverse Ca2+-dependent functions is indisputable. Recently, a transient Cav3.1 current that serves as a functional signature for the development and regeneration of hair cells has been identified in the chicken basilar papilla. The Cav3.1 current promotes spontaneous activity of the developing hair cell, which may be essential for synapse formation. Here, we have isolated and sequenced the full-length complementary DNA of a distinct isoform of Cav3.1 in the mouse inner ear. The channel is derived from alternative splicing of exon14, exon25A, exon34, and exon35. Functional expression of the channel in Xenopus oocytes yielded Ca2+ currents, which have a permeation phenotype consistent with T-type channels. However, unlike most multiion channels, the T-type channel does not exhibit the anomalous mole fraction effect, possibly reflecting comparable permeation properties of divalent cations. The Cav3.1 channel was expressed in sensory and nonsensory epithelia of the inner ear. Moreover, there are profound changes in the expression levels during development. The differential expression of the channel during development and the pharmacology of the inner ear Cav3.1 channel may have contributed to the difficulties associated with identification of the non-Cav1.3 currents.

Auditory physiology and anatomy of octavolateral efferent neurons in a teleost fish.

Vertebrate hair cell systems receive innervation from efferent neurons in the brain. Here we report the responses of octavolateral efferent neurons that innervate the inner ear and lateral lines in a teleost fish, Dormitator latifrons, to directional linear accelerations, and compare them with the afferent responses from the saccule, the main auditory organ in the inner ear of this species. Efferent neurons responded to acoustic stimuli, but had significantly different response properties than saccular afferents. The efferents produced uniform, omnidirectional responses with no phase-locking. Evoked spike rates increased monotonically with stimulus intensity. Efferents were more broadly tuned and responsive to lower frequencies than saccular afferents, and efferent modulation of the otolithic organs and lateral lines is likely more pronounced at lower frequencies. The efferents had wide dynamic ranges, shallow rate-level function slopes, and low maximum discharge rates. These findings support the role of the efferent innervation of the otolithic organs as part of a general arousal system that modulates overall sensitivity of the peripheral octavolateral organs. In addition, efferent feedback may help unmask biologically relevant directional stimuli, such as those emitted by a predator, prey, or conspecific, by reducing sensitivity of the auditory system to omnidirectional ambient noise.

Distinct roles for hindbrain and paraxial mesoderm in the induction and patterning of the inner ear revealed by a study of vitamin-A-deficient quail.

The hindbrain and cranial paraxial mesoderm have been implicated in the induction and patterning of the inner ear, but the precise role of the two tissues in these processes is still not clear. We have addressed these questions using the vitamin-A-deficient (VAD) quail model, in which VAD embryos lack the posterior half of the hindbrain that normally lies next to the inner ear. Using a battery of molecular markers, we show that the anlagen of the inner ear, the otic placode, is induced in VAD embryos in the absence of the posterior hindbrain. By performing grafting and ablation experiments in chick embryos, we also show that cranial paraxial mesoderm which normally lies beneath the presumptive otic placode is necessary for otic placode induction and that paraxial mesoderm from other locations cannot induce the otic placode. Two members of the fibroblast growth factor family, FGF3 and FGF19, continue to be expressed in this mesodermal population in VAD embryos, and these may be responsible for otic placode induction in the absence of the posterior hindbrain. Although the posterior hindbrain is not required for otic placode induction in VAD embryos, the subsequent patterning of the inner ear is severely disrupted. Several regional markers of the inner ear, such as Pax2, EphA4, SOHo1 and Wnt3a, are incorrectly expressed in VAD otocysts, and the sensory patches and vestibulo-acoustic ganglia are either greatly reduced or absent. Exogenous application of retinoic acid prior to 30 h of development is able rescue the VAD phenotype. By performing such rescue experiments before and after 30 h of development, we show that the inner ear defects of VAD embryos correlate with the absence of the posterior hindbrain. These results show that induction and patterning of the inner ear are governed by separate developmental processes that can be experimentally uncoupled from each other.

Serotonergic innervation of the inner ear: is it involved in the general physiological control of the auditory receptor?

The auditory pathway of mammals is composed of two complementary ascending afferent and descending efferent independent systems. The brainstem nuclei and cochlear projections for these systems are now well-known. In addition, a highly conspicuous distribution for serotonergic fibers was recently reported. This study focused on these serotonergic fibers and their neurons of origin. We identified several different types of serotonergic brainstem neurons surrounding the superior olivary complex and around the periolivary nuclei. Even though the 5-hydroxytryptamine (5-HT) efferent cochlear innervation originates in the periolivary area of the superior olivary complex system projecting to the cochlea, it is not involved in the transduction of pure tones during auditory processing. However, recent findings, after cochlear blockade of serotonin transporters, strongly suggested that this neuroactive substance has an important turnover within the auditory receptor. The presence of a conspicuous peripheral nerve distribution together with a particular brainstem origin could define a complex role for this innervation. Therefore, 5-HT fibers projecting to the cochlea might be involved, as in other parts of the auditory pathway, in alertness, attention, control of sleep or wakefulness cycles, and state of urgency prior to the transduction processing at the auditory receptor. A lack, or reduction, of the function of these fibers could result in pathological alterations.

[Autoradiography study of the uptake of 3H-2-deoxyglucose in the inner ear in normal and unilaterally sympathectomized albino rats]. / Autoradiographische Studie über den Einbau der 3H-2-Deoxyglukose im Innenohr bei normalen und einseitig sympathektomierten Albinoratten.

Using the autoradiographic technique for water-soluble substances, the uptake of 3H-2-deoxyglucose (2-DG) was measured in the inner ear tissue. The experiments were performed on 26 albino rats (22-27 days). 10 microCi/g b.w. of 2-DG were applied i.v. and the control group was immediately kept in the Camera silens in darkness. The main group was exposed to pink noise (50 Hz - 10 kHz of 60-110 dB). 8 unilaterally sympathectomised animals were exposed to pink noise of different intensity after 24h. The highest uptake of 2-DG independent of the intensity of noise was observed in the cochlear lateral wall (stria vasc., sp. lig., sp. prominentia) in the basal turn and decreased to the apical turn. The uptake in the lateral wall increased from 30-40 dB to 60dB and decreased from 60 to 80 dB exposure. The region of the inner hair cells was clearly marked by 80 dB. With increasing intensity of noise exposure, 2-DG uptake in the spiral ganglion increased continually. Unilateral sympathectomy did not result in any significant difference in the uptake of 2-DG. Therefore, the hypothesis that the decrease of 2-DG uptake in the lateral wall may be due to sympathico-adrenergic vasoconstriction is not verified by our results.

Vestibulo-thalamic projections studied with antidromic technique in the cat.

The vestibulo-thalamic projection was investigated in anaesthetized cats. Electrical stimulation of posterolateral thalamic areas frequently changed the spontaneous firing pattern of neurons in the vestibular nuclei but only 5% were antidromically invaded. This group was further analysed with regard to types of labyrinthine and somatosensory input; thalamo-projecting neurons in the vestibular nuclei are frequently located in the lateral vestibular nucleus, they receive no monosynaptic inflow from the labyrinth and they often receive convergent vestibular and somatosensory input.