Spiral Ganglion Cells Research Articles

Age-related expression of plasma membrane Ca(2+) -ATPase isoform 2 in the cochleas of C57BL/6J mice

To investigate the location and distribution of plasma membrane Ca²⁺ -ATPase isoform 2(PMCA2) in the cochleas of C57BL/6J mice at various ages (4w, 14w, 22w, 45w), and to reveal the relationship of PMCA2 and age-related hearing loss (AHL). The distribution of PMCA2 in the cochleas of C57BL/6J mice was detected by immunohistochemistry at various ages (4w, 14w, 22w, 45w). Real-time polymerase chain reaction (Rt-PCR) was used to detect the level of PMCA2 mRNA in the cochleas of C57BL/6J mice at the ages of 4, 14, 22 and 45 weeks old respectively. Using SPSS17.0 software for statistical analysis. PMCA2 was mainly located in the hear cells, stria vascularis, and spiral ganglion cells. Faint labeling of PMCA2 was also observed in spiral ligament. Hair cells missed and the number of spiral ganglion cells reduced with age. Expression of PMCA2 in the cochleas of C57BL/6J mice also showed age-related decreasing. The results of Rt-PCR demonstrated the expression of mRNA of gene (Atp2b2) at 14 weeks age was significantly less than 4 week-old mice cochlears (P<0.05). The expression of mRNA of gene (Atp2b2) at 22 weeks age was significantly less than 14 week-old mice cochlears (P<0.05). The expression of mRNA of gene (Atp2b2) at 45 weeks age was significantly less than 14 week-old mice cochlears (P<0.01). PMCA2 is mainly located in the hear cells, stria vascularis, and spiral ganglion cells. Faint labeling of PMCA2 is also observed in spiral ligament. The expression of PMCA2 demonstrates an age-related decrease with age. The mRNA expression level of PMCA2 gene(Atp2b2) in the cochleas of C57BL/6J mice displayed an age-related decrease. PMCA2 transporters may play a critical role in maintaining the normal morphology of the inner ear and it may be related to AHL.

Enhanced bioavailability of nerve growth factor with phytantriol lipid-based crystalline nanoparticles in cochlea.

PurposeSupplementation of exogenous nerve growth factor (NGF) into the cochlea of deafened animals rescues spiral ganglion cells from degeneration. However, a safe and potent delivery of therapeutic proteins, such as NGF, to spiral ganglion cells remains one of the greatest challenges. This study presents the development of self-assembled cubic lipid-based crystalline nanoparticles to enhance inner ear bioavailability of bioactive NGF via a round window membrane route.MethodsA novel nanocarrier-entrapped NGF was developed based on phytantriol by a liquid precursor dilution, with Pluronic® F127 and propylene glycol as the surfactant and solubilizer, respectively. Upon dilution of the liquid lipid precursors, monodispersed submicron-sized particles with a slight negative charge formed spontaneously.ResultsBiological activity of entrapped NGF was assessed using pheochromocytoma cells with NGF-loaded reservoirs to induce significant neuronal outgrowth, similar to that seen in free NGF-treated controls. Finally, a 3.28-fold increase in inner ear bioavailability was observed after administration of phytantriol lipid-based crystalline nanoparticles as compared to free drug, contributing to an enhanced drug permeability of the round window membrane.ConclusionData presented here demonstrate the potential of lipid-based crystalline nanoparticles to improve the outcomes of patients bearing cochlear implants.

Gentamicin alters Akt-expression and its activation in the guinea pig cochlea

Gentamicin treatment induces hair cell death or survival in the inner ear. Besides the well-known toxic effects, the phosphatidylinositol-3 kinase/Akt (PI3K/Akt) pathway was found to be involved in cell protection. After gentamicin application, the spatiotemporal expression patterns of Akt and its activated form (p-Akt) were determined in male guinea pigs. A single dose of 0.1mL gentamicin (4mg/ear/animal) was intratympanically injected. The auditory brainstem responses (ABRs) were recorded prior to application and 1, 2 and 7days afterward. At these three time points the cochleae (n=10 in each case) were removed, transferred to fixative and embedded in paraffin. Seven ears were used as untreated controls. Gentamicin, Akt and p-Akt were identified immunohistochemically in various regions of the cochlea and their staining intensities were quantified on sections using digital image analysis. The application of gentamicin resulted in hearing loss with a concomitant up-regulation of Akt-expression in the organ of Corti and spiral ganglion cells and an additional activation in spiral ganglion cells. At the level of individual ears, clear intracellular correlations were found between Akt- and p-Akt-expression in the stria vascularis and interdental cells and, to a minor extent, in the spiral ligament and the organ of Corti. Furthermore, statistical evidence for the connection between gentamicin up-take and hearing loss was detected. The increase in Akt- and p-Akt-expression in the organ of Corti and spiral ganglion cells indicates a selected response of the cochlea against gentamicin toxicity.

Localization of sirtuins (SIRT1-7) in the aged mouse inner ear

Conclusion: The expression of sirtuin in vestibular end organs and cochlea responds differently to age-related changes. Down-regulation of SIRT1, 3, and 5 in the cochlea may weaken the protective activity regarding degeneration of the organ of Corti as well as of spiral ganglion cells, resulting in the development of age-related hearing loss. An increase in SIRT 1, 4, or 5 in vestibular tissue could indicate an increased need of detoxification of reactive oxygen species and an increased anti-ageing potential. Objective: To analyse the expression of sirtuins (SIRT1-7) in the normal young and old mouse inner ears. Methods: Young (8 weeks) and old (22 months) CBA/J mice were used in this study. Localization of SIRT1-7 in the inner ear, i.e. cochlea, vestibular end organs, and vestibular ganglion, was investigated using real-time PCR and immunohistochemistry. Results: In the vestibular end organs, the expression of SIRT1, 2, 4, 5 (both mRNA and protein), SIRT6, and 7 (only mRNA) was found to be increased, while a slightly decreased immunoreactivity was observed in SIRT3. In the cochlea, the expression of SIRT1, 3, and 5 (both mRNA and protein) was decreased in the old mice, whereas no noticeable difference was observed regarding SIRT2, 4, 6, or 7.

Hair Cell Loss, Spiral Ganglion Degeneration, and Progressive Sensorineural Hearing Loss in Mice with Targeted Deletion of Slc44a2/Ctl2.

SLC44A2 (solute carrier 44a2), also known as CTL2 (choline transporter-like protein 2), is expressed in many supporting cell types in the cochlea and is implicated in hair cell survival and antibody-induced hearing loss. In mice with the mixed C57BL/6-129 background, homozygous deletion of Slc44a2 exons 3–10 (Slc44a2Δ/Δ) resulted in high-frequency hearing loss and hair cell death. To reduce effects associated with age-related hearing loss (ARHL) in these strains, mice carrying the Slc44a2Δ allele were backcrossed to the ARHL-resistant FVB/NJ strain and evaluated after backcross seven (N7) (99 % FVB). Slc44a2Δ/Δ mice produced abnormally spliced Slc44a2 transcripts that contain a frameshift and premature stop codons. Neither full-length SLC44A2 nor a putative truncated protein could be detected in Slc44a2Δ/Δ mice, suggesting a likely null allele. Auditory brain stem responses (ABRs) of mice carrying the Slc44a2Δ allele on an FVB/NJ genetic background were tested longitudinally between the ages of 2 and 10 months. By 6 months of age, Slc44a2Δ/Δ mice exhibited hearing loss at 32 kHz, but at 12 and 24 kHz had sound thresholds similar to those of wild-type Slc44a2+/+ and heterozygous +/Slc44a2Δ mice. After 6 months of age, Slc44a2Δ/Δ mutants exhibited progressive hearing loss at all frequencies and +/Slc44a2Δ mice exhibited moderate threshold elevations at high frequency. Histologic evaluation of Slc44a2Δ/Δ mice revealed extensive hair cell and spiral ganglion cell loss, especially in the basal turn of the cochlea. We conclude that Slc44a2 function is required for long-term hair cell survival and maintenance of hearing.

Changes in the immunohistochemical localization of the glycine receptor in the superior olivary complex of adult circling mice.

Circling mice is a mutant model of spontaneous deafness exhibiting degenerated spiral ganglion cells in the cochlea and loss of organ of Corti. The balance between glycinergic inhibition and glutamatergic excitation in the lateral superior olive (LSO) is essential for the detection of inte-raural level differences. Long term weakening of glycinergic synaptic inhibition in the LSO may lead to the downregulation of synaptic release of glycine in dorsal cochlear nucleus and downregulation of postsynaptic glycine receptor (GlyR) activity in the LSO, which may contribute to hearing loss. The present study utilized an immunohistochemical method to assess changes in GlyR immunoreactivity (IR) and the cell number in the superior olivary complex (SOC) of heterozygote (+/cir) and homozygote (cir/cir) circling mice. A significant decrease in the IR was observed in all nuclei of the SOC of homozygous mice. Loss of GlyR immunoreactive cells and a decrement in cell size was also observed in the homozygotes. A decrease in the GlyR IR in the neurons and neuropils, cell number and size of the cir/cir, may lead to profound changes in inhibitory transmission and the functional properties in the SOC nuclei. Therefore, the functional loss of inhibitory neurotransmitters in the brainstem may result in deafness of adult cir/cir mice.

Cochlear changes in serous labyrinthitis associated with silent otitis media: A human temporal bone study

PurposeTo determine histopathological findings in the cochlea of human temporal bones with serous labyrinthitis. Materials and methodsWe compared human temporal bones with serous labyrinthitis (20 cases) associated with silent otitis media and without serous labyrinthitis (20 cases) to study location of serous labyrinthitis, the degree of endolymphatic hydrops, number of spiral ganglion cells and hair cells, loss of fibrocytes in the spiral ligament, and areas of the spiral ligament and stria vascularis. ResultsThe serous labyrinthitis caused significant loss of outer hair cells in the lower basal (P=0.006), upper basal (P=0.005), and lower middle (P=0.011) cochlear turns, and significant increase in the degree of endolymphatic hydrops than the control group (P=0.036). No significant difference was found in the loss of inner hair cells, in the number of spiral ganglion cells and fibrocytes in the spiral ligament, and in areas of the stria vascularis and spiral ligament (P>0.05). ConclusionsSerous labyrinthitis resulted in significant loss of outer hair cells and significant increase in the degree of endolymphatic hydrops.

Pulsed 980nm short wavelength infrared neural stimulation in cochlea and laser parameter effects on auditory response characteristics.

BackgroundAuditory neural stimulation with pulsed infrared radiation has been proposed as an alternative method to activate the auditory nerves in vivo. Infrared wavelengths from 1800–2150 nm with high water absorption were mainly selected in previous studies. However, few researchers have used the short-wavelength infrared (SWIR) for auditory nerve stimulation and limited pulse parameters variability has been investigated so far.MethodsIn this paper, we pioneered to use the 980 nm SWIR laser with adjustable pulse parameter as a stimulus to act on the deafened guinea pigs’ cochlea in vivo. Pulsed laser light was guided through the cochlear round window to irradiate the spiral ganglion cells via a 105 μm optical fiber, and then the laser pulse parameters variability and its influence to auditory response characteristics were studied.ResultsThe results showed that the optically evoked auditory brainstem response (OABR) had a similar waveform to the acoustically induced ABR with click sound stimulus. And the evoked OABR amplitude had a positive correlation, while the OABR latency period showed a negative correlation, with the laser pulse energy increase. However, when holding the laser peak power constant, the pulse width variability ranged from 100 to 800 μs showed little influence on the evoked OABR amplitude and its latency period.ConclusionsOur study suggests that 980 nm SWIR laser is an effective stimulus for auditory neurons activation in vivo. The evoked OABR amplitude and latency are highly affected by the laser pulse energy, while not sensitive to the pulse width variability in 100–800 μs range.

Effects of acute hypoxia on potassium channels in spiral ganglion cells of SD rats

The present study was to investigate the effects of acute hypoxia on the electrophysiological properties and outward current of spiral ganglion cell (SGC). SGC of newborn's Sprague Dawley (SD) rats were isolated and digested, primary cultured neurons for 8 h. By perfusion with physical saline solution containing no glucose and low oxygen, SGNs model of acute hypoxia was established. The whole-cell patch clamp recording was used to clarify the effect of hypoxia on the outward currents of SGC. The outward current of SGC showed characteristics of outward rectification, which contained two major components, one sensitive to the big conductance Ca²⁺-activated K⁺ channels (BKCa) which blocked by TEA, and the other could be suppressed by the KV channel blocker 4-AP. When holding at -60 mV, acute hypoxia increased the outward current of SGC in a voltage-dependent manner, which mainly increased the amplitude of the current activated by the votage ranged from 0 mV to +60 mV, and increased the amplitude of outward current from (1 160.0 ± 129.1) pA to (2 428 ± 239.3) pA (n = 9, P < 0.01) at holding potential of -60mV. By perfusion with the Potassium channel blocker TEA or 4-AP, the former could significantly reduced the increasing of outward currents induced by hypoxia on the SGC, the latter had no significant effect on the outward current increased by the hypoxia. These results suggest that acute hypoxia causes neuron hyperpolarization possibly by activating big conductance BKCa of the SGC. When the BKca channels are activated, K⁺ effluxes increase, which induces cell membrane hyperpolarization, and decreases cell excitability, which may affect the conducting function of SGC.

Empirical Derivation of Correction Factors for Human Spiral Ganglion Cell Nucleus and Nucleolus Count Units.

Profile count method for estimating cell number in sectioned tissue applies a correction factor for double count (resulting from transection during sectioning) of count units selected to represent the cell. For human spiral ganglion cell counts, we attempted to address apparent confusion between published correction factors for nucleus and nucleolus count units that are identical despite the role of count unit diameter in a commonly used correction factor formula. We examined a portion of human cochlea to empirically derive correction factors for the 2 count units, using 3-dimensional reconstruction software to identify double counts. The Neurotology and House Histological Temporal Bone Laboratory at University of California at Los Angeles. Using a fully sectioned and stained human temporal bone, we identified and generated digital images of sections of the modiolar region of the lower first turn of cochlea, identified count units with a light microscope, labeled them on corresponding digital sections, and used 3-dimensional reconstruction software to identify double-counted count units. For 25 consecutive sections, we determined that double-count correction factors for nucleus count unit (0.91) and nucleolus count unit (0.92) matched the published factors. We discovered that nuclei and, therefore, spiral ganglion cells were undercounted by 6.3% when using nucleolus count units. We determined that correction factors for count units must include an element for undercounting spiral ganglion cells as well as the double-count element. We recommend a correction factor of 0.91 for the nucleus count unit and 0.98 for the nucleolus count unit when using 20-µm sections.

Temporary Neurotrophin Treatment Prevents Deafness-Induced Auditory Nerve Degeneration and Preserves Function.

After substantial loss of cochlear hair cells, exogenous neurotrophins prevent degeneration of the auditory nerve. Because cochlear implantation, the current therapy for profound sensorineural hearing loss, depends on a functional nerve, application of neurotrophins is being investigated. We addressed two questions important for fundamental insight into the effects of exogenous neurotrophins on a degenerating neural system, and for translation to the clinic. First, does temporary treatment with brain-derived neurotrophic factor (BDNF) prevent nerve degeneration on the long term? Second, how does a BDNF-treated nerve respond to electrical stimulation? Deafened guinea pigs received a cochlear implant, and their cochleas were infused with BDNF for 4 weeks. Up to 8 weeks after treatment, their cochleas were analyzed histologically. Electrically evoked compound action potentials (eCAPs) were recorded using stimulation paradigms that are informative of neural survival. Spiral ganglion cell (SGC) degeneration was prevented during BDNF treatment, resulting in 1.9 times more SGCs than in deafened untreated cochleas. Importantly, SGC survival was almost complete 8 weeks after treatment cessation, when 2.6 times more SGCs were observed. In four eCAP characteristics (three involving alteration of the interphase gap of the biphasic current pulse and one involving pulse trains), we found large and statistically significant differences between normal-hearing and deaf controls. Importantly, for BDNF-treated animals, these eCAP characteristics were near normal, suggesting healthy responsiveness of BDNF-treated SGCs. In conclusion, clinically practicable short-term neurotrophin treatment is sufficient for long-term survival of SGCs, and it can restore or preserve SGC function well beyond the treatment period. Significance statement: Successful restoration of hearing in deaf subjects by means of a cochlear implant requires a healthy spiral ganglion cell population. Deafness-induced degeneration of these cells can be averted with neurotrophic factors. In the present study in deafened guinea pigs, we investigated the long-term effects of temporary (i.e., clinically practicable) treatment with brain-derived neurotrophic factor (BDNF). We show that, after treatment cessation, the neuroprotective effect remains for at least 8 weeks. Moreover, for the first time, it is shown that the electrical responsiveness of BDNF-treated spiral ganglion cells is preserved during this period as well. These findings demonstrate that treatment of the auditory nerve with neurotrophic factors may be relevant for cochlear implant users.

Soybean β-Conglycinin Prevents Age-Related Hearing Impairment.

Obesity-related complications are associated with the development of age-related hearing impairment. β-Conglycinin (β-CG), one of the main storage proteins in soy, offers multiple health benefits, including anti-obesity and anti-atherosclerotic effects. Here, to elucidate the potential therapeutic application of β-CG, we investigated the effect of β-CG on age-related hearing impairment. Male wild-type mice (age 6 months) were randomly divided into β-CG-fed and control groups. Six months later, the body weight was significantly lower in β-CG-fed mice than in the controls. Consumption of β-CG rescued the hearing impairment observed in control mice. Cochlear blood flow also increased in β-CG-fed mice, as did the expression of eNOS in the stria vascularis (SV), which protects vasculature. β-CG consumption also ameliorated oxidative status as assessed by 4-HNE staining. In the SV, lipofuscin granules of marginal cells and vacuolar degeneration of microvascular pericytes were decreased in β-CG-fed mice, as shown by transmission electron microscopy. β-CG consumption prevented loss of spiral ganglion cells and reduced the frequencies of lipofuscin granules, nuclear invaginations, and myelin vacuolation. Our observations indicate that β-CG ameliorates age-related hearing impairment by preserving cochlear blood flow and suppressing oxidative stress.

Neuronal erythropoietin overexpression protects mice against age-related hearing loss (presbycusis)

So far, typical causes of presbycusis such as degeneration of hair cells and/or primary auditory (spiral ganglion) neurons cannot be treated. Because erythropoietin's (Epo) neuroprotective potential has been shown previously, we determined hearing thresholds of juvenile and aged mice overexpressing Epo in neuronal tissues. Behavioral audiometry revealed in contrast to 5 months of age, that 11-month-old Epo-transgenic mice had up to 35 dB lower hearing thresholds between 1.4 and 32 kHz, and at the highest frequencies (50–80 kHz), thresholds could be obtained in aged Epo-transgenic only but not anymore in old C57BL6 control mice. Click-evoked auditory brainstem response showed similar results. Numbers of spiral ganglion neurons in aged C57BL6 but not Epo-transgenic mice were dramatically reduced mainly in the basal turn, the location of high frequencies. In addition, there was a tendency to better preservation of inner and outer hair cells in Epo-transgenic mice. Hence, Epo's known neuroprotective action effectively suppresses the loss of spiral ganglion cells and probably also hair cells and, thus, development of presbycusis in mice.

Spiral ganglion cells and macrophages initiate neuro-inflammation and scarring following cochlear implantation.

Conservation of a patient's residual hearing and prevention of fibrous tissue/new bone formation around an electrode array are some of the major challenges in cochlear implant (CI) surgery. Although it is well-known that fibrotic tissue formation around the electrode array can interfere with hearing performance in implanted patients, and that associated intracochlear inflammation can initiate loss of residual hearing, little is known about the molecular and cellular mechanisms that promote this response in the cochlea. In vitro studies in neonatal rats and in vivo studies in adult mice were performed to gain insight into the pro-inflammatory, proliferative, and remodeling phases of pathological wound healing that occur in the cochlea following an electrode analog insertion. Resident Schwann cells (SC), macrophages, and fibroblasts had a prominent role in the inflammatory process in the cochlea. Leukocytes were recruited to the cochlea following insertion of a nylon filament in adult mice, where contributed to the inflammatory response. The reparative stages in wound healing are characterized by persistent neuro-inflammation of spiral ganglion neurons (SGN) and expression of regenerative monocytes/macrophages in the cochlea. Accordingly, genes involved in extracellular matrix (ECM) deposition and remodeling were up-regulated in implanted cochleae. Maturation of scar tissue occurs in the remodeling phase of wound healing in the cochlea. Similar to other damaged peripheral nerves, M2 macrophages and de-differentiated SC were observed in damaged cochleae and may play a role in cell survival and axonal regeneration. In conclusion, the insertion of an electrode analog into the cochlea is associated with robust early and chronic inflammatory responses characterized by recruitment of leukocytes and expression of pro-inflammatory cytokines that promote intracochlear fibrosis and loss of the auditory hair cells (HC) and SGN important for hearing after CI surgery.

The paracrine effect of mesenchymal human stem cells restored hearing in β-tubulin induced autoimmune sensorineural hearing loss

The aim of this study was to examine the activities of hASCs (Human Adipose tissue Derived Stem Cells) on experimental autoimmune hearing loss (EAHL) and how human stem cells regenerated mouse cochlea cells. We have restored hearing in 19 years old white female with autoimmune hearing loss with autologous adipose tissue derived stem cells and we wish to understand the mechanism of restoration of hearing in animal model. BALB/c mice underwent to develop EAHL; mice with EAHL were given hASCs intraperitoneally once a week for 6 consecutive weeks. ABR were examined over time. The helper type 1 autoreactive responses and T-reg cells were examined. H&E staining or immunostaining with APC conjugated anti-HLA-ABC antibody were conducted. The organ of Corti, stria vascularis, spira ligament and spiral ganglion in stem cell group are normal. In control group, without receiving stem cells, the organ of Corti is replaced by a single layer of cells, atrophy of stria vascularis. Systemic infusion of hASCs significantly improved hearing function and protected hair cells in established EAHL. The hASCs decreased the proliferation of antigen specific Th1/Th17 cells and induced the production of anti-inflammatory cytokine interleukin10 in splenocytes. They also induced the generation of antigen specific CD4+CD25+Foxp3+T-reg cells. The experiment showed the restoration is due to the paracrine activities of human stem cells, since there are newly regenerated mice spiral ganglion cells, not human mesenchymal stem cells derived tissue given by intraperitoneally.This article is part of a Special Issue entitled <IEB Kyoto>.

Transactivation of human osteoprotegerin promoter by GATA-3.

Osteoprotegerin (OPG) is a key regulator of bone remodeling. Mutations in OPG are involved in a variety of human diseases. We have shown that cochlear spiral ganglion cells secrete OPG at high levels and lack of OPG causes sensorineural hearing loss in addition to the previously described conductive hearing loss. In order to study the regulation of OPG expression, we conducted a database search on regulatory elements in the promoter region of the OPG gene, and identified two potential GATA-3 binding sites. Using luciferase assays and site directed mutagenesis, we demonstrate that these two elements are GATA-3 responsive and support GATA-3 transactivation in human HEK and HeLa cells. The expression of wild type GATA-3 activated OPG mRNA and protein expression, while the expression of a dominant negative mutant of GATA-3 or a GATA-3 shRNA construct reduced OPG mRNA and protein levels. GATA-3 deficient cells generated by expressing a GATA-3 shRNA construct were sensitive to apoptosis induced by etoposide and TNF-α. This apoptotic effect could be partly prevented by the co-treatment with exogenous OPG. Our results suggest new approaches to rescue diseases due to GATA-3 deficiency – such as in hypoparathyroidism, sensorineural deafness, and renal (HDR) syndrome – by OPG therapy.

Noise induced reversible changes of cochlear ribbon synapses contribute to temporary hearing loss in mice

Conclusion: Noise exposure can cause a decline in cochlear ribbon synapses and result in consequent hearing loss. The reduction of synaptic puncta appears reversible and may contribute to hearing restoration in mice after noise exposure. Objective: To detect whether noise induced reversible changes of cochlear ribbon synapses contribute to temporary hearing loss in C57BL/6J mice. Methods: The mice were assigned randomly to five groups and exposed to white noise at 110 dB SPL for 2 h except the control group. ABR thresholds were acquired before noise exposure (control), immediately following exposure (Day 0), or on Days 4, 7, or 14 after noise exposure. Light microscopy, scanning emission microscopy, and whole mounts examination was utilized to study whether there is morphology change of outer hair cells (OHC), inner hair cells (IHC), or spiral ganglion cells (SGN) due to the 110 dB white noise. Moreover, experimental approaches, including immunostaining and confocal microcopy, were used to detect whether ribbon synapses were the primary targets of noise-induced temporary hearing loss. Result: Exposure to 110 dB white noise for 2 h induced TTS in mice, with the maximal ABR threshold elevations seen on the 4th day after noise exposure. There were no significant morphological changes in the cochlea. Paralleled changes of pre-synaptic ribbons in both the number and post-synaptic density (PSDs) during this noise exposure were detected. The number of pre-synaptic ribbon, post-synaptic density (PSDs), and co-localized puncta correlated with the shifts of ABR thresholds. Moreover, a complete recovery of ABR thresholds and synaptic puncta was seen on the 14th day after the noise stimulations.

Short-term Peripheral Auditory Effects of Cranial Irradiation: A Mouse Model.

Assess postcranial irradiation: (1) short-term threshold shift, (2) short-term peripheral auditory histopathology, and (3) the mouse as an experimental model. Adult mice were exposed to single-dose radiation of 10 to 60 Gy. Pre- and post-irradiation (baseline, 2-8 days) audiometric brainstem response data were recorded with analysis of cochlear ultrastructure. Significant threshold shift occurred at all test frequencies in mice exposed to ≥20 Gy at 4 to 6 days post-irradiation. Ultrastructurally in Rosenthal's canal and the spiral lamina, neuronal density and extracellular matrix decreased dramatically. There was overall preservation of hair cells, stria vascularis, and vasculature. No difference within Gy group was noted in the frequency or severity of pathology along the length of the cochlea. The initial impact of radiation in the first week post-exposure focuses on spiral ganglion cell bodies and peripheral projections, resulting in significant threshold shift for irradiation dosages≥20 Gy. This study demonstrates that the mouse is a viable model for study of short-term peripheral auditory effects using single-dose cranial irradiation. Additionally, with access to a precise animal irradiator, the mouse may be used as an experimental model for a fractionated irradiation dosage of 10 Gy, simulating stereotactic therapeutic cranial irradiation.

Integration of Pulse Trains in Humans and Guinea Pigs with Cochlear Implants.

Temporal integration (TI; threshold versus stimulus duration) functions and multipulse integration (MPI; threshold versus pulse rate) functions were measured behaviorally in guinea pigs and humans with cochlear implants. Thresholds decreased with stimulus duration at a fixed pulse rate and with pulse rate at a fixed stimulus duration. The rates of threshold decrease (slopes) of the TI and MPI functions were not statistically different between the guinea pig and human subject groups. A characteristic of the integration functions that the two groups shared was that the slopes of the TI functions were similar in magnitude to slopes of the MPI function only at low pulse rates (< approximately 300 pulses per second). This is consistent with the notion that the TI functions and the MPI functions at the low rates are mediated by a mechanism of long-term integration described in the statistical "multiple looks" model. Histological analysis of the guinea pig cochleae suggested that the slopes of both the MPI and the TI functions were dependent on sensory and neural health near the stimulated regions. The strongest predictor for spiral ganglion cell densities measured near the stimulation sites was the slope of the MPI functions below 1,000 pps. Several mechanisms may be considered to account for the association of shallow integration functions with poor sensory and neural status. These mechanisms are related to abnormal across-fiber synchronization, increased refractoriness and adaptation with impaired neural function, and steep growth of neural excitation with current level associated with neural pathology. The slope of the integration functions can potentially be used as a non-invasive measure for identifying stimulation sites with poor neural health and selecting those sites for removal or rehabilitation, but these applications remain to be tested.

Establishment of an experimental system to study the influence of electrical field on cochlear structures

Treatment of partial hearing loss with the combined electrical and acoustical stimulation (EAS) aims at restoring the hearing while preserving the residual hearing. The aim of present study was to establish an in vitro system to study the effects of an electrical field on the auditory hair cells and spiral ganglion cells. Cochlear tissues containing the organ of Corti, spiral limbus and spiral ganglion neurons were dissected from post-natal Wistar rats (p3–p5) and cultured in the micro-channels. Electric current was homogenously applied on the apical, medial and basal parts of explants. Biphasic rectangular pulses were applied continuously over a period of 30h or 42h and the explants were fixed and stained to visualize the hair cells and neurites. Application of electrical field for 30h has not induced significant changes in the number of inner or outer hair cells when compared to the control. However, after 42h of electric stimulation, the number of hair cells decreased significantly by about 30%. The medial and basal fragments were particularly affected. The number of neurites has not been influenced but significant neuritic beading, consistent with neurodegeneration, was observed after 42h of electric stimulation. Although performed with immature auditory tissues, our findings hint at the possibility of particular electric current inducing damage or loss of auditory hair cells, which should be considered when designing EAS electrodes.