Cochlear Pathology Research Articles

Vascular Supply of the Human Spiral Ganglion: Novel Three-Dimensional Analysis Using Synchrotron Phase-Contrast Imaging and Histology

Human spiral ganglion (HSG) cell bodies located in the bony cochlea depend on a rich vascular supply to maintain excitability. These neurons are targeted by cochlear implantation (CI) to treat deafness, and their viability is critical to ensure successful clinical outcomes. The blood supply of the HSG is difficult to study due to its helical structure and encasement in hard bone. The objective of this study was to present the first three-dimensional (3D) reconstruction and analysis of the HSG blood supply using synchrotron radiation phase-contrast imaging (SR-PCI) in combination with histological analyses of archival human cochlear sections. Twenty-six human temporal bones underwent SR-PCI. Data were processed using volume-rendering software, and a representative three-dimensional (3D) model was created to allow visualization of the vascular anatomy. Histologic analysis was used to verify the segmentations. Results revealed that the HSG is supplied by radial vascular twigs which are separate from the rest of the inner ear and encased in bone. Unlike with most organs, the arteries and veins in the human cochlea do not follow the same conduits. There is a dual venous outflow and a modiolar arterial supply. This organization may explain why the HSG may endure even in cases of advanced cochlear pathology.

Down-regulation of AMPK signaling pathway rescues hearing loss in TFB1 transgenic mice and delays age-related hearing loss.

AMP-activated protein kinase (AMPK) integrates the regulation of cell growth and metabolism. AMPK activation occurs in response to cellular energy decline and mitochondrial dysfunction triggered by reactive oxygen species (ROS). In aged Tg-mtTFB1 mice, a mitochondrial deafness mouse model, hearing loss is accompanied with cochlear pathology including reduced endocochlear potential (EP) and loss of spiral ganglion neurons (SGN), inner hair cell (IHC) synapses and outer hair cells (OHC). Accumulated ROS and increased apoptosis signaling were also detected in cochlear tissues, accompanied by activation of AMPK. To further explore the role of AMPK signaling in the auditory phenotype, we used genetically knocked out AMPKα1 as a rescue to Tg-mtTFB1 mice and observed: improved ABR wave I, EP and IHC function, normal SGNs, IHC synapses morphology and OHC survivals, with decreased ROS, reduced pro-apoptotic signaling (Bax) and increased anti-apoptotic signaling (Bcl-2) in the cochlear tissues, indicating that reduced AMPK attenuated apoptosis via ROS-AMPK-Bcl2 pathway in the cochlea. To conclude, AMPK hyperactivation causes accelerated presbycusis in Tg-mtTFB1 mice by redox imbalance and dysregulation of the apoptosis pathway. The effects of AMPK downregulation on pro-survival function and reduction of oxidative stress indicate AMPK serves as a target to rescue or relieve mitochondrial hearing loss.

Effects of Gsta4 deficiency on age-related cochlear pathology and hearing loss in mice.

The glutathione transferase (GST) detoxification system converts exogenous and endogenous toxins into a less toxic form by conjugating the toxic compound to reduced glutathione (GSH) by a variety of GST enzymes. Of the ~20 GST isoforms, GSTA4 exhibits high catalytic efficiency toward 4-hydroxynonenal (4-HNE), one of the most abundant end products of lipid peroxidation that contributes to neurodegenerative diseases and age-related disorders. Conjugation to GSH by GSTA4 is thought to be a major route of 4-HNE elimination. In the current study, we investigated the effects of Gsta4 deficiency on age-related cochlear pathology and hearing loss using young (3-5months old) and old (24-25months old) Gsta4+/+ and Gsta4-/- mice that were backcrossed onto the CBA/CaJ mouse strain, a well-established model of age-related hearing loss (AHL). At 3-5months of age, loss of Gsta4 resulted in decreased total GSTA activity toward 4-HNE in the inner ears of young mice. However, there were no differences in the levels of 4-HNE in the inner ears between Gsta4+/+ and Gsta4-/- mice at 3-5 or 24-25months of age. No histological abnormalities were observed in the cochlea and no hearing impairments were observed in young Gsta4-/- mice. At 24-25months of age, both Gsta4+/+ and Gsta4-/- mice showed elevated ABR thresholds compared to 3-month-old mice, but there were no differences in ABR thresholds, cochlear spiral ganglion neuron densities, or stria vascularis thickness between Gsta4+/+ and Gsta4-/- mice. Together, these results suggest that under normal physiological conditions or during normal aging, GSTA4 is not essential for removal of 4-HNE in mouse inner ears.

Otopathology in CHARGE syndrome.

Postmortem temporal bone computed tomography (CT) and histopathologic findings in an infant with CHARGE syndrome revealed bilateral cochleovestibular hypoplasia, including cochlear pathology relevant to cochlear implant candidacy. Both ears had absence of the superior semicircular canals (SCCs), severely hypoplastic posterior SCCs, and hypoplastic (right ear) or absent (left ear) lateral SCCs seen on CT and histopathology. Histopathology further revealed the absence of all SCC ampullae except the right lateral SCC ampulla and atrophic vestibular neuroepithelium in the saccule and utricle bilaterally. The right cochlea consisted of a basal turn with patent round window, and malformed middle turn (type IV cochlear hypoplasia), with a small internal auditory canal (IAC) but near normal cochlear nerve aperture (fossette). Quantification of spiral ganglion neurons (SGNs) on histologic sections revealed a reduced SGN population (35% of normal for age), but this ear would still have likely achieved benefit from a cochlear implant based on this population. The left cochlea consisted of only a basal turn with patent round window (type III cochlear hypoplasia) with a small IAC and very small cochlear nerve aperture. Notably, histology revealed that there were no SGNs in the cochlea, and therefore, this ear would not have been a good candidate for cochlear implantation. Level of evidence: IV.

Cochlear Surface Preparation in the Adult Mouse.

Auditory processing in the cochlea depends on the integrity of the mechanosensory hair cells. Over a lifetime, hearing loss can be acquired from numerous etiologies such as exposure to excessive noise, the use of ototoxic medications, bacterial or viral ear infections, head injuries, and the aging process. Loss of sensory hair cells is a common pathological feature of the varieties of acquired hearing loss. Additionally, the inner hair cell synapse can be damaged by mild insults. Therefore, surface preparations of cochlear epithelia, in combination with immunolabeling techniques and confocal imagery, are a very useful tool for the investigation of cochlear pathologies, including losses of ribbon synapses and sensory hair cells, changes in protein levels in hair cells and supporting cells, hair cell regeneration, and determination of report gene expression (i.e., GFP) for verification of successful transduction and identification of transduced cell types. The cochlea, a bony spiral-shaped structure in the inner ear, holds the auditory sensory end organ, the organ of Corti (OC). Sensory hair cells and surrounding supporting cells in the OC are contained in the cochlear duct and rest on the basilar membrane, organized in a tonotopic fashion with high-frequency detection occurring in the base and low-frequency in the apex. With the availability of molecular and genetic information and the ability to manipulate genes by knockout and knock-in techniques, mice have been widely used in biological research, including in hearing science. However, the adult mouse cochlea is miniscule, and the cochlear epithelium is encapsulated in a bony labyrinth, making microdissection difficult. Although dissection techniques have been developed and used in many laboratories, this modified microdissection method using cell and tissue adhesive is easier and more convenient. It can be used in all types of adult mouse cochleae following decalcification.

Dysfunction of the auditory system in sickle cell anaemia: a systematic review with meta-analysis.

To describe the occurrence of both peripheral and central auditory system dysfunction in sickle cell anaemia (SCA) patients and discuss the different mechanisms hypothesised to be responsible for these alterations. An electronic search was conducted using PubMed Central® (MEDLINE), LILACS® and Scopus® databases. This systematic review was performed in accordance with the PRISMA statement. Original observational studies that utilised audiological tests for auditory system evaluations in SCA were included. A total of 183 records were found in the databases searched. Twenty-one of these studies met the inclusion criteria. Pooled prevalence of sensorineural hearing loss (SNHL) was 20.5% (CI: 10.3-33%). Retrocochlear involvement was detected with the auditory brainstem response, which assesses integrity of the cochlea, 8th cranial nerve and brainstem structures. In addition, the increase in otoacoustic emission amplitudes in SCA patients indicates changes in cochlear micromechanics and precedes the expression of a detectable cochlear pathology. The prevalence of the SNHL is higher than in the general population. Dysfunction of the auditory system may be present in SCA patients, with the most probable mechanism being the presence of circulatory disturbances resulting from the chronic inflammatory state of the disease.

Hearing consequences in Gjb2 knock-in mice: implications for human p.V37I mutation.

Human p.V37I mutation of GJB2 gene was strongly correlated with late-onset progressive hearing loss, especially among East Asia populations. We generated a knock-in mouse model based on human p.V37I variant (c.109G>A) that recapitulated the human phenotype. Cochlear pathology revealed no significant hair cell loss, stria vascularis atrophy or spiral ganglion neuron loss, but a significant change in the length of gap junction plaques, which may have contributed to the observed mild endocochlear potential (EP) drop in homozygous mice lasting lifetime. The cochlear amplification in homozygous mice was compromised, but outer hair cells’ function remained unchanged, indicating that the reduced amplification was EP- rather than prestin-generated. In addition to ABR threshold elevation, ABR wave I latencies were also prolonged in aged homozygous animals. We found in homozygous IHCs a significant increase in ICa but no change in Ca2+ efficiency in triggering exocytosis. Environmental insults such as noise exposure, middle ear injection of KCl solution and systemic application of furosemide all exacerbated the pathological phenotype in homozygous mice. We conclude that this Gjb2 mutation-induced hearing loss results from 1) reduced cochlear amplifier caused by lowered EP, 2) IHCs excitotoxicity associated with potassium accumulation around hair cells, and 3) progression induced by environmental insults.

Vestibular testing in children with severe-to-profound hearing loss

Many studies showed that children with sensorineural hearing loss (SNHL) have possible vestibular affection which is related to the severity of cochlear pathology. Objectivesthis work is designed to evaluate vestibular function in children with congenital severe to profound SNHL and correlate the degree of hearing loss with the results of vestibular tests. Methods: this work included 52 children divided into two groups; control group consisted of 20 normal hearing children with no vestibular complaints, and study group consisted of 32 children with congenital severe to profound SNHL. All children were submitted to basic audiologic evaluation, combined vestibular evoked myogenic potentials, sinusoidal harmonic acceleration test (SHA) of rotatory chair test. Resultsall children in the control group had normal oVEMP and cVEMPs results while abnormal cVEMPs and oVEMPs results were found in 89% and 96.9% of the tested ears of the study group respectively. Sinusoidal harmonic acceleration test results were normal in control group with significant reduction in gain, phase lead and higher level of asymmetry in 50% of the children in study group. There was a significant relation between the degree of hearing loss and the cVEMPs, oVEMPs abnormalities, while SHA test results showed no such relationship. ConclusionThere is an evident vestibular abnormalities in children with severe to profound sensorineural hearing loss as revealed by the rotatory chair testing and VEMPs recordings. Vestibular assessment is very important in such group as it has an impact on their rehabilitation plan.

Advances and Challenges in Pharmaceutical Therapies to Prevent and Repair Cochlear Injuries From Noise.

Noise induces a broad spectrum of pathological injuries to the cochlea, reflecting both mechanical damage to the delicate architecture of the structures of the organ of Corti and metabolic damage within the organ of Corti and lateral wall tissues. Unlike ototoxic medications, the blood-labyrinth barrier does not offer protection against noise injury. The blood-labyrinth barrier is a target of noise injury, and can be weakened as part of the metabolic pathologies in the cochlea. However, it also offers a potential for therapeutic intervention with oto-protective compounds. Because the blood-labyrinth barrier is weakened by noise, penetration of blood-borne oto-protective compounds could be higher. However, systemic dosing for cochlear protection from noise offers other significant challenges. An alternative option to systemic dosing is local administration to the cochlea through the round window membrane using a variety of drug delivery techniques. The review will discuss noise-induced cochlear pathology, including alterations to the blood-labyrinth barrier, and then transition into discussing approaches for delivery of oto-protective compounds to reduce cochlear injury from noise.

Purinergic Signaling and Cochlear Injury-Targeting the Immune System?

Hearing impairment is the most common sensory deficit, affecting more than 400 million people worldwide. Sensorineural hearing losses currently lack any specific or efficient pharmacotherapy largely due to the insufficient knowledge of the pathomechanism. Purinergic signaling plays a substantial role in cochlear (patho)physiology. P2 (ionotropic P2X and the metabotropic P2Y) as well as adenosine receptors expressed on cochlear sensory and non-sensory cells are involved mostly in protective mechanisms of the cochlea. They are implicated in the sensitivity adjustment of the receptor cells by a K+ shunt and can attenuate the cochlear amplification by modifying cochlear micromechanics. Cochlear blood flow is also regulated by purines. Here, we propose to comprehend this field with the purine-immune interactions in the cochlea. The role of harmful immune mechanisms in sensorineural hearing losses has been emerging in the horizon of cochlear pathologies. In addition to decreasing hearing sensitivity and increasing cochlear blood supply, influencing the immune system can be the additional avenue for pharmacological targeting of purinergic signaling in the cochlea. Elucidating this complexity of purinergic effects on cochlear functions is necessary and it can result in development of new therapeutic approaches in hearing disabilities, especially in the noise-induced ones.

Early Indices of Reduced Cochlear Function in Young Adults with Type-1 Diabetes Revealed by DPOAE Fine Structure

The relationship between type-1 diabetes mellitus (DM) and cochlear dysfunction remains inconclusive. The purpose of this study was to examine otoacoustic emissions (OAEs) in normal-hearing young adults with type-1 DM as compared with matched controls and identify potential covariates influencing OAE findings. Cross-sectional study. N = 40 young adults aged 18-28 years including individuals with type-1 DM (n = 20) and age-gender matched controls (n = 20) with normal hearing sensitivity. Measures of pure-tone threshold sensitivity and OAEs, including distortion product otoacoustic emissions (DPOAEs), transient evoked OAEs, and DPOAE fine structure, were compared between groups. Covariates such as noise exposure and DM-related factors (e.g., duration of disease, glycated hemoglobin levels) were considered. Statistical analysis included analysis of variance and linear regression. Measures of hearing sensitivity and auditory function in both groups were comparable for all assays, except DPOAE fine structure. A reduced number of fine structure peaks and component amplitudes were found in the type-1 diabetes DM group with the primary difference in the reflection component. The results indicate that reduced cochlear function in young adults with type-1 DM can be revealed using DPOAE fine structure, suggesting potential clinical applications of DPOAE fine structure in early identification of cochlear pathology. Potential factors underlying these findings are discussed.

A Study of Aetiological Profile of Unilateral Sensorineural Hearing Loss

Introduction: It is necessary to identify the aetiology of sudden sensorineural hearing loss for proper management. Despite advancement in the field of diagnostic radiology, immunochemistry and genetic studies, there are still many cases of USNHL where a definite cause cannot be identified. In this study, an attempt has been made to identify the aetiological factors responsible for unilateral sensorineural hearing loss (USNHL).. 
 Materials and Methods: Seventyfive patients with acquired unilateral sensorineural hearing loss without chronic otitis media were included in the study. Hearing was assessed by tuning fork test and pure tone audiometry. Special tests were done to differentiate between cochlear and retrocochlear pathology, to objectively assess hearing loss and to diagnose nonorganic hearing loss. Radio-imaging was done to diagnose skull bone fractures, space occupying lesions in internal auditory meatus and cerebellopontine angle or intracranial pathologies. Biochemical analysis of blood, immunoglobulin and serological assay were done to rule out specific causes.
 Results: Majority of patients were within 21-30 years of age. 37 patients presented with sudden and remaining with progressive hearing loss. Majority (57.3%) were found to have idiopathic cochlear pathology. Amongst the remaining, there were 8 cases of acoustic trauma, 4 each of Meniere’s disease and cerebellopontine angle tumour and 3 each of Noise-induced hearing loss, labyrinthitis and Non-organic hearing loss. There were 2 cases of meningitis and 1 each of barotrauma, connective tissue disorder, iatrogenic trauma, fracture of petrous bone and cerebrovascular accident. 
 Conclusion: Most of the studies have been done on sudden sensorineural hearing loss. Current study, including sudden and progressive cases, is hence an attempt to ascertain aetiological profile of unilateral SNHL.

Effects of selective auditory-nerve damage on the behavioral audiogram and temporal integration in the budgerigar

Auditory-nerve fibers are lost steadily with age and as a possible consequence of noise-induced glutamate excitotoxicity. Auditory-nerve loss in the absence of other cochlear pathologies is thought to be undetectable with a pure-tone audiogram while degrading real-world speech perception (hidden hearing loss). Perceptual deficits remain unclear, however, due in part to the limited behavioral capacity of existing rodent models to discriminate complex sounds. The budgerigar is an avian vocal learner with human-like behavioral sensitivity to many simple and complex sounds and the capacity to mimic speech. Previous studies in this species show that intracochlear kainic-acid infusion reduces wave 1 of the auditory brainstem response by 40–70%, consistent with substantial excitotoxic auditory-nerve damage. The present study used operant-conditioning procedures in trained budgerigars to quantify kainic-acid effects on tone detection across frequency (0.25–8 kHz; the audiogram) and as a function of duration (20–160 ms; temporal integration). Tone thresholds in control animals were lowest from 1 to 4 kHz and decreased with increasing duration as in previous studies of the budgerigar. Behavioral results in kainic-acid-exposed animals were as sensitive as in controls, suggesting preservation of the audiogram and temporal integration despite auditory-nerve loss associated with up to 70% wave 1 reduction. Distortion-product otoacoustic emissions were also preserved in kainic-acid exposed animals, consistent with normal hair-cell function. These results highlight considerable perceptual resistance of tone-detection performance with selective auditory-nerve loss. Future behavioral studies in budgerigars with auditory-nerve damage can use complex speech-like stimuli to help clarify aspects of auditory perception impacted by this common cochlear pathology.

Coding-in-Noise Deficits are Not Seen in Responses to Amplitude Modulation in Subjects with cochlear Synaptopathy Induced by a Single Noise Exposure

Since the first report of noise-induced synaptic damage in animals without permanent threshold shifts (PTSs), the concept of noise-induced hidden hearing loss (NIHHL) has been proposed to cover the functional deficits in hearing associated with noise-induced synaptopathy. Moreover, the potential functional deficit associated with the noise-induced synaptopathy has been largely attributed to the loss of auditory nerve fibers (ANFs) with a low spontaneous spike rate (SSR). As this group of ANFs is critical for coding at suprathreshold levels and in noisy background, coding-in-noise deficit (CIND) has been considered to be main consequence of the synaptopathy. However, such deficits have not been verified after a single, brief exposure to noise without PTS. In the present study, synaptopathy was generated by such noise exposure in both mice and guinea pigs. Responses to amplitude modulation (AM) were recorded at a high sound level in combination with masking to evaluate the existence of CINDs that might be associated with loss of low-SSR ANFs. An overall reduction in response amplitude was seen in AM-evoked compound action potential (CAP). However, no such reduction was seen in the scalp-recorded envelope following response (EFR), suggesting a compensation due to increased central gain. Moreover, there was no significant difference in masking effect between the control and noise groups. The results suggest that either there is no significant CIND after the synaptopathy we created, or the AM response tested with our protocol was not sufficiently sensitive to detect such a deficit; far-field EFR is not sensitive to cochlear pathology.

Cochlear Capillary Pericytes.

Capillary pericytes in the cochlea of mammals are-compared to pericytes in other tissues, like the CNS-relatively poorly researched. To begin with, there is still a considerable debate as to whether the very last precapillary arterioles should-due to their contractile properties-may be considered to be pericytes.However, cochlear capillary pericytes have shifted into the center of attention in the past decade. Most mammals show a considerable number of pericytes in the stria vascularis of the cochlea-up to 1300 in a mouse alone. This high number may be explained by the observation that cochlear capillary pericytes may be differentiated into different subgroups, depending on the immune markers that are expressed by them. Corresponding with these subpopulations, cochlear pericytes fulfill three core functions in the physiology of the cochlea: Formation of the intrastrial blood-fluid barrier-Pericytes monitor the ion, fluid, and nutrient household and aid in the homeostasis thereof. Regulation of cochlear blood flow-By contraction on relaxation, pericytes contribute to the regulation of cochlear blood flow, a paramount function parameter of the cochlea. Immune response-Pericytes actually contribute to the immune response in inflammation of the cochlea. Due to these central roles in the physiology of the cochlea, pericytes actually play a major role in numerous cochlear pathologies, including, but not limited to, sudden sensorineural hearing loss, acoustic trauma, and inflammation of the cochlea.

A study on the outcome of various methods of administration of intratympanic dexamethasone in tinnitus of cochlear pathology

<p class="abstract"><strong>Background:</strong> The aim of the study was to compare the outcome of various methods of injecting intra tympanic steroids in patients with tinnitus of cochlear pathology.</p><p class="abstract"><strong>Methods:</strong> A prospective study was conducted on 56 patients with subjective tinnitus of cochlear pathology who were then divided into three groups. After thorough otological and audiological evaluation using standard questionnaire, ENT examination, pure tone audiometry, tone decay test, tinnitogram, CT scans of temporal bone and brain. Each patient underwent one of the three chosen methods of intra tympanic steroids administration randomly. The methods are 1-Tympanomeatal flap elevationand application of steroid soaked gelfoam sponge; 2-Transtympanic steroid injection; 3-Grommet insertion followed by steroid administration. These methods were performed for subjects with tinnitus of cochlear pathology from 2009 to 2011 at a neurotological clinic at Chennai. After following up on 1st, 3rd and 6 months the observations were statistically analysed. </p><p class="abstract"><strong>Results:</strong> Success rate for techniques viz tympanomeatal flap was 70%, transtympanic - 63%, grommet - 50%. But when comparing statistically all the three methods were equally successful.</p><p class="abstract"><strong>Conclusions:</strong> Intratympanic steroids for tinnitus (cochlear pathology) are a safe, simple and promising treatment option. Though all the methods of intra tympanic steroids injection had similar success rate, the tympanomeatal flap elevation method may be preferred since it can be done in a single sitting. However transtympanic injection remains the easiest and cost effective compared to the other two methods.</p>

Targeted PCR Array Analysis of Genes in Innate Immunity and Glucocorticoid Signaling Pathways in Mice Cochleae Following Acoustic Trauma

To comprehensively analyze cochlear gene expressions related to innate immunity and glucocorticoid signaling at onset of acute noise-induced hearing loss (NIHL). Recent studies suggested innate immunity is involved in the cochlear pathology of NIHL. Glucocorticoids may modulate immune actions in cochleae. Mice were exposed to 120 dB-octave band noise for 2 hours. Twelve hours later, a targeted PCR array analyzed cochlear expressions of 84 key genes in inflammation and immune pathways and 84 genes in the glucocorticoid signaling pathway. Real-time RT-PCR was used to analyze expression of two immune-related genes, Ccl12 and Glycam1, in noise-exposed cochleae with or without dexamethasone. In inflammatory and immune gene pathways, 31.0% (26/84 genes) were significantly upregulated (>2-fold change) or downregulated (<0.5-fold change) (p < 0.05) in noise-exposed cochleae compared with controls. Sixteen of these differentially expressed genes (DEGs) encoded chemokines. DEGs included Ccl12, Ccl2, Ccl4, Ccl7, Cxcl1, Cxcl10, and Ptgs2 (upregulated genes), and Ccr7, Cxcr2, Kng1, Ltb, and Tnfsf14 (downregulated genes). In the glucocorticoid signaling pathway, 92.9% (78/84 genes) were unchanged in noise-exposed cochleae without dexamethasone administration. Cochlear expressions of Ccl12 and Glycam1 were significantly upregulated by noise and downregulated by dexamethasone. The targeted PCR array demonstrated that several dozen genes involved in innate immunity are actively regulated in cochleae with NIHL. The glucocorticoid signaling pathway was not endogenously regulated at 12 hours post-noise trauma. Systemic dexamethasone downregulated Ccl12 and Glycam1, which are upregulated in noise-exposed cochleae. These data may provide a basis for genomic medicine treatment of acute sensorineural hearing loss.

Use of Proteomic Imaging Coupled With Transcriptomic Analysis to Identify Biomolecules Responsive to Cochlear Injury.

Exposure to noise or ototoxic agents can result in degeneration of cells in the sensory epithelium and auditory nerve, as well as non-sensory cells of the cochlear lateral wall. However, the molecular mechanisms underlying this pathology remain unclear. The purpose of this study was to localize and identify proteins in the cochlea that are responsive to noise or ototoxic exposure using a complementary proteo-transcriptomic approach. MALDI imaging of cochlear sections revealed numerous protein signals with distinct cochlear localization patterns in both cochlear injury models, of which six were chosen for further investigation. A query of proteomic databases identified 709 candidates corresponding to m/z values for the six proteins. An evaluation of mRNA expression data from our previous studies of these injured models indicated that 208 of the candidates were affected in both injury models. Downstream validation analyses yielded proteins with confirmatory distributions and responses to injury. The combined analysis of MALDI imaging with gene expression data provides a new strategy to identify molecular regulators responsive to cochlear injury. This study demonstrates the applicability of MALDI imaging for investigating protein localization and abundance in frozen sections from animals modeling cochlear pathology.

An evaluation of magnetic resonance imaging with histogram analysis in patients with idiopathic subjective tinnitus.

OBJECTIVE:Tinnitus is defined as the perception of sound in the ears without any acoustic stimulus. It has still not been determined whether tinnitus originates peripherally, centrally, or from several locations. The aim of the study was to determine any possible cochlear pathology in patients with normal hearing and tinnitus of unspecified etiology.METHODS:The study included 22 patients who presented at the clinic with the complaint of idiopathic subjective tinnitus that had been ongoing for at least 1 year. A total of 44 ears were included; 28 with tinnitus and 16 healthy ears. Unilateral tinnitus was determined in 16 patients and bilateral in six patients. The temporal magnetic resonance imaging (MRI) and audiogram results of the patients were retrieved from the hospital records. The MRI histogram measurement was made automatically and calculated for each ear separately.RESULTS:Entropy was found to be significantly higher in the control group and distribution was lower (p>0.01). In the tinnitus group, distribution was found to be broader, and kurtosis was statistically significantly greater (p<0.001).CONCLUSION:MRI histogram analysis can be considered as a method to be used in the clinical evaluation of the determination of possible cochlear pathology in ears with tinnitus.

Neural plasticity and its initiating conditions in tinnitus.

Deafferentation caused by cochlear pathology (which can be hidden from the audiogram) activates forms of neural plasticity in auditory pathways, generating tinnitus and its associated conditions including hyperacusis. This article discusses tinnitus mechanisms and suggests how these mechanisms may relate to those involved in normal auditory information processing. Research findings from animal models of tinnitus and from electromagnetic imaging of tinnitus patients are reviewed which pertain to the role of deafferentation and neural plasticity in tinnitus and hyperacusis. Auditory neurons compensate for deafferentation by increasing their input/output functions (gain) at multiple levels of the auditory system. Forms of homeostatic plasticity are believed to be responsible for this neural change, which increases the spontaneous and driven activity of neurons in central auditory structures in animals expressing behavioral evidence of tinnitus. Another tinnitus correlate, increased neural synchrony among the affected neurons, is forged by spike-timing-dependent neural plasticity in auditory pathways. Slow oscillations generated by bursting thalamic neurons verified in tinnitus animals appear to modulate neural plasticity in the cortex, integrating tinnitus neural activity with information in brain regions supporting memory, emotion, and consciousness which exhibit increased metabolic activity in tinnitus patients. The latter process may be induced by transient auditory events in normal processing but it persists in tinnitus, driven by phantom signals from the auditory pathway. Several tinnitus therapies attempt to suppress tinnitus through plasticity, but repeated sessions will likely be needed to prevent tinnitus activity from returning owing to deafferentation as its initiating condition.