-
Biochemical and Biophysical Research... May 2024Although research on hearing loss, including the identification of causative genes, has become increasingly active, the pathogenic mechanism of hearing loss remains...
Although research on hearing loss, including the identification of causative genes, has become increasingly active, the pathogenic mechanism of hearing loss remains unclear. One of the reasons for this is that the structure of the inner ear of mice, which is commonly used as a genetically modified animal model, is too small and complex, making it difficult to accurately capture abnormalities and dynamic changes in vivo. Especially, Reissner's membrane is a very important structure that separates the perilymph and endolymph of the inner ear. This malformation or damage induces abnormalities in hearing and balance. Until now, imaging analyses, such as magnetic resonance imaging (MRI) and computed tomography, are performed to investigate the inner ear structure in vivo; however, it has been difficult to analyze the small inner ear structure of mice owing to resolution. Therefore, there is an urgent need to develop an image analysis method that can accurately capture the structure of the inner ear of mice including Reissner's membrane, both dynamically and statically. This study aimed to investigate whether it is possible to accurately capture the structure (e.g., Reissner's membrane) and abnormalities of the inner ear of mice using an 11.7 T MRI. By combining two types of MRI methods, in vivo and ex vivo, we succeeded for the first time in capturing the fine structure of the normal mouse inner ear, such as the Reissner's membrane, and inflammatory lesions of otitis media mouse models in detail and accurately. In the future, we believe that understanding the state of Reissner's membrane during living conditions will greatly contribute to the development of research on inner ear issues, such as hearing loss.
PubMed: 38820624
DOI: 10.1016/j.bbrc.2024.150153 -
PloS One 2024Hearing loss is a pivotal risk factor for dementia. It has recently emerged that a disruption in the intercommunication between the cochlea and brain is a key process in...
Hearing loss is a pivotal risk factor for dementia. It has recently emerged that a disruption in the intercommunication between the cochlea and brain is a key process in the initiation and progression of this disease. However, whether the cochlear properties can be influenced by pathological signals associated with dementia remains unclear. In this study, using a mouse model of Alzheimer's disease (AD), we investigated the impacts of the AD-like amyloid β (Aβ) pathology in the brain on the cochlea. Despite little detectable change in the age-related shift of the hearing threshold, we observed quantitative and qualitative alterations in the protein profile in perilymph, an extracellular fluid that fills the path of sound waves in the cochlea. Our findings highlight the potential contribution of Aβ pathology in the brain to the disturbance of cochlear homeostasis.
Topics: Animals; Alzheimer Disease; Disease Models, Animal; Mice; Perilymph; Cochlea; Amyloid beta-Peptides; Mice, Transgenic; Hearing Loss
PubMed: 38728348
DOI: 10.1371/journal.pone.0303375 -
Magnetic Resonance in Medical Sciences... Apr 2024The endolymph of the inner ear, vital for balance and hearing, has long been considered impermeable to intravenously administered gadolinium-based contrast agents...
PURPOSE
The endolymph of the inner ear, vital for balance and hearing, has long been considered impermeable to intravenously administered gadolinium-based contrast agents (GBCAs) due to the tight blood-endolymph barrier. However, anecdotal observations suggested potential GBCA entry in delayed heavily T2-weighted 3D-real inversion recovery (IR) MRI scans. This study systematically investigated GBCA distribution in the endolymph using this 3D-real IR sequence.
METHODS
Forty-one patients suspected of endolymphatic hydrops (EHs) underwent pre-contrast, 4-h, and 24-h post-contrast 3D-real IR imaging. Signal intensity in cerebrospinal fluid (CSF), perilymph, and endolymph was measured and analyzed for temporal dynamics of GBCA uptake, correlations between compartments, and the influence of age and presence of EH.
RESULTS
Endolymph showed a delayed peak GBCA uptake at 24h, contrasting with peaks in perilymph and CSF at 4h. Weak to moderate positive correlations between endolymph and CSF contrast effect were observed at both 4 (r = 0.483) and 24h (r = 0.585), suggesting possible inter-compartmental interactions. Neither the presence of EH nor age significantly influenced endolymph enhancement. However, both perilymph and CSF contrast effects significantly correlated with age at both time points.
CONCLUSION
This study provides the first in vivo systematic confirmation of GBCA entering the endolymph following intravenous administration. Notably, endolymph uptake peaked at 24h, significantly later than perilymph and CSF. The lack of a link between endolymph contrast and both perilymph and age suggests distinct uptake mechanisms. These findings shed light on inner ear fluid dynamics and their potential implications in Ménière's disease and other inner ear disorders.
PubMed: 38569839
DOI: 10.2463/mrms.mp.2024-0011 -
Frontiers in Neurology 2024An idiopathic perilymphatic fistula (PLF) can be difficult to diagnose because patients present with sudden sensorineural hearing loss (SSHL) and/or vestibular symptoms...
OBJECTIVES
An idiopathic perilymphatic fistula (PLF) can be difficult to diagnose because patients present with sudden sensorineural hearing loss (SSHL) and/or vestibular symptoms without any preceding events. In such cases, we currently test for cochlin-tomoprotein (CTP) to confirm the diagnosis of idiopathic PLF because CTP is only detected in the perilymph. In this study, we report the clinical course of five patients definitively diagnosed with idiopathic PLF who underwent PLF repair surgery using transcanal endoscopic ear surgery (TEES).
PATIENTS AND METHODS
Five patients were initially treated with intratympanic dexamethasone for SSHL, at which time a CTP test was also performed (preoperative CTP test). Due to refractory hearing loss and/or fluctuating disequilibrium, PLF repair surgery using TEES was performed to seal the oval and round windows using connective tissue and fibrin glue. These patients were diagnosed with definite idiopathic PLF based on pre- or intra-operative CTP test results (negative, < 0.4 ng/mL; intermediate, 0.4-< 0.8 ng/mL; and positive, > 0.8 ng/mL). We evaluated pre- and intra-operative CTP values, intraoperative surgical findings via a magnified endoscopic view, and pre- and post-operative changes in averaged hearing level and vestibular symptoms.
RESULTS
Pre- and intra-operative CTP values were positive and intermediate in three patients, positive and negative in one patient, and negative and positive in one patient. None of the patients had intraoperative findings consistent with a fistula between the inner and middle ears or leakage of perilymph. Only two patients showed a slight postoperative recovery in hearing. Four patients complained of disequilibrium preoperatively, of whom two had resolution of disequilibrium postoperatively.
CONCLUSION
A positive CTP test confirms PLF in patients without obvious intraoperative findings. The CTP test is considered more sensitive than endoscopic fistula confirmation. We consider that CTP test results are important indicators to decide the surgical indication for idiopathic PLF repair surgery. In our experience with the five cases, two of them showed improvements in both hearing and vestibular symptoms.
PubMed: 38560729
DOI: 10.3389/fneur.2024.1376949 -
Otology & Neurotology Open Mar 2023Proteins enriched in the perilymph proteome of Meńier̀e disease (MD) patients may identify affected cell types. Utilizing single-cell transcriptome datasets from the...
HYPOTHESIS
Proteins enriched in the perilymph proteome of Meńier̀e disease (MD) patients may identify affected cell types. Utilizing single-cell transcriptome datasets from the mammalian cochlea, we hypothesize that these enriched perilymph proteins can be localized to specific cochlear cell types.
BACKGROUND
The limited understanding of human inner ear pathologies and their associated biomolecular variations hinder efforts to develop disease-specific diagnostics and therapeutics. Perilymph sampling and analysis is now enabling further characterization of the cochlear microenvironment. Recently, enriched inner ear protein expression has been demonstrated in patients with MD compared to patients with other inner ear diseases. Localizing expression of these proteins to cochlear cell types can further our knowledge of potential disease pathways and subsequent development of targeted therapeutics.
METHODS
We compiled previously published data regarding differential perilymph proteome profiles amongst patients with MD, otosclerosis, enlarged vestibular aqueduct, sudden hearing loss, and hearing loss of undefined etiology (controls). Enriched proteins in MD were cross-referenced against published single-cell/single-nucleus RNA-sequencing datasets to localize gene expression to specific cochlear cell types.
RESULTS
In silico analysis of single-cell transcriptomic datasets demonstrates enrichment of a unique group of perilymph proteins associated with MD in a variety of intracochlear cells, and some exogeneous hematologic and immune effector cells. This suggests that these cell types may play an important role in the pathology associated with late MD, suggesting potential future areas of investigation for MD pathophysiology and treatment.
CONCLUSIONS
Perilymph proteins enriched in MD are expressed by specific cochlear cell types based on in silico localization, potentially facilitating development of disease-specific diagnostic markers and therapeutics.
PubMed: 38516320
DOI: 10.1097/ONO.0000000000000027 -
Frontiers in Molecular Neuroscience 2024The blood-labyrinth-barrier (BLB) is a semipermeable boundary between the vasculature and three separate fluid spaces of the inner ear, the perilymph, the endolymph and... (Review)
Review
The blood-labyrinth-barrier (BLB) is a semipermeable boundary between the vasculature and three separate fluid spaces of the inner ear, the perilymph, the endolymph and the intrastrial space. An important component of the BLB is the blood-stria-barrier, which shepherds the passage of ions and metabolites from strial capillaries into the intrastrial space. Some investigators have reported increased "leakage" from these capillaries following certain experimental interventions, or in the presence of inflammation or genetic variants. This leakage is generally thought to be harmful to cochlear function, principally by lowering the endocochlear potential (EP). Here, we examine evidence for this dogma. We find that strial capillaries are not exclusive, and that the asserted detrimental influence of strial capillary leakage is often confounded by hair cell damage or intrinsic dysfunction of the stria. The vast majority of previous reports speculate about the influence of strial vascular barrier function on the EP without directly measuring the EP. We argue that strial capillary leakage is common across conditions and species, and does not significantly impact the EP or hearing thresholds, either on evidentiary or theoretical grounds. Instead, strial capillary endothelial cells and pericytes are dynamic and allow permeability of varying degrees in response to specific conditions. We present observations from mice and demonstrate that the mechanisms of strial capillary transport are heterogeneous and inconsistent among inbred strains.
PubMed: 38486963
DOI: 10.3389/fnmol.2024.1368058 -
Frontiers in Pharmacology 2024The inner ear is the organ responsible for hearing and balance. Inner ear dysfunction can be the result of infection, trauma, ototoxic drugs, genetic mutation or... (Review)
Review
The inner ear is the organ responsible for hearing and balance. Inner ear dysfunction can be the result of infection, trauma, ototoxic drugs, genetic mutation or predisposition. Often, like for Ménière disease, the cause is unknown. Due to the complex access to the inner ear as a fluid-filled cavity within the temporal bone of the skull, effective diagnosis of inner ear pathologies and targeted drug delivery pose significant challenges. Samples of inner ear fluids can only be collected during surgery because the available procedures damage the tiny and fragile structures of the inner ear. Concerning drug administration, the final dose, kinetics, and targets cannot be controlled. Overcoming these limitations is crucial for successful inner ear precision medicine. Recently, notable advancements in microneedle technologies offer the potential for safe sampling of inner ear fluids and local treatment. Ultrasharp microneedles can reach the inner ear fluids with minimal damage to the organ, collect μl amounts of perilymph, and deliver therapeutic agents . This review highlights the potential of ultrasharp microneedles, combined with nano vectors and gene therapy, to effectively treat inner ear diseases of different etiology on an individual basis. Though further research is necessary to translate these innovative approaches into clinical practice, these technologies may represent a true breakthrough in the clinical approach to inner ear diseases, ushering in a new era of personalized medicine.
PubMed: 38327988
DOI: 10.3389/fphar.2024.1328460 -
Journal of Otology Jan 2024Sudden sensorineural hearing loss (SSNHL) is a prevalent emergency in ear, nose, and throat practice. Previous studies have demonstrated that intratympanic steroid...
BACKGROUND
Sudden sensorineural hearing loss (SSNHL) is a prevalent emergency in ear, nose, and throat practice. Previous studies have demonstrated that intratympanic steroid therapy (IST) can serve as a salvage treatment for SSNHL after the failure of systemic steroid therapy (SST).
OBJECTIVE
This study aimed to analyze the efficacy of modified IST involving the insertion of a tympanic tube and gelfoam as a salvage treatment for patients with SSNHL, and to explore its associated factors.
METHODS
Totally, 74 patients who were aged 22-81 years with SSNHL were enrolled and allocated to either the control group (n = 25) or the treatment group (n = 49) based on their treatment modalities. All patients received SST lasting for at least 7 days. Subsequently, patients in the treatment group, after SST failure, underwent IST twice a week for 2-6 weeks, while the control group did not. Efficacy was assessed by the improvement in pure tone average at the affected frequency at the beginning and end of IST.
RESULTS
Hearing improvement in all patients after IST in the treatment group was 9.71 ± 14.84 dB, with significant improvement at affected frequencies (250-8000 Hz) compared with the control group (P < 0.05). The findings indicated the duration from the onset of SSNHL to the beginning of IST as an independent factor for pure tone average improvement after treatment (P = 0.002), whereas age, duration of SST, and time of IST were not (P > 0.05).
CONCLUSION
The modified IST was demonstrated to be a safe and effective method as a salvage treatment for SSNHL. This study explored the efficacy of a modified IST approach, incorporating the utilization of tympanic tubes and gelfoam as key components. The findings underscore the advantages of gelfoam as a strategic drug carrier placed in the round window niche. By minimizing drug loss, extending action time, and increasing perilymph concentration, gelfoam enhances the therapeutic impact of IST, contributing to improved hearing outcomes in patients with SSNHL.
PubMed: 38313760
DOI: 10.1016/j.joto.2023.12.001 -
Frontiers in Pharmacology 2024This study evaluated the potential of high-molecular-weight hyaluronic acid (HHA) as an intratympanic (IT) drug delivery vehicle for dexamethasone (D) in treating acute...
This study evaluated the potential of high-molecular-weight hyaluronic acid (HHA) as an intratympanic (IT) drug delivery vehicle for dexamethasone (D) in treating acute hearing loss. We compared the efficacy, safety, and residence time of HHA to the standard-of-care IT drug delivery method. Endoscopic examinations were used to track tympanic membrane (TM) healing post-IT injection. Micro-computed tomography (CT) was used to gauge drug/vehicle persistence in the bulla air space. Histological analyses covered the middle ear, TM, and hair cell counts. Auditory brainstem responses (ABR) were used to measure hearing thresholds, while high-performance liquid chromatography (HPLC) was employed to quantify cochlear perilymph dexamethasone concentrations. The HHA + D group had a notably prolonged drug/vehicle residence time in the bulla (41 ± 27 days) compared to the saline + D group (1.1 ± 0.3 days). Complete TM healing occurred without adverse effects. Histology revealed no significant intergroup differences or adverse outcomes. Hearing recovery trends favored the HHA + D group, with 85.0% of ears showing clinically meaningful improvement. D concentrations in cochlear perilymph were roughly double in the HHA group. HHA is a promising vehicle for IT drug delivery in treating acute hearing loss. It ensures extended residence time, augmented drug concentrations in targeted tissues, and safety. These results highlight the potential for HHA + D to excel beyond existing standard-of-care treatments for acute hearing loss.
PubMed: 38292943
DOI: 10.3389/fphar.2024.1294657 -
Audiology Research Jan 2024Since the discovery of the perilymphatic fistula (PLF), the diagnosis and treatment remain controversial. If successfully recognized, the PLF is surgically repairable...
Since the discovery of the perilymphatic fistula (PLF), the diagnosis and treatment remain controversial. If successfully recognized, the PLF is surgically repairable with an obliteration of the fistula site. Successful treatment has a major impact on patient's quality of life with an improvement in their audiological and vestibular symptoms. To prospectively investigate patients' clinical and audiological evolution with PLF suspicion after middle ear exploration and obliteration of the round and oval window. Prospective comparative study. Tertiary care center. Patients were divided into two groups: Group I consisted of patients where no PLF had been identified intraoperatively at the oval and/or at the round window, and Group II consisted of patients where a fistula had been visualized. Patient assessment was a combination of past medical history, the presence of any risk factors, cochlear and vestibular symptoms, a physical examination, temporal bone imaging, audiograms, and a videonystagmogram (VNG). A total of 98 patients were divided into two groups: 62 in Group I and 36 in Group II. A statistically significant difference regarding gender was observed in Group II (83.3% of males vs. 16.7% of females, = 0.008). A total of 14 cases (4 and 10 in Groups I and II, respectively) were operated for a recurrent PLF. Fat graft material was used in the majority of their previous surgery; however, no difference was found when comparing fat to other materials. In addition, no statistically significant difference was noted between Groups I and II concerning predisposing factors, imaging, VNG, symptom evolution, or a physical exam before the surgery and at 12 months post-operative. However, both groups showed statistically significant hearing and vestibular improvement. On the other hand, the air conduction (AC) and bone conduction (BC) at each frequency were not statistically different between the two groups before surgery but showed statistically significant improvement at 12 months post-operatively, especially for the BC at the frequencies 250 ( = 0.02), 500 ( = 0.0008), and 1000 Hz ( = 0.04). Whenever you suspect a perilymphatic fistula, do not hesitate to explore middle ear and do window obliterations using a tragal perichondrium material. Our data showed that cochlear and vestibular symptoms improved whether a fistula had been identified or not.
PubMed: 38247562
DOI: 10.3390/audiolres14010006