Spiral Ligament Research Articles

Microneedle-Mediated Delivery of siRNA via Liposomal-Based Transfection for Inner Ear Gene Therapy.

Microneedle-mediated intracochlear injection of siRNA-Lipofectamine through the round window membrane (RWM) can be used to transfect cells within the cochlea. Our laboratory has developed 100-μm diameter hollow microneedles for intracochlear injection through the guinea pig RWM. In this study, we test the feasibility of microneedle-mediated injection of siRNA and Lipofectamine, a commonly used reagent with known cellular toxicity, through the RWM for cochlear transfection. Fluorescently labeled scramble siRNA was diluted into Lipofectamine RNAiMax and OptiMEM. One microliter of 5 μM siRNA was injected through the RWM of Hartley guinea pigs at a rate of 1 μl/min (n = 22). In a control group, 1.0 μl of Lipofectamine, with no siRNA, was diluted into OptiMEM and injected in a similar fashion (n = 5). Hearing tests were performed before and either at 24 hours, 48 hours, or 5 days after injection. Afterward, animals were euthanized, and cochleae were harvested for imaging. Control cochleae were processed in parallel to untreated guinea pigs. Fluorescence, indicating successful transfection, was observed within the basal and middle turns of the cochlea with limited distribution in the apex at 24 and 48 hours. Signal was most intense in the organ of Corti, spiral ligament, and spiral ganglion. Little to no fluorescence was observed at 5 days post-injection. No significant changes in auditory brainstem response (ABR) were noted post-perforation at 5 days, suggesting that siRNA-Lipofectamine at low doses does not cause cochlear toxicity. Small volumes of siRNA and Lipofectamine can be effectively delivered to cochlear structures using microneedles, paving the way for atraumatic cochlear gene therapy.

Comparative Histopathologic Analysis of Inner Ear Damage in Meningitis: Otogenic Versus Meningogenic Routes.

To distinguish the patterns of inner ear changes between meningogenic and otogenic routes in meningitis cases. Our hypothesis is that pinpointing distinct patterns linked to each route could aid in the development of diagnostic strategies and targeted therapies. Temporal bones (TBs) from patients with a history of meningitis and histopathological evidence of labyrinthitis were divided into two groups (otogenic and meningogenic). Inner ear histopathological examination was performed to identify qualitative and semi-quantitative changes. This assessment encompassed inflammation patterns, indications of early ossification, hair cell loss, and alterations in the lateral wall, round window membrane, cochlear aqueduct and vestibular aqueduct. Thirty-six TBs were included in the study (otogenic, 21; meningogenic, 15). Generalized labyrinthitis was more common in otogenic cases (100% vs. 53%, p < 0.001). Early signs of cochlear ossification were exclusively observed in otogenic cases (9 TBs). The spiral ligament of otogenic cases has shown a uniform loss of fibrocytes across all cochlear turns, while meningogenic cases showed more severe loss in the apical turn. Otogenic cases exhibited a higher prevalence of severe inflammation of the cochlear aqueduct and endolymphatic sac. Meningogenic cases showed more severe loss of vestibular hair cells in the otolithic organs. Otogenic cases displayed a higher prevalence of changes in the spiral ligament and signs of early ossification, whereas meningogenic cases were associated with a higher degree of vestibular damage. Our findings emphasize the importance of considering the infection route and its implications for timely diagnosis and development of pathology-oriented treatment strategies. NA Laryngoscope, 2024.

Pesticide metabolite 3, 5, 6-trichloro-2-pyridinol causes massive damage to the cochlea resulting in hearing loss in adult mice

Pesticides are a group of extensively used man-made chemicals with high toxicity and strong residues, which are closely related to hearing health. Pesticide metabolite 3, 5, 6-Trichloro-2-pyridinol (TCP) exposure leads to neurotoxicity and auditory cell toxicity. However, whether TCP causes damage to hearing in adult mice is not clear. In this study, adult male C57BL/6 mice continuously exposed to TCP for 21 days showed a dose-dependent elevation of hearing threshold. Outer hair cells and spiral neuron cells were lost in a dose-dependent manner. Type I and V of spiral ligament were severely shrunk and stria vascularis were thinned in mice after 50 and 150 mg/kg TCP exposure. Similarly, ROS levels in the cochlea were significantly increased whereas the activities of anti-oxidation enzymes were decreased after TCP exposure. The expression level of Na+/K+ ATPase was decreased, resulting in cochlear potential disruption. Levels of inflammatory factors (TNF-α and IL-1β), γ-H2AX, and pro-apoptotic-related factors (Bax and cleaved-Caspase 3) were elevated, respectively. These results suggest that TCP can cause oxidative stress, inflammation, and imbalance of cochlear potential in the cochlea, induce cochlear DNA damage and apoptosis, and cause cochlear morphological changes, eventually leading to impaired hearing function.

Cochlear lateral wall changes secondary to hypercholesterolemia and noise exposure in the chinchilla model

Objective: To investigate the effects of hypercholesterolemia on the cochlear lateral wall structures in chinchillas and its impact on the susceptibility of the inner ear structures to noise exposure. Materials and Methods: Fifteen chinchilla temporal bones were selected from the Animal Temporal Bone Collection of the Paparella Otopathology and Pathogenesis Laboratory at the University of Minnesota. The experimental group was subjected to 3-month 1% cholesterol diet, while the control group maintained a standard diet. After 3 months, the experimental group's left ears exposed to noise trauma for 10 minutes while right ears did not. One month later the animals were euthanized, and the temporal bones harvested from the animals underwent histopathological examination with morphometric assessments of stria vascularis (SV) and spiral ligament (SL). Results: Histopathological analysis revealed no significant differences (p &gt; 0.05) in total SL area across cochlear turns between the experimental and control groups. However, distinct variations were observed in SV area within the lower basal (p

Relationship Between Cochlear Lateral Wall Changes and Endolymphatic Hydrops in Otitis Media.

Despite otitis media and various disease processes being associated with endolymphatic hydrops (EH), an exact explanation of the pathophysiology has yet to be reported. This study aimed to investigate the changes in the cochlear lateral wall structures and their potential correlation with the presence and severity of cochlear EH in acute and chronic otitis media cases. The investigations were conducted in both chinchilla animal model and human temporal bone specimens. We studied a total of 15 chinchilla and 25 human temporal bones from our collection, which were categorized into acute otitis media, chronic otitis media (COM), and control groups. Through quantitative analysis, we measured the area of cochlear lateral wall structures and observed the presence and the degree of EH using light microscopy. No significant changes were determined in the area of the spiral ligament (p > 0.05) across the species. However, a significant (p < 0.05) decrease in the mean area of the stria vascularis in the basal turn was identified in COM groups compared to controls of both species. Chinchilla model additionally exhibited pathology extending to the lower mid turn. A negative correlation was found between the mean strial area and the severity of EH in both the animal model and human samples. COM associated with significant changes in the stria vascularis that may lead to significant increase in the degree of EH. The presented animal model exhibited parallel findings with human samples, suggesting its viability as a valuable model for future studies. N/A Laryngoscope, 2024.

Temporal bone marrow of the rat and its connections to the inner ear.

Calvarial bone marrow has been found to be central in the brain immune response, being connected to the dura through channels which allow leukocyte trafficking. Temporal bone marrow is thought to play important roles in relation to the inner ear, but is still largely uncharacterized, given this bone complex anatomy. We characterized the geometry and connectivity of rat temporal bone marrow using lightsheet imaging of cleared samples and microCT. Bone marrow was identified in cleared tissue by cellular content (and in particular by the presence of megakaryocytes); since air-filled cavities are absent in rodents, marrow clusters could be recognized in microCT scans by their geometry. In cleared petrosal bone, autofluorescence allowed delineation of the otic capsule layers. Within the endochondral layer, bone marrow was observed in association to the cochlear base and vestibule, and to the cochlear apex. Cochlear apex endochondral marrow (CAEM) was a separated cluster from the remaining endochondral marrow, which was therefore defined as "vestibular endochondral marrow" (VEM). A much larger marrow island (petrosal non-endochondral marrow, PNEM) extended outside the otic capsule surrounding semicircular canal arms. PNEM was mainly connected to the dura, through bone channels similar to those of calvarial bone, and only a few channels were directed toward the canal periosteum. On the contrary, endochondral bone marrow was well connected to the labyrinth through vascular loops (directed to the spiral ligament for CAEM and to the bony labyrinth periosteum for VEM), and to dural sinuses. In addition, CAEM was also connected to the tensor tympani fossa of the middle ear and VEM to the endolymphatic sac. Endochondral marrow was made up of small lobules connected to each other and to other structures by channels lined by elongated macrophages, whereas PNEM displayed larger lobules connected by channels with a sparse macrophage population. Our data suggest that the rat inner ear is surrounded by bone marrow at the junctions with middle ear and brain, most likely with "customs" role, restricting pathogen spread; a second marrow network with different structural features is found within the endochondral bone layer of the otic capsule and may play different functional roles.

Bioinspired Suspended Sensing Membrane Array with Modulable Wedged-Conductive Channels for Crosstalk-Free and High-Resolution Detection.

High spatial-resolution detection is essential for biomedical applications and human-machine interaction. However, as the sensor array density increases, the miniaturization will lead to interference between adjacent units and deterioration in sensing performance. Here, inspired by the cochlea's sensing structure, a high-density flexible pressure sensor array featuring with suspended sensing membrane with sensitivity-enhanced customized channels is presented for crosstalk-free and high-resolution detection. By imitating the basilar membrane attached to spiral ligaments, a sensing membrane is fixed onto a high-stiffness substrate with cavities, forming a stable braced isolation to provide an excellent crosstalk-free capability (crosstalk coefficient: 47.24dB) with high-density integration (100 units within 1 cm2). Similar to the opening of ion channels in hair cells, the wedge-type expansion of the embedded cracks introduced by stress concentration structures enables a high sensitivity (0.19 kPa-1) and a large measuring range (400kPa). Finally, it demonstrates promising applications in distributed displays and the condition monitoring of medical-surgical intubation.

Hearing loss in type 1 diabetes mellitus: a need to understand precise pathological mechanisms and develop novel therapeutic approaches

This integrative review and perspective article synthesizes current knowledge about the co-morbidity of Type 1 Diabetes (T1D) and sensorineural hearing loss (SNHL), affecting an estimated 9.2 per 1,000 T1D patients annually. Combining data from clinical, preclinical, and mechanistic studies, the article elucidates the complex pathological mechanisms contributing to SNHL in T1D. It is established that T1D accelerates age-related SNHL and brings about detrimental changes in the auditory system, including damage to outer hair cells (OHCs), inner hair cells (IHCs), the stria vascularis (SV), and the spiral ligament (SL). Furthermore, T1D-associated peripheral neuropathy, microvascular damage, and chronic inflammation in the inner ear contribute to auditory deficits. Although some consistency exists between animal models and human conditions, notable discrepancies warrant the refinement of preclinical models to more accurately mirror human clinical scenarios. This perspective article highlights the need for targeted research to bridge existing knowledge gaps and accelerate the development of early-stage interventions for SNHL in T1D patients. Advancements in this field hold the promise of enhancing clinical prognosis and improving the quality of life of individuals having T1D.

Enhanced Cochlear Transduction by AAV9 with High-Concentration Sucrose.

The inner ear is a primary lesion in sensorineural hearing loss and has been a target in gene therapy. The efficacy of gene therapy depends on achieving sufficient levels of transduction at a safe vector dose. Vectors derived from various adeno-associated viruses (AAVs) are predominantly used to deliver therapeutic genes to inner ear cells. AAV9 and its variants vector are attractive candidates for clinical applications since they can cross the mesothelial cell layer and transduce inner hair cells (IHCs), although this requires relatively high doses. In this study, we investigated the effects of sucrose on the transduction of a variant of the AAV9 vector for gene transfer in the inner ear. We found that high concentrations of sucrose increased gene transduction in House Ear Institute-Organ of Corti 1 (HEI-OC1) cells in vitro. In addition, we demonstrated that simultaneous administration of sucrose enhanced the transduction of mouse IHCs and spiral ligament cells using an AAV9 variant vector. The procedure did not increase the thresholds in the auditory brainstem response, suggesting that sucrose had no adverse effect on auditory function. This versatile method may be valuable in the development of novel gene therapies for adult-onset sensorineural hearing loss.

Human Histology after Structure Preservation Cochlear Implantation via Round Window Insertion.

Current surgical techniques aim to preserve intracochlear structures during cochlear implant (CI) insertion to maintain residual cochlear function. The optimal technique to minimize damage, however, is still under debate. The aim of this study is to histologically compare insertional trauma and intracochlear tissue formation in humans with a CI implanted via different insertion techniques. One recent temporal bone from a donor who underwent implantation of a full-length CI (576°) via round window (RW) insertion was compared with nine cases implanted via cochleostomy (CO) or extended round window (ERW) approach. Insertional trauma was assessed on H&E-stained histological sections. 3D reconstructions were generated and virtually re-sectioned to measure intracochlear volumes of fibrosis and neo-ossification. The RW insertion case showed electrode translocation via the spiral ligament. 2/9 CO/ERW cases showed no insertional trauma. The total volume of the cochlea occupied by fibro-osseous tissue was 10.8% in the RW case compared with a mean of 30.6% (range 8.7%-44.8%, N = 9) in the CO/ERW cases. The difference in tissue formation in the basal 5 mm of scala tympani, however, was even more pronounced when the RW case (12.3%) was compared with the cases with a CO/ERW approach (mean of 93.8%, range 81% to 100%, N = 9). Full-length CI insertions via the RW can be minimally traumatic at the cochlear base without inducing extensive fibro-osseous tissue formation locally. The current study further supports the hypothesis that drilling of the cochleostomy with damage to the endosteum incites a local tissue reaction. 4: Case-control study Laryngoscope, 134:945-953, 2024.

Development of cochlear spiral ligament fibrocytes of the common marmoset, a nonhuman model animal

Spiral ligament fibrocytes generate potassium gradients, which hair cells require to convert mechanical sound waves into electrical palsy. Together with the stria vascularis, they regulate endolymph electrolyte homeostasis. Developing spiral ligament fibrocytes and generating endocochlear potential with an appropriate endolymph ion composition are essential for hearing. Understanding spiral ligament fibrocyte development is useful for studying age-related and genetic hearing loss, as well as for regenerative therapy and cochlear immunology. Despite interspecies differences, most studies of cochlear development have been conducted in rodent models due to the difficulty of using human fetal samples. This study investigated the cochlear development of spiral ligament fibrocytes in a small New World monkey species, the common marmoset (Callithrix jacchus). We examined the developmental expression of specific genes in spiral ligament fibrocytes, including those essential for the generation of endolymphatic potential. Our results showed that this animal model of spiral ligament fibrocyte development is similar to that of humans and is a suitable alternative for the analysis of human cochlear development. The time course established in this study will be useful for studying the primate-specific developmental biology of the inner ear, which may lead to novel treatment strategies for human hearing loss.

Influence of CX3CR1 Deletion on Cochlear Hair Cell Survival and Macrophage Expression in Chronic Suppurative Otitis Media.

Our objective was to determine whether the receptor CX3CR1 is necessary for the recruitment of macrophages to the cochlea in chronic suppurative otitis media (CSOM) and if its deletion can prevent hair cell loss in CSOM. CSOM is a neglected disease that afflicts 330 million people worldwide and is the most common cause of permanent hearing loss among children in the developing world. It is characterized by a chronically discharging infected middle ear. We have previously demonstrated that CSOM causes macrophage associated sensory hearing loss. The receptor CX3CR1 is expressed on macrophages, which have been shown to be increased at the time point of outer hair cell (OHC) loss in CSOM. In this report, we examine the influence of CX3CR1 deletion (CX3CR1-/-) in a validated model of Pseudomonas aeruginosa (PA) CSOM. The data show no difference in OHC loss between the CX3CR1-/- CSOM group and CX3CR1+/+ CSOM group (p = 0.28). We observed partial OHC loss in the cochlear basal turn, no OHC loss in the middle and apical turns in both CX3CR1-/- and CX3CR1+/+ CSOM mice at 14 days after bacterial inoculation. No inner hair cell (IHC) loss was found in all cochlear turns in all groups. We also counted F4/80 labeled macrophages in the spiral ganglion, spiral ligament, stria vascularis and spiral limbus of the basal, middle, and apical turn in cryosections. We did not find a significant difference in the total number of cochlear macrophages between CX3CR1-/- mice and CX3CR1+/+ mice (p = 0.97). The data did not support a role for CX3CR1 macrophage associated HC loss in CSOM.

Mitochondrial alterations in the cochlea of Cdk5rap1-knockout mice with age-related hearing loss.

Previous studies have revealed that age-related hearing loss (AHL) in Cdk5 regulatory subunit-associated protein 1 (Cdk5rap1)-knockout mice is associated with pathology in the cochlea. Here, we aimed to identify mitochondrial alterations in the cochlea of Cdk5rap1-knockout mice with AHL. Mitochondria in the spiral ganglion neurons (SGNs) and hair cells (HCs) were normal despite senescence; however, the mitochondria of types I, II, and IV spiral ligament fibrocytes were ballooned, damaged, and ballooned, respectively, in the stria vascularis. Our results suggest that the accumulation of dysfunctional mitochondria in the lateral wall, rather than the loss of HCs and SGNs, leads to the onset of AHL. Our results provide valuable information regarding the underlying mechanisms of AHL and the relationship between aberrant tRNA modification-induced hearing loss and mitochondrial dysfunction.

Dysregulation of fetal-derived cochlear resident tissue macrophages mediates CMV-associated sensorineural hearing loss

Abstract Cytomegalovirus (CMV) is the most common congenital viral infection in the developed world and the leading cause of non-genetic sensorineural hearing loss (SNHL) in children. Congenital CMV causes progressive SNHL long after acute infection has resolved, suggesting a lasting effect on the developing host immune response in the cochlea. Using fate-mapping models, we investigated the contribution of fetal-derived resident tissue macrophages (RTMs) to normal cochlear development and function, and their role in mediating CMV-associated SNHL. We uncovered dual contribution of fetal-derived cochlear RTMs (F4/80 hiCD11b lo) from yolk sac (YS) and fetal liver (FL) hematopoiesis at birth. YS-derived RTMs naturally recede postnatally after cochlea development, but remain in key tissues, such as the spiral ligament and stria vascularis, through adulthood. Depletion of fetal-derived RTMs by anti-CSF1R blocking Ab led to SNHL and impairments to cochlear architecture. Similarly, embryonic deletion of YS-derived RTMs by induced deletion of CSF1R leads to SNHL at high frequencies. During acute CMV infection, RTMs expand and become transcriptionally dysregulated in developmental programs, including tissue remodeling, chemorepulsion, otic vesicle morphogenesis, and FGF signaling. Importantly, analysis of CSF1R-Cre labeling suggests YS-derived RTMs retract in response to CMV infection, suggesting RTM expansion is caused by infiltration of BM-derived macrophages. Ongoing work examines spatial distribution of fetal-derived cochlear RTMs, transcriptional differences between YS, FL, and BM-derived RTMs in response to CMV, and how replacement of fetal-derived RTMs with BM-derived RTMs affects tissue function and response to CMV. Supported by grants from NIAID (T32 5T32AI138945) and University of Utah molecular medicine and immunology, inflammation and infectious disease (3i) initiative

Whole-exome sequencing for screening noise-induced hearing loss susceptibility genes

Background High-throughput sequencing of genes indicating susceptibility to noise-induced hearing loss has not previously been reported. Aims/Objectives To identify and analyze genes associated with susceptibility to noise-induced hearing loss (NIHL) and characterize differences in susceptibility to hearing loss by genotype. Material and methods Pure tone audiometry tests were performed on 113 workers exposed to high-intensity noise. Whole-exome sequencing (WES) was conducted and NIHL susceptibility genes screened for training unsupervised and supervised machine learning models. Immunofluorescence staining of mouse cochlea was used to observe patterns of NIHL susceptibility gene expression. Results Participants were divided into a NIHL and a control group, according to the results of audiometry tests. Seventy-three possible NIHL susceptibility genes were input into the machine learning model. Two subgroups of NIHL could be distinguished by unsupervised machine learning and the classification was evaluated by the supervised machine learning algorithm. The VWF gene had the highest mutation frequency in the NIHL group and was expressed mainly in the spiral ligament. Conclusions and significance NIHL susceptibility genes were screened and NIHL subgroups could be distinguished. VWF may be a novel NIHL susceptibility gene.

Immunohistochemical localization of glucocorticoid receptors in the human cochlea

In the present study we investigated the localization of glucocorticoid receptors (GCR) in the human inner ear using immunohistochemistry. Celloidin-embedded cochlear sections of patients with normal hearing (n = 5), patients diagnosed with MD (n = 5), and noise induced hearing loss (n = 5) were immunostained using GCR rabbit affinity-purified polyclonal antibodies and secondary fluorescent or HRP labeled antibodies. Digital fluorescent images were acquired using a light sheet laser confocal microscope. In celloidin-embedded sections GCR-IF was present in the cell nuclei of hair cells and supporting cells of the organ of Corti. GCR-IF was detected in cell nuclei of the Reisner’s membrane. GCR-IF was seen in cell nuclei of the stria vascularis and the spiral ligament. GCR-IF was found in the spiral ganglia cell nuclei, however, spiral ganglia neurons showed no GCR-IF. Although GCRs were found in most cell nuclei of the cochlea, the intensity of IF was differential among the different cell types being more intense in supporting cells than in sensory hair cells. The differential expression of GCR receptors found in the human cochlea may help to understand the site of action of glucocorticoids in different ear diseases.

Treatment of chronic mallet finger with swan neck deformity using a modified Spiral Oblique Retinacular Ligament (SORL) reconstruction procedure: A case series and technical note.

Chronic terminal extensor tendon injury produces mallet deformity and secondary swan neck deformity. It can be found in neglect cases and in a failed cases after conservative treatment or primary surgical repair. Surgery is considered in cases with extensor lag of more than 30° and functional deficit. Reconstruction of the spiral oblique retinacular ligament (SORL) has been reported in literatures to correct swan neck deformity by a dynamic mechanical basis. Three cases of chronic mallet finger associated with swan neck deformity were treated by the modified technique of SORL reconstruction. Range of motion (ROM) of distal interphalangeal (DIP) joints and proximal interphalangeal (PIP) joints were measured along with the complications. The clinical outcome was reported using the Crawford's criteria. All patients had an average age of 34years (20-54). Average time to surgery was 16.67months (2-24) and average of DIP extension lag was 66.67°. All patient gave excellent Crawford criteria at the latest follow up (average 15.3months). The average PIP joint ROM were -1.60 (00 to -50) of extension and 1100 (1000-1200) of flexion for the PIP joint and -1.60 (00 to -50) of extension and 83.330 (800-850) of flexion for the DIP joint. We present our technique to manage chronic mallet injury which only utilized two skin incisions and one button at the distal phalanx to minimize risk of skin necrosis and patient discomfort. This procedure can be considered as one of the options for the treatment of chronic mallet finger deformity associated with swan neck deformity.

Visualizing Collagen Fibrils in the Cochlea's Tectorial and Basilar Membranes Using a Fluorescently Labeled Collagen-Binding Protein Fragment.

A probe that binds to unfixed collagen fibrils was used to image the shapes and fibrous properties of the TM and BM. The probe (CNA35) is derived from the bacterial adhesion protein CNA. We present confocal images of hydrated gerbil TM, BM, and other cochlear structures stained with fluorescently labeled CNA35. A primary purpose of this article is to describe the use of the CNA35 collagen probe in the cochlea. Recombinant poly-histidine-tagged CNA35 was expressed in Escherichia coli, purified by cobalt-affinity chromatography, fluorescence labeled, and further purified by gel filtration chromatography. Cochleae from freshly harvested gerbil bullae were irrigated with and then incubated in CNA35 for periods ranging from 2h - overnight. The cochleae were fixed, decalcified, and dissected. Isolated cochlear turns were imaged by confocal microscopy. The CNA35 probe stained the BM and TM, and volumetric imaging revealed the shape of these structures and the collagen fibrils within them. The limbal zone of the TM stained intensely. In samples from the cochlear base, intense staining was detected on the side of the TM that faces hair cells. In the BM pectinate zone, staining was intense at the upper and lower boundaries. The BM arcuate zone was characterized by a prominent longitudinal collagenous structure. The spiral ligament, limbus and lamina stained for collagen, and within the spiral limbus the habenula perforata were outlined with intense staining. The CNA35 probe provides a unique and useful view of collagenous structures in the cochlea.

Aldosterone inhibits Dot1l expression in guinea pig cochlea

BackgroundAldosterone relieves transcriptional repression of epithelial sodium channel (ENaC) by inhibiting Dot1a and Af9 expression and their interaction with ENaC promoter in various tissues. Expressions of ENaC and Af9 in inner ear have been identified. However, it is not known how Dot1l is regulated by aldosterone in inner ear.MethodsTwenty-eight adult guinea pigs were randomly divided into the control group and treatment group. Aldosterone 1 mg/kg/d was injected intraperitoneally in the treatment group and saline in the control group for 7 days. Animals were killed 1 month later following auditory brainstem response examination. Histomorphology of cochlea was detected with hematoxylin–eosin staining, and Dot1l expression was examined with immunohistochemistry and Western blot.ResultsThere was no significant difference in ABR thresholds before and after injection of aldosterone or saline in either group. Endolymphatic hydrops was found in 75% of animals in the treatment group. Dot1l was found in both groups in the stria vascularis, Reissner’s membrane, spiral limbus, organ of Corti and spiral ligament. Dot1l expression in the treatment group was decreased by aldosterone.ConclusionsDot1l in guinea pig cochlea is inhibited by aldosterone with induction of endolymphatic hydrops. Dot1l may be closely related to endolymph regulation by aldosterone and to pathogenesis of Meniere’s disease.

Imaging of the human cochlea using micro-computed tomography before and after cochlear implantation: comparison with cone-beam computed tomography.

Analysis of cochlear structures and postoperative temporal bone (TB) imaging are gaining importance in the evaluation of cochlear implantation (CI°). Our aims were to explore the microarchitecture of human cochlea using micro-computed tomography (μCT), analyze electrode's placement inside cochlea after CI°, and compare pre-/post-implantation μCT scans with cone-beam CT (CBCT) scans of same TBs. Cadaveric TBs were scanned using μCT and CBCT then underwent CI° using straight electrodes. Thereafter, they underwent again μCT and CBCT-imaging. Ten TBs were studied. μCT allowed visualization of scala tympani, scala vestibuli, basilar membrane, osseous spiral lamina, crista fenestrae, and spiral ligament. CBCT showed same structures except spiral ligament and crista fenestrae. After CI°, μCT and CBCT displayed the scalar location and course of electrode array within the cochlea. There were 7 cases of atraumatic electrode insertion and 3 cases of insertion trauma: basilar membrane elevation, electrode foldover with limited migration into scala vestibuli, and electrode kinking with limited migration into scala vestibuli. Insertion trauma was not correlated with cochlea's size or crista's maximal height but with round window membrane diameter. Resolution of μCT was higher than CBCT but electrode artifacts were similar. μCT was accurate in visualizing cochlear structures, and course and scalar position of electrode array inside cochlea with any possible trauma to cochlea or array. CBCT offers a good alternative to μCT in clinical practice for cochlear imaging and evaluation of CI°, with lower radiation and higher resolution than multi-slice CT. Difficulties related to non-traumatic CI° are multifactorial.