Microanatomy of the human tunnel of Corti structures and cochlear partition-tonotopic variations and transcellular signaling.

Auditory sensitivity and frequency resolution depend on the optimal transfer of sound-induced vibrations from the basilar membrane (BM) to the inner hair cells (IHCs), the principal auditory receptors. There remains a paucity of information on how this is accomplished along the frequency range in the human cochlea. Most of the current knowledge is derived either from animal experiments or human tissue processed after death, offering limited structural preservation and optical resolution. In our study, we analyzed the cytoarchitecture of the human cochlear partition at different frequency locations using high-resolution microscopy of uniquely preserved normal human tissue. The results may have clinical implications and increase our understanding of how frequency-dependent acoustic vibrations are carried to human IHCs. A 1-micron-thick plastic-embedded section (mid-modiolar) from a normal human cochlea uniquely preserved at lateral skull base surgery was analyzed using light and transmission electron microscopy (LM, TEM). Frequency locations were estimated using synchrotron radiation phase-contrast imaging (SR-PCI). Archival human tissue prepared for scanning electron microscopy (SEM) and super-resolution structured illumination microscopy (SR-SIM) were also used and compared in this study. Microscopy demonstrated great variations in the dimension and architecture of the human cochlear partition along the frequency range. Pillar cell geometry was closely regulated and depended on the reticular lamina slope and tympanic lip angle. A type II collagen-expressing lamina extended medially from the tympanic lip under the inner sulcus, here named "accessory basilar membrane." It was linked to the tympanic lip and inner pillar foot, and it may contribute to the overall compliance of the cochlear partition. Based on the findings, we speculate on the remarkable microanatomic inflections and geometric relationships which relay different sound-induced vibrations to the IHCs, including their relevance for the evolution of human speech reception and electric stimulation with auditory implants. The inner pillar transcellular microtubule/actin system's role of directly converting vibration energy to the IHC cuticular plate and ciliary bundle is highlighted.

Synchrotron Phase-Contrast Imaging and Cochlear Otosclerosis: A Case Report.

INTRODUCTION: Otosclerosis is a bone disorder affecting the labyrinthine capsule that leads to conductive and occasionally sensorineural hearing loss. The etiology of otosclerosis remains unknown; factors such as infection, hormones, inflammation, genetics, and autoimmunity have been discussed. Treatment consists primarily of surgical stapes replacement and cochlear implantation. High-resolution computed tomography is routinely used to visualize bone pathology. In the present study, we used synchrotron radiation phase-contrast imaging (SR-PCI) to examine otosclerosis plaques in a temporal bone for the first time. The primary aim was to study their three-dimensional (3D) outline, vascular interrelationships, and connections to the middle ear. METHODS: A donated ear from a patient with otosclerosis who had undergone partial stapedectomy with the insertion of a stapes wire prosthesis was investigated using SR-PCI and compared with a control ear. Otosclerotic lesions were 3D rendered using the composite with shading technique. Scalar opacity and color mapping were adjusted to display volume properties with the removal of bones to enhance surfaces. Vascular bone channels were segmented, and the communications between lesions and the middle ear were established. RESULTS: Fenestral, cochlear, meatal, and vestibular lesions were outlined three-dimensionally. Vascular bone channels were found to be frequently connected to the middle ear mucosa, perilabyrinthine air spaces, and facial nerve vessels. Round window lesions partly embedded the cochlear aqueduct which was pathologically narrowed, while the inferior cochlear vein was significantly dilated in its proximal part. CONCLUSION: Otosclerotic/otospongiotic lesions were imaged for the first time using SR-PCI and 3D rendering. The presence of shunts and abnormal vascular connections to the labyrinth appeared to result in hyper-vascularization, overloading the venous system, and leading to sensorineural hearing loss. We speculate about possible local treatments to alleviate the impact of such critical lesions on the labyrinthine microcirculation.

A combined genome-wide association and molecular study of age-related hearing loss in H. sapiens.

BACKGROUND: Sensorineural hearing loss is one of the most common sensory deficiencies. However, the molecular contribution to age-related hearing loss is not fully elucidated. METHODS: We performed genome-wide association studies (GWAS) for hearing loss-related traits in the UK Biobank (N = 362,396) and selected a high confidence set of ten hearing-associated gene products for staining in human cochlear samples: EYA4, LMX1A, PTK2/FAK, UBE3B, MMP2, SYNJ2, GRM5, TRIOBP, LMO-7, and NOX4. RESULTS: All proteins were found to be expressed in human cochlear structures. Our findings illustrate cochlear structures that mediate mechano-electric transduction of auditory stimuli, neuronal conductance, and neuronal plasticity to be involved in age-related hearing loss. CONCLUSIONS: Our results suggest common genetic variation to influence structural resilience to damage as well as cochlear recovery after trauma, which protect against accumulated damage to cochlear structures and the development of hearing loss over time.

HCN channels in the mammalian cochlea: Expression pattern, subcellular location, and age-dependent changes.

Neuronal diversity in the cochlea is largely determined by ion channels. Among voltage-gated channels, hyperpolarization-activated cyclic nucleotide-gated (HCN) channels open with hyperpolarization and depolarize the cell until the resting membrane potential. The functions for hearing are not well elucidated and knowledge about localization is controversial. We created a detailed map of subcellular location and co-expression of all four HCN subunits across different mammalian species including CBA/J, C57Bl/6N, Ly5.1 mice, guinea pigs, cats, and human subjects. We correlated age-related hearing deterioration in CBA/J and C57Bl/6N with expression levels of HCN1, -2, and -4 in individual auditory neurons from the same cohort. Spatiotemporal expression during murine postnatal development exposed HCN2 and HCN4 involvement in a critical phase of hair cell innervation. The huge diversity of subunit composition, but lack of relevant heteromeric pairing along the perisomatic membrane and axon initial segments, highlighted an active role for auditory neurons. Neuron clusters were found to be the hot spots of HCN1, -2, and -4 immunostaining. HCN channels were also located in afferent and efferent fibers of the sensory epithelium. Age-related changes on HCN subtype expression were not uniform among mice and could not be directly correlated with audiometric data. The oldest mice groups revealed HCN channel up- or downregulation, depending on the mouse strain. The unexpected involvement of HCN channels in outer hair cell function where HCN3 overlaps prestin location emphasized the importance for auditory function. A better understanding may open up new possibilities to tune neuronal responses evoked through electrical stimulation by cochlear implants.

"Reversed polarization" of Na/K-ATPase-a sign of inverted transport in the human endolymphatic sac: a super-resolution structured illumination microscopy (SR-SIM) study.

The human endolymphatic sac (ES) is believed to regulate inner ear fluid homeostasis and to be associated with Meniere's disease (MD). We analyzed the ion transport protein sodium/potassium-ATPase (Na/K-ATPase) and its isoforms in the human ES using super-resolution structured illumination microscopy (SR-SIM). Human vestibular aqueducts were collected during trans-labyrinthine vestibular schwannoma surgery after obtaining ethical permission. Antibodies against various isoforms of Na/K-ATPase and additional solute-transporting proteins, believed to be essential for ion and fluid transport, were used for immunohistochemistry. A population of epithelial cells of the human ES strongly expressed Na/K-ATPase α1, ß1, and ß3 subunit isoforms in either the lateral/basolateral or apical plasma membrane domains. The ß1 isoform was expressed in the lateral/basolateral plasma membranes in mostly large cylindrical cells, while ß3 and α1 both were expressed with "reversed polarity" in the apical cell membrane in lower epithelial cells. The heterogeneous expression of Na/K-ATPase subunits substantiates earlier notions that the ES is a dynamic structure where epithelial cells show inverted epithelial transport. Dual absorption and secretion processes may regulate and maintain inner ear fluid homeostasis. These findings may shed new light on the etiology of endolymphatic hydrops and MD.

Early appearance of key transcription factors influence the spatiotemporal development of the human inner ear.

Expression patterns of transcription factors leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5), transforming growth factor-ß-activated kinase-1 (TAK1), SRY (sex-determining region Y)-box 2 (SOX2), and GATA binding protein 3 (GATA3) in the developing human fetal inner ear were studied between the gestation weeks 9 and 12. Further development of cochlear apex between gestational weeks 11 and 16 (GW11 and GW16) was examined using transmission electron microscopy. LGR5 was evident in the apical poles of the sensory epithelium of the cochlear duct and the vestibular end organs at GW11. Immunostaining was limited to hair cells of the organ of Corti by GW12. TAK1 was immune positive in inner hair cells of the organ of Corti by GW12 and colocalized with p75 neurotrophic receptor expression. Expression for SOX2 was confined primarily to the supporting cells of utricle at the earliest stage examined at GW9. Intense expression for GATA3 was presented in the cochlear sensory epithelium and spiral ganglia at GW9. Expression of GATA3 was present along the midline of both the utricle and saccule in the zone corresponding to the striolar reversal zone where the hair cell phenotype switches from type I to type II. The spatiotemporal gradient of the development of the organ of Corti was also evident with the apex of the cochlea forming by GW16. It seems that highly specific staining patterns of several transcriptions factors are critical in guiding the genesis of the inner ear over development. Our findings suggest that the spatiotemporal gradient in cochlear development extends at least until gestational week 16.

Synchrotron Radiation-Based Reconstruction of the Human Spiral Ganglion: Implications for Cochlear Implantation.

OBJECTIVE: To three-dimensionally reconstruct Rosenthal's canal (RC) housing the human spiral ganglion (SG) using synchrotron radiation phase-contrast imaging (SR-PCI). Straight cochlear implant electrode arrays were inserted to better comprehend the electro-cochlear interface in cochlear implantation (CI). DESIGN: SR-PCI was used to reconstruct the human cochlea with and without cadaveric CI. Twenty-eight cochleae were volume rendered, of which 12 underwent cadaveric CI with a straight electrode via the round window (RW). Data were input into the 3D Slicer software program and anatomical structures were modeled using a threshold paint tool. RESULTS: The human RC and SG were reproduced three-dimensionally with artefact-free imaging of electrode arrays. The anatomy of the SG and its relationship to the sensory organ (Corti) and soft and bony structures were assessed. CONCLUSIONS: SR-PCI and computer-based three-dimensional reconstructions demonstrated the relationships among implanted electrodes, angular insertion depths, and the SG for the first time in intact, unstained, and nondecalcified specimens. This information can be used to assess stimulation strategies and future electrode designs, as well as create place-frequency maps of the SG for optimal stimulation strategies of the human auditory nerve in CI.

Growth and cellular patterning during fetal human inner ear development studied by a correlative imaging approach.

BACKGROUND: Progressive transformation of the otic placode into the functional inner ear during gestational development in humans leads to the acquisition of hearing perception via the cochlea and balance and spatial orientation via the vestibular organ. RESULTS: Using a correlative approach involving micro-computerized tomography (micro-CT), transmission electron microscopy and histological techniques we were able to examine both the morphological and cellular changes associated with human inner ear development. Such an evaluation allowed for the examination of 3D geometry with high spatial and temporal resolution. In concert with gestational progression and growth of the cochlear duct, an increase in the distance between some of the Crista ampullaris is evident in all the specimens examined from GW12 to GW36. A parallel increase in the distances between the macular organs - fetal utricle and saccule - is also evident across the gestational stages examined. The distances between both the utricle and saccule to the three cristae ampullares also increased across the stages examined. A gradient in hair cell differentiation is apparent from apex to base of the fetal cochlea even at GW14. CONCLUSION: We present structural information on human inner ear development across multiple levels of biological organization, including gross-morphology of the inner ear, cellular and subcellular details of hearing and vestibular organs, as well as ultrastructural details in the developing sensory epithelia. This enabled the gathering of detailed information regarding morphometric changes as well in realizing the complex developmental patterns of the human inner ear. We were able to quantify the volumetric and linear aspects of selected gestational inner ear specimens enabling a better understanding of the cellular changes across the fetal gestational timeline. Moreover, these data could serve as a reference for better understanding disorders that arise during inner ear development.

Three-dimensional imaging of the human internal acoustic canal and arachnoid cistern: a synchrotron study with clinical implications.

A thorough knowledge of the gross and micro-anatomy of the human internal acoustic canal (IAC) is essential in vestibular schwannoma removal, cochlear implantation (CI) surgery, vestibular nerve section, and decompression procedures. Here, we analyzed the acoustic-facial cistern of the human IAC, including nerves and anastomoses using synchrotron phase contrast imaging (SR-PCI). A total of 26 fresh human temporal bones underwent SR-PCI. Data were processed using volume-rendering software to create three-dimensional (3D) reconstructions allowing soft tissue analyses, orthogonal sectioning, and cropping. A scalar opacity mapping tool was used to enhance tissue surface borders, and anatomical structures were color-labeled for improved 3D comprehension of the soft tissues. SR-PCI reproduced, for the first time, the variable 3D anatomy of the human IAC, including cranial nerve complexes, anastomoses, and arachnoid membrane invagination (acoustic-facial cistern; an extension of the cerebellopontine cistern) in unprocessed, un-decalcified specimens. An unrecognized system of arachnoid pillars and trabeculae was found to extend between the arachnoid and cranial nerves. We confirmed earlier findings that intra-meatal vestibular schwannoma may grow unseparated from adjacent nerves without duplication of the arachnoid layers. The arachnoid pillars may support and stabilize cranial nerves in the IAC and could also play a role in local fluid hydrodynamics.

Effects of Various Trajectories on Tissue Preservation in Cochlear Implant Surgery: A Micro-Computed Tomography and Synchrotron Radiation Phase-Contrast Imaging Study.

OBJECTIVES: The purpose of this study was to evaluate the three-dimensional (3D) anatomy and potential damage to the hook region of the human cochlea following various trajectories at cochlear implantation (CI). The goal was to determine which of the approaches can avoid lesions to the soft tissues, including the basilar membrane and its suspension to the lateral wall. Currently, there is increased emphasis on conservation of inner ear structures, even in nonhearing preservation CI surgery. DESIGN: Micro-computed tomography and various CI approaches were made in an archival collection of macerated and freshly fixed human temporal bones. Furthermore, synchrotron radiation phase-contrast imaging was used to reproduce the soft tissues. The 3D anatomy was investigated using bony and soft tissue algorithms, and influences on inner ear structures were examined. RESULTS: Micro-computed tomography with 3D rendering demonstrated the topography of the round window (RW) and osseous spiral laminae, while synchrotron imaging allowed reproduction of soft tissues such as the basilar membrane and its suspension around the RW membrane. Anterior cochleostomies and anteroinferior cochleostomies invariably damaged the intracochlear soft tissues while inferior cochleostomies sporadically left inner ear structures unaffected. CONCLUSIONS: Results suggest that cochleostomy approaches often traumatize the soft tissues at the hook region at CI surgery. For optimal structural preservation, the RW approach is, therefore, recommended.

Expression of trans-membrane serine protease 3 (TMPRSS3) in the human organ of Corti.

TMPRSS3 (Trans-membrane Serine Protease 3) is a type II trans-membrane serine protease that has proteolytic activity essential for hearing. Mutations in the gene cause non-syndromic autosomal recessive deafness (DFNB8/10) in humans. Knowledge about its cellular distribution in the human inner ear may increase our understanding of its physiological role and involvement in deafness, ultimately leading to therapeutic interventions. In this study, we used super-resolution structured illumination microscopy for the first time together with transmission electron microscopy to localize the TMPRSS3 protein in the human organ of Corti. Archival human cochleae were dissected out during petroclival meningioma surgery. Microscopy with Zeiss LSM710 microscope achieved a lateral resolution of approximately 80 nm. TMPRSS3 was found to be associated with actin in both inner and outer hair cells. TMPRSS3 was located in cell surface-associated cytoskeletal bodies (surfoskelosomes) in inner and outer pillar cells and Deiters cells and in subcuticular organelles in outer hair cells. Our results suggest that TMPRSS3 proteolysis is linked to hair cell sterociliary mechanics and to the actin/microtubule networks that support cell motility and integrity.

Three-Dimensional Analysis of the Fundus of the Human Internal Acoustic Canal.

OBJECTIVES: Documentation of the nerve components in the internal acoustic canal is essential before cochlea implantation surgery. Interpretations may be challenged by wide anatomical variations of the VIIIth nerve and their ramifications. Malformations may further defy proper nerve identification. DESIGN: Using microcomputed tomography, we analyzed the fundus bone channels in an archival collection of 113 macerated human temporal bones and 325 plastic inner molds. Data were subsequently processed by volume-rendering software using a bony tissue algorithm. Three-dimensional reconstructions were made, and through orthogonal sections, the topographic anatomy was established. RESULTS: The technique provided additional information regarding the anatomy of the nerve foramina/channels of the human fundus region, including variations and destinations. Channel anastomosis were found beyond the level of the fundus. A foramen of the transverse crest was identified. CONCLUSIONS: Three-dimensional reconstructions and cropping outlined the bone canals and demonstrated the highly variable VIIIth nerve anatomy at the fundus of the human inner acoustic canal. Myriad channel interconnections suggested an intricate system of neural interactive pathways in humans. Particularly striking was the variable anatomy of the saccule nerve channels. The results may assist in the preoperative interpretation of the VIIIth nerve anatomy.

Anatomical Characteristics of Facial Nerve and Cochlea Interaction.

OBJECTIVE: The aim was to study the relationship between the labyrinthine portion (LP) of the facial canal and the cochlea in human inner ear molds and temporal bones using micro-CT and 3D rendering. A reduced cochlea-facial distance may spread electric currents from the cochlear implant to the LP and cause facial nerve stimulation. Influencing factors may be the topographic anatomy and otic capsule properties. METHODS: An archival collection of human temporal bones underwent micro-CT and 3D reconstruction. In addition, cochlea-facial distance was assessed in silicone and polyester resin molds, and the association between the LP and upper basal turn of the cochlea was analyzed. RESULTS: Local thinning of the otic capsule and local anatomy may explain the development of cochlea-facial dehiscence, which was found in 1.4%. A reduced cochlea-facial distance was noted in 1 bone with a superior semicircular canal dehiscence but not in bones with superior semicircular canal "blue line." The otic capsule often impinged upon the LP and caused narrowing. CONCLUSION: Micro-CT with 3D rendering offers new possibilities to study the topographic anatomy of the human temporal bone. The varied shape of the cross-section of the LP could often be explained by an "intruding" cochlea.

Super-resolution structured illumination fluorescence microscopy of the lateral wall of the cochlea: the Connexin26/30 proteins are separately expressed in man.

Globally 360 million people have disabling hearing loss and, of these, 32 million are children. Human hearing relies on 15,000 hair cells that transduce mechanical vibrations to electrical signals in the auditory nerve. The process is powered by the endo-cochlear potential, which is produced by a vascularized epithelium that actively transports ions in conjunction with a gap junction (GJ) system. This "battery" is located "off-site" in the lateral wall of the cochlea. The GJ syncytium contains the GJ protein genes beta 2 (GJB2/connexin26 (Cx26)) and 6 (GJB6/connexin30 (Cx30)), which are commonly involved in hereditary deafness. Because the molecular arrangement of these proteins is obscure, we analyze GJ protein expression (Cx26/30) in human cochleae by using super-resolution structured illumination microscopy. At this resolution, the Cx26 and Cx30 proteins were visible as separate plaques, rather than being co-localized in heterotypic channels, as previously suggested. The Cx26 and Cx30 proteins thus seem not to be co-expressed but to form closely associated assemblies of GJ plaques. These results could assist in the development of strategies to treat genetic hearing loss in the future.

The inferior cochlear vein: surgical aspects in cochlear implantation.

The patency of the inferior cochlear vein (ICV) may be challenged in cochlear implantation (CI) due to its location near the round window (RW). This may be essential to consider during selection of different trajectories for electrode insertion aiming at preserving residual hearing. Venous blood from the human cochlea is drained through the ICV. The vein also drains blood from the modiolus containing the spiral ganglion neurons. Surgical interference with this vein could cause neural damage influencing CI outcome. We analyzed the topographical relationship between the RW and ICV bony channel and cochlear aqueduct (CA) from a surgical standpoint. Archival human temporal bones were further microdissected to visualize the CA and its accessory canals (AC1 and AC2). This was combined with examinations of plastic and silicone molds of the human labyrinth. Metric analyses were made using photo stereomicroscopy documenting the proximal portion of the AC1, the internal aperture of the CA and the RW. The mean distance between the AC1 and the anterior rim of the RW was 0.81 mm in bone specimens and 0.67 mm assessed in corrosion casts. The AC1 runs from the floor of the scala tympani through the otic capsule passing parallel to the CA to the posterior cranial fossa. The mean distance between the CA and AC1 canal was 0.31 and 0.25 mm, respectively.

Molecular organization and fine structure of the human tectorial membrane: is it replenished?

Auditory sensitivity and frequency resolution depend on the physical properties of the basilar membrane in combination with outer hair cell-based amplification in the cochlea. The physiological role of the tectorial membrane (TM) in hair cell transduction has been controversial for decades. New insights into the TM structure and function have been gained from studies of targeted gene disruption. Several missense mutations in genes regulating the human TM structure have been described with phenotypic expressions. Here, we portray the remarkable gradient structure and molecular organization of the human TM. Ultrastructural analysis and confocal immunohistochemistry were performed in freshly fixed human cochleae obtained during surgery. Based on these findings and recent literature, we discuss the role of human TMs in hair cell activation. Moreover, the outcome proposes that the α-tectorin-positive amorphous layer of the human TM is replenished and partly undergoes regeneration during life.

Macromolecular organization and fine structure of the human basilar membrane - RELEVANCE for cochlear implantation.

INTRODUCTION: Cochlear micromechanics and frequency tuning depend on the macromolecular organization of the basilar membrane (BM), which is still unclear in man. Novel techniques in cochlear implantation (CI) motivate further analyses of the BM. MATERIALS AND METHODS: Normal cochleae from patients undergoing removal of life-threatening petro-clival meningioma and an autopsy specimen from a normal human were used. Laser-confocal microscopy, high resolution scanning (SEM) and transmission electron microscopy (TEM) were carried out in combination. In addition, one human temporal bone was decellularized and investigated by SEM. RESULTS: The human BM consisted in four separate layers: (1) epithelial basement membrane positive for laminin-ß2 and collagen IV, (2) BM "proper" composed of radial fibers expressing collagen II and XI, (3) layer of collagen IV and (4) tympanic covering layer (TCL) expressing collagen IV, fibronectin and integrin. BM thickness varied both radially and longitudinally (mean 0.55-1.16 µm). BM was thinnest near the OHC region and laterally. CONCLUSIONS: There are several important similarities and differences between the morphology of the BM in humans and animals. Unlike in animals, it does not contain a distinct pars tecta (arcuate) and pectinata. Its width increases and thickness decreases as it travels apically in the cochlea. Findings show that the human BM is thinnest and probably most vibration-sensitive at the outer pillar feet/Deiter cells at the OHCs. The inner pillar and IHCs seem situated on a fairly rigid part of the BM. The gradient design of the BM suggests that its vulnerability increases apical wards when performing hearing preservation CI surgery.

Hearing and Patient Satisfaction Among 19 Patients Who Received Implants Intended for Hybrid Hearing: A Two-Year Follow-Up.

OBJECTIVES: To measure patient satisfaction and correlate to hearing results in partially deaf patients, after hearing preservation cochlear implant surgery with hybrid hearing strategy, and to evaluate the stability of residual low-frequency hearing (LFH) over time. DESIGN: A patient satisfaction survey and a retrospective, 2-year follow-up journal study. Nineteen partially deaf patients intended for hybrid hearing responded to a questionnaire when they had used their cochlear implants for at least a year. The questionnaire consisted of the International Outcome Inventory for Hearing Aids, EuroQol Group visual analogue scale and nine questions about hybrid hearing. Pure-tone audiometry, monosyllables, and hearing in noise test results from the patients' medical records were evaluated and compared with the results from the patient satisfaction survey. RESULTS: All of the patients were satisfied with their CIs. The mean International Outcome Inventory for Hearing Aids score was 29. The CIs provided a major contribution to the speech comprehension of these partially deaf patients. Two years after surgery, the patients' mean binaural score on tests of monosyllables was 58%, and the mean signal to noise ratio was 4.6 dB. We observed ongoing deteriorations in the residual hearing of the operated ears that surpassed the deteriorations observed in the contralateral ears. One month after surgery, the LFH loss (125-500 Hz) was 17 dB, and after 2 years, this loss was 24 dB compared with 5 dB in the nonoperated ear. There were no significant correlations between preserved LFH and patient satisfaction or speech perception results. CONCLUSIONS: Electric stimulation provided a major contribution to speech comprehension of partially deaf patients. The gain reached in speech understanding widely exceeded the downside in losing some residual hearing. All the patients showed a high degree of satisfaction with their CIs regardless of varying hearing preservation.

Possible role of gap junction intercellular channels and connexin 43 in satellite glial cells (SGCs) for preservation of human spiral ganglion neurons : A comparative study with clinical implications.

Human spiral ganglion (SG) neurons show remarkable survival properties and maintain electric excitability for a long time after complete deafness and even separation from the organ of Corti, features essential for cochlear implantation. Here, we analyze and compare the localization and distribution of gap junction (GJ) intercellular channels and connexin 43 (Cx43) in cells surrounding SG cell bodies in man and guinea pig by using transmission electron microscopy and confocal immunohistochemistry. GJs and Cx43 expression has been recognized in satellite glial cells (SGCs) in non-myelinating sensory ganglia including the human SG. In man, SG neurons can survive as mono-polar or "amputated" cells with unbroken central projections following dendrite degeneration and consolidation of the dendrite pole. Cx43-mediated GJ signaling between SGCs is believed to play a key role in this "healing" process and could explain the unique preservation of human SG neurons and the persistence of cochlear implant function.

On the anatomy of the 'hook' region of the human cochlea and how it relates to cochlear implantation.

BACKGROUND: The optimal insertion route for an electrode array in hearing preservation cochlear implantation (CI) surgery is still tentative. Both cochleostomy (CO) and round window (RW) techniques are used today. In the present study we analyzed size variations and topographic anatomy of the 'hook' region of the human cochlea to better comprehend the Testo effects of various electric array insertion modes. MATERIAL AND METHODS: Size variations of the cochlear 'hook' region were assessed in 23 human, microdissected temporal bones by measuring the distances between the oval and round windows, also outlining the spiral ligament/spiral lamina. Influence of size variations on spiral ligament position and fundamentals for different surgical approaches were evaluated in a subset of 'small' and 'large' cochleae performing different types of CO. In addition, the relationship between the microdissected accessory canal housing the inferior cochlear vein and the RW was analyzed. RESULTS: The lateral vestibular wall and the cochlear 'hook' displayed large anatomic variations that greatly influenced the size of the potential surgical area. RESULTS showed that only very inferiorly located CO entered the scala tympani without causing trauma to the spiral ligament and spiral lamina. An inferior approach may challenge the inferior cochlear vein. CONCLUSION: Preoperative assessment of the distance between the round and oval windows may direct the surgeon before CI hearing-preservation surgery. CO techniques, especially in 'small' ears, may lead to frequent damage to the inner ear structures. In those cases with substantial residual hearing, CI surgery may be better performed through a RW approach.