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1.
J Assoc Res Otolaryngol ; 24(4): 441-452, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37407801

RESUMO

PURPOSE: The osseous spiral lamina (OSL) is an inner cochlear bony structure that projects from the modiolus from base to apex, separating the cochlear canal into the scala vestibuli and scala tympani. The porosity of the OSL has recently attracted the attention of scientists due to its potential impact on the overall sound transduction. The bony pillars between the vestibular and tympanic plates of the OSL are not always visible in conventional histopathological studies, so imaging of such structures is usually lacking or incomplete. With this pilot study, we aimed, for the first time, to anatomically demonstrate the OSL in great detail and in 3D. METHODS: We measured width, thickness, and porosity of the human OSL by microCT using increasing nominal resolutions up to 2.5-µm voxel size. Additionally, 3D models of the individual plates at the basal and middle turns and the apex were created from the CT datasets. RESULTS: We found a constant presence of porosity in both tympanic plate and vestibular plate from basal turn to the apex. The tympanic plate appears to be more porous than vestibular plate in the basal and middle turns, while it is less porous in the apex. Furthermore, the 3D reconstruction allowed the bony pillars that lie between the OSL plates to be observed in great detail. CONCLUSION: By enhancing our comprehension of the OSL, we can advance our comprehension of hearing mechanisms and enhance the accuracy and effectiveness of cochlear models.


Assuntos
Cóclea , Audição , Humanos , Lâmina Espiral , Microtomografia por Raio-X , Projetos Piloto , Cóclea/patologia , Audição/fisiologia
2.
Hear Res ; 418: 108458, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35334332

RESUMO

Hearing loss in patients with vestibular schwannoma (VS) is commonly attributed to mechanical compression of the auditory nerve, though recent studies suggest that this retrocochlear pathology may be augmented by cochlear damage. Although VS-associated loss of inner hair cells, outer hair cells, and spiral ganglion cells has been reported, it is unclear to what extent auditory-nerve peripheral axons are damaged in VS patients. Understanding the degree of damage VSs cause to auditory nerve fibers (ANFs) is important for accurately modeling clinical outcomes of cochlear implantation, which is a therapeutic option to rehabilitate hearing in VS-affected ears. A retrospective analysis of human temporal-bone histopathology was performed on archival specimens from the Massachusetts Eye and Ear collection. Seven patients met our inclusion criteria based on the presence of sporadic, unilateral, untreated VS. Tangential sections of five cochlear regions were stained with hematoxylin and eosin, and adjacent sections were stained to visualize myelinated ANFs and efferent fibers. Following confocal microscopy, peripheral axons of ANFs within the osseous spiral lamina were quantified manually, where feasible, and with a "pixel counting" method, applicable to all sections. ANF density was substantially reduced on the VS side compared to the unaffected contralateral side. In the upper basal turn, a significant difference between the VS side and unaffected contralateral side was found using both counting methods, corresponding to the region tuned to 2000 Hz. Even spiral ganglion cells (SGCs) contralateral to VS were affected by the tumor as the majority of contralateral SGC counts were below average for age. This observation provides histological insight into the clinical observation that unilateral vestibular schwannomas pose a long-term risk of progression of hearing loss in the contralateral ear as well. Our pixel counting method for ANF quantification in the osseous spiral lamina is applicable to other pathologies involving sensorineural hearing loss. Future research is needed to classify ANFs into morphological categories, accurately predict their electrical properties, and use this knowledge to inform optimal cochlear implant programming strategies.


Assuntos
Surdez , Perda Auditiva , Neuroma Acústico , Humanos , Nervo Coclear/patologia , Surdez/patologia , Perda Auditiva/patologia , Neuroma Acústico/patologia , Estudos Retrospectivos , Gânglio Espiral da Cóclea/patologia , Lâmina Espiral
3.
J Histochem Cytochem ; 69(11): 731-739, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34666550

RESUMO

In the vertebrate cochlea, the reticular lamina seals the organ of Corti against the endolymph filled scala media. After noise exposure, fast alterations in the endothelial nitric oxide synthase (eNOS) expression level were identified in this cochlear structure. Minor amounts of nitric oxide (NO) produced by eNOS or applied by NO donors such as S-nitroso-N-acetyl-penicillamine (SNAP) might protect this vulnerable part of the organ of Corti, on the line of gap junctions of supporting cells and cochlear microcirculation. In n=5 anesthetized guinea pigs, SNAP was intravenously applied in two concentrations. Six untreated animals served as controls. The cochleae were removed and prepared for immunoelectron microscopy using specific gold-labeled anti-eNOS antibodies. The density of the gold particles was quantified for seven cellular regions in the reticular lamina at the ultrastructural level. Following SNAP application, a significant increase in eNOS expression (+176%) was detected compared with controls (p=0.012). The increase occurred mainly in actin-rich cuticular structures and the prominent microtubules bundles. Correlation analysis revealed three clear and five moderate cellular associations for controls, whereas only one clear and one moderate after SNAP application. Thus, application of the NO donor SNAP resulted in an increase in eNOS expression in distinct regions of the reticular lamina.


Assuntos
Doadores de Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Órgão Espiral/metabolismo , Lâmina Espiral/metabolismo , Animais , Cobaias , Masculino
4.
J Assoc Res Otolaryngol ; 21(2): 171-182, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32166603

RESUMO

The classic view of cochlear partition (CP) motion, generalized to be for all mammals, was derived from basal-turn measurements in laboratory animals. Recently, we reported motion of the human CP in the cochlear base that differs substantially from the classic view. We described a human soft tissue "bridge" (non-existent in the classic view) between the osseous spiral lamina (OSL) and basilar membrane (BM), and showed how OSL and bridge move in response to sound. Here, we detail relevant human anatomy to better understand the relationship between form and function. The bridge and BM have similar widths that increase linearly from base to apex, whereas the OSL width decreases from base to apex, leading to an approximately constant total CP width throughout the cochlea. The bony three-dimensional OSL microstructure, reconstructed from unconventionally thin, 2-µm histological sections, revealed thin, radially wide OSL plates with pores that vary in size, extent, and distribution with cochlear location. Polarized light microscopy revealed collagen fibers in the BM that spread out medially through the bridge to connect to the OSL. The long width and porosity of the OSL may explain its considerable bending flexibility. The similarity of BM and bridge widths along the cochlea, both containing continuous collagen fibers, may make them a functional unit and allow maximum CP motion near the bridge-BM boundary, as recently described. These anatomical findings may help us better understand the motion of the structures surrounding the organ of Corti and how they shape the input to the cochlear sensory mechanism.


Assuntos
Lâmina Espiral/anatomia & histologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Membrana Basilar/anatomia & histologia , Criança , Cóclea/fisiologia , Feminino , Colágenos Fibrilares , Humanos , Imageamento Tridimensional , Masculino , Microscopia , Pessoa de Meia-Idade , Lâmina Espiral/diagnóstico por imagem , Adulto Jovem
5.
J Assoc Res Otolaryngol ; 20(5): 461-474, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31407107

RESUMO

Although anatomical development of the cochlear duct is thought to be complete by term birth, human newborns continue to show postnatal immaturities in functional measures such as otoacoustic emissions (OAEs). Some of these OAE immaturities are no doubt influenced by incomplete maturation of the external and middle ears in infants; however, the observed prolongation of distortion-product OAE phase-gradient delays in newborns cannot readily be explained by conductive factors. This functional immaturity suggests that the human cochlea at birth may lack fully adult-like traveling-wave motion. In this study, we analyzed temporal-bone sections at the light microscopic level in newborns and adults to quantify dimensions and geometry of cochlear structures thought to influence the mechanical response of the cochlea. Contrary to common belief, results show multiple morphological immaturities along the length of the newborn spiral, suggesting that important refinements in the size and shape of the sensory epithelium and associated structures continue after birth. Specifically, immaturities of the newborn basilar membrane and organ of Corti are consistent with a more compliant and less massive cochlear partition, which could produce longer DPOAE delays and a shifted frequency-place map in the neonatal ear.


Assuntos
Órgão Espiral/anatomia & histologia , Adulto , Fatores Etários , Membrana Basilar/anatomia & histologia , Cóclea/anatomia & histologia , Ducto Coclear/anatomia & histologia , Humanos , Recém-Nascido , Órgão Espiral/crescimento & desenvolvimento , Lâmina Espiral/anatomia & histologia
6.
Medicine (Baltimore) ; 98(24): e15991, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31192940

RESUMO

Little is known regarding differences between model-based iterative reconstruction (MBIR) and hybrid iterative reconstruction (HIR) in temporal bone computed tomography (CT). This study compared the ability to depict microstructures in temporal bone in quarter-detector CT (QDCT) between MBIR and HIR.Sixty-two temporal bones in 31 consecutive adult patients who underwent QDCT were included. Reconstruction was performed with Forward projected model-based Iterative Reconstruction SoluTion (FIRST) BONE mild mode and Adaptive Iterative Dose Reduction 3D (AIDR3D) enhanced mild mode. Imaging quality was graded for 3 microstructures (spiral osseous lamina, tympanic membrane, and singular canal).Spiral osseous lamina was significantly well-delineated in the AIDR3D enhanced group, compared with the FIRST group. In nearly all cases with FIRST, spiral osseous lamina was poorly defined. Although there was no significant difference, depiction of the tympanic membrane and singular canal tended to be better with AIDR3D enhanced mode.Routine reconstruction for preoperative temporal bone CT should be performed with HIR, rather than MBIR.


Assuntos
Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Lâmina Espiral/anatomia & histologia , Osso Temporal/anatomia & histologia , Tomografia Computadorizada por Raios X/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Lâmina Espiral/diagnóstico por imagem , Osso Temporal/diagnóstico por imagem
7.
Hear Res ; 371: 105-116, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30530270

RESUMO

Using transgenic fluorescent reporter mice in combination with an established tissue clearing method, we detail heretofore optically opaque regions of the spiral lamina and spiral limbus where the auditory peripheral nervous system is located and provide insight into changes in cochlear vascular density with ageing. We found a relatively dense and branched vascular network in young adults, but a less dense and thinned network in aged adults. Significant reduction in vascular density starts early at the age of 180 days in the region of the spiral limbus (SL) and continues into old age at 540 days. Loss of vascular volume in the region of spiral ganglion neurons (SGN) is delayed until the age of 540 days. In addition, we observed that two vascular accessory cells are closely associated with the microvascular system: perivascular resident macrophages and pericytes. Morphologically, perivascular resident macrophages undergo drastic changes from postnatal P7 to young adult (P30). In postnatal animals, most perivascular resident macrophages exhibit a spherical or nodular shape. In young adult mice, the majority of perivascular resident macrophages are elongated and display an orientation parallel to the vessels. In our imaging, some of the perivascular resident macrophages are caught in the act of transmigrating from the blood circulation. Pericytes also display morphological heterogeneity. In the P7 mice, pericytes are prominent on the capillary walls, relatively large and punctate, and less uniform. In contrast, pericytes in the P30 mice are relatively flat and uniform, and less densely distributed on the vascular network. With triple fluorescence labeling, we did not find obvious physical connection between the two systems, unlike neuronal-vascular coupling found in brain. However, using a fluorescent (FITC-conjugated dextran) tracer and the enzymatic tracer horseradish peroxidase (HRP), we observed robust neurovascular exchange, likely through transcytotic transport, evidenced by multiple vesicles present in the endothelial cells. Taken together, our data demonstrate the effectiveness of tissue-clearing methods as an aid in imaging the vascular architecture of the SL and SGNs in whole mounted mouse cochlear preparations. Structure is indicative of function. The finding of differences in vascular structure in postnatal and young adult mice may correspond with variation in hearing refinement after birth and indicate the status of functional activity. The decrease in capillary network density in the older animals may reflect the decreased energy demand from peripheral neural activity. The finding of active transcytotic transport from blood to neurons opens a potential therapeutic avenue for delivery of various growth factors and gene vectors into the inner ear to target SGNs.


Assuntos
Microvasos/anatomia & histologia , Gânglio Espiral da Cóclea/irrigação sanguínea , Envelhecimento/patologia , Animais , Macrófagos/citologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Microscopia Confocal , Microscopia Eletrônica de Transmissão , Microvasos/citologia , Pericitos/citologia , Sistema Nervoso Periférico/irrigação sanguínea , Lâmina Espiral/irrigação sanguínea
8.
Elife ; 72018 10 22.
Artigo em Inglês | MEDLINE | ID: mdl-30346274

RESUMO

Distinct anatomical and spectral channels are thought to play specialized roles in the communication within cortical networks. While activity in the alpha and beta frequency range (7 - 40 Hz) is thought to predominantly originate from infragranular cortical layers conveying feedback-related information, activity in the gamma range (>40 Hz) dominates in supragranular layers communicating feedforward signals. We leveraged high precision MEG to test this proposal, directly and non-invasively, in human participants performing visually cued actions. We found that visual alpha mapped onto deep cortical laminae, whereas visual gamma predominantly occurred more superficially. This lamina-specificity was echoed in movement-related sensorimotor beta and gamma activity. These lamina-specific pre- and post- movement changes in sensorimotor beta and gamma activity suggest a more complex functional role than the proposed feedback and feedforward communication in sensory cortex. Distinct frequency channels thus operate in a lamina-specific manner across cortex, but may fulfill distinct functional roles in sensory and motor processes.


Assuntos
Retroalimentação Sensorial , Desempenho Psicomotor/fisiologia , Córtex Sensório-Motor/fisiologia , Córtex Visual/fisiologia , Adulto , Ritmo alfa , Ritmo beta , Mapeamento Encefálico , Feminino , Ritmo Gama , Humanos , Masculino , Movimento/fisiologia , Lobo Parietal/fisiologia , Lâmina Espiral/fisiologia
9.
Ups J Med Sci ; 123(1): 9-18, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29537931

RESUMO

OBJECTIVE: We used synchrotron radiation phase contrast imaging (SR-PCI) to study the 3D microanatomy of the basilar membrane (BM) and its attachment to the spiral ligament (SL) (with a conceivable secondary spiral lamina [SSL] or secondary spiral plate) at the round window membrane (RWM) in the human cochlea. The conception of this complex anatomy may be essential for accomplishing structural preservation at cochlear implant surgery. MATERIAL AND METHODS: Sixteen freshly fixed human temporal bones were used to reproduce the BM, SL, primary and secondary osseous spiral laminae (OSL), and RWM using volume-rendering software. Confocal microscopy immunohistochemistry (IHC) was performed to analyze the molecular constituents. RESULTS: SR-PCI reproduced the soft tissues including the RWM, Reissner's membrane (RM), and the BM attachment to the lateral wall (LW) in three dimensions. A variable SR-PCI contrast enhancement was recognized in the caudal part of the SL facing the scala tympani (ST). It seemed to represent a SSL allied to the basilar crest (BC). The SSL extended along the postero-superior margin of the round window (RW) and immunohistochemically expressed type II collagen. CONCLUSIONS: Unlike in several mammalian species, the human SSL is restricted to the most basal portion of the cochlea around the RW. It anchors the BM and may influence its hydro-mechanical properties. It could also help to shield the BM from the RW. The microanatomy should be considered at cochlear implant surgery.


Assuntos
Implante Coclear/métodos , Lâmina Espiral/diagnóstico por imagem , Membrana Basilar/anatomia & histologia , Membrana Basilar/diagnóstico por imagem , Humanos , Imuno-Histoquímica , Janela da Cóclea/anatomia & histologia , Janela da Cóclea/diagnóstico por imagem , Lâmina Espiral/anatomia & histologia
10.
Hear Res ; 361: 138-151, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29426600

RESUMO

The endocochlear potential (EP) provides part of the electrochemical drive for sound-driven currents through cochlear hair cells. Intense noise exposure (110 dB SPL, 2 h) differentially affects the EP in three inbred mouse strains (C57BL/6 [B6], CBA/J [CBA], BALB/cJ [BALB]) (Ohlemiller and Gagnon, 2007, Hearing Research 224:34-50; Ohlemiller et al., 2011, JARO 12:45-58). At least for mice older than 3 mos, B6 mice are unaffected, CBA mice show temporary EP reduction, and BALB mice may show temporary or permanent EP reduction. EP reduction was well correlated with histological metrics for injury to stria vascularis and spiral ligament, and little evidence was found for holes or tears in the reticular lamina that might 'short out' the EP. Thus we suggested that the genes and processes that underlie the strain EP differences primarily impact cochlear lateral wall, not the organ of Corti. Our previous work did not test the range of noise exposure conditions over which strain differences apply. It therefore remained possible that the relation between exposure severity and acute EP reduction simply has a higher exposure threshold in B6 mice compared to CBA and BALB. We also did not test for age dependence. It is well established that young adult animals are especially vulnerable to noise-induced permanent threshold shifts (NIPTS). It is unknown, however, whether heightened vulnerability of the lateral wall contributes to this condition. The present study extends our previous work to multiple noise exposure levels and durations, and explicitly compares young adult (6-7 wks) and older mice (>4 mos). We find that the exposure level-versus-acute EP relation is dramatically strain-dependent, such that B6 mice widely diverge from both CBA and BALB. For all three strains, however, acute EP reduction is greater in young mice. Above 110 dB SPL, all mice exhibited rapid and severe EP reduction that is likely related to tearing of the reticular lamina. By contrast, EP-versus-noise duration examined at 104 dB suggested that different processes contribute to EP reduction in young and older mice. The average EP falls to a constant level after ∼7.5 min in older mice, but progressively decreases with further exposure in young mice. Confocal microscopy of organ of Corti surface preparations stained for phalloidin and zonula occludens-1 (ZO-1) indicated this corresponds to rapid loss of outer hair cells (OHCs) and formation of both holes and tears in the reticular lamina of young mice. In addition, when animals exposed at 119 dB were allowed to recover for 1 mo, only young B6 mice showed collapse of the EP to ≤5 mV. Confocal analysis suggested novel persistent loss of tight junctions in the lateral organ of Corti. This may allow paracellular leakage that permanently reduces the EP. From our other findings, we propose that noise-related lateral wall pathology in young CBA and BALB mice promotes hair cell loss and opening of the reticular lamina. The heightened vulnerability of young adult animals to noise exposure may in part reflect special sensitivity of the organ of Corti to acute lateral wall dysfunction at younger ages. This feature appears genetically modifiable.


Assuntos
Potenciais Evocados Auditivos , Células Ciliadas Auditivas/patologia , Perda Auditiva Provocada por Ruído/patologia , Ruído , Lâmina Espiral/patologia , Fatores Etários , Animais , Limiar Auditivo , Simulação por Computador , Modelos Animais de Doenças , Células Ciliadas Auditivas/metabolismo , Perda Auditiva Provocada por Ruído/metabolismo , Perda Auditiva Provocada por Ruído/fisiopatologia , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos CBA , Modelos Biológicos , Especificidade da Espécie , Lâmina Espiral/metabolismo , Lâmina Espiral/fisiopatologia , Junções Íntimas/metabolismo , Junções Íntimas/patologia , Fatores de Tempo , Proteína da Zônula de Oclusão-1/metabolismo
11.
Sci Rep ; 7(1): 7500, 2017 08 08.
Artigo em Inglês | MEDLINE | ID: mdl-28790422

RESUMO

The human inner ear has an intricate spiral shape often compared to shells of mollusks, particularly to the nautilus shell. It has inspired many functional hearing theories. The reasons for this complex geometry remain unresolved. We digitized 138 human cochleae at microscopic resolution and observed an astonishing interindividual variability in the shape. A 3D analytical cochlear model was developed that fits the analyzed data with high precision. The cochlear geometry neither matched a proposed function, namely sound focusing similar to a whispering gallery, nor did it have the form of a nautilus. Instead, the innate cochlear blueprint and its actual ontogenetic variants were determined by spatial constraints and resulted from an efficient packing of the cochlear duct within the petrous bone. The analytical model predicts well the individual 3D cochlear geometry from few clinical measures and represents a clinical tool for an individualized approach to neurosensory restoration with cochlear implants.


Assuntos
Ducto Coclear/anatomia & histologia , Modelos Estatísticos , Osso Petroso/anatomia & histologia , Gânglio Espiral da Cóclea/anatomia & histologia , Lâmina Espiral/anatomia & histologia , Ligamento Espiral da Cóclea/anatomia & histologia , Exoesqueleto/anatomia & histologia , Exoesqueleto/ultraestrutura , Animais , Autopsia , Variação Biológica Individual , Ducto Coclear/fisiologia , Ducto Coclear/ultraestrutura , Audição/fisiologia , Humanos , Imageamento Tridimensional/instrumentação , Imageamento Tridimensional/métodos , Modelos Anatômicos , Nautilus/anatomia & histologia , Nautilus/ultraestrutura , Osso Petroso/fisiologia , Gânglio Espiral da Cóclea/fisiologia , Gânglio Espiral da Cóclea/ultraestrutura , Lâmina Espiral/fisiologia , Lâmina Espiral/ultraestrutura , Ligamento Espiral da Cóclea/fisiologia , Ligamento Espiral da Cóclea/ultraestrutura
12.
Neurotox Res ; 31(3): 348-357, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-28005182

RESUMO

The spiral ganglion neurons (SGNs) located in the Rosenthal's canal of cochlea are essential target for cochlear implant. Previous studies found that the canaliculi perforantes, small pores on the surface of the osseous spiral lamina (OSL) of the scala tympanic (ST) of cochlea, may provide communication between the cochlear perilymph and SGNs. In this study, we found that chronic treatment of aminoglycosides antibiotics, which is well known to cause sensory cell damage in the cochlea, induced significant damage of bone lining cells on the OSLs and increased the permeability of the Rosenthal's canal. The pores among the bone lining cells became significantly wider after chronic treatment of amikacin (100 mg/kg/day for 3-7 days). Injection of Evans Blue in the ST resulted in significant increase in its migration in the modulus in the amikacin-treated cochlea compared to the control ears, suggesting increased permeability of these passages. Treatment of amikacin with oxytetracycline, an inhibitor of matrix metalloproteases (MMPs), significantly reduced the amount of dye migrated from the ST to the modiolus. These results suggest that amikacin enhanced the permeability between the ST and SGNs by increasing MMPs. Aggregating the permeability of the bone lining cells on the OSLs may benefit gene and stem cell delivery to the SGNs in the cochlea.


Assuntos
Amicacina/efeitos adversos , Aminoglicosídeos/efeitos adversos , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Osteócitos/efeitos dos fármacos , Permeabilidade/efeitos dos fármacos , Lâmina Espiral/efeitos dos fármacos , Amicacina/antagonistas & inibidores , Animais , Azul Evans/metabolismo , Metaloproteinase 2 da Matriz/efeitos dos fármacos , Metaloproteinase 9 da Matriz/efeitos dos fármacos , Inibidores de Metaloproteinases de Matriz/farmacologia , Oxitetraciclina/farmacologia , Ratos , Rampa do Tímpano/metabolismo , Gânglio Espiral da Cóclea/efeitos dos fármacos , Lâmina Espiral/metabolismo
13.
J Neurosci ; 36(7): 2111-8, 2016 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-26888923

RESUMO

Auditory nerve excitation and thus hearing depend on spike-generating ion channels and their placement along the axons of auditory nerve fibers (ANFs). The developmental expression patterns and native axonal locations of voltage-gated ion channels in ANFs are unknown. Therefore, we examined the development of heminodes and nodes of Ranvier in the peripheral axons of type I ANFs in the rat cochlea with immunohistochemistry and confocal microscopy. Nodal structures presumably supporting presensory spiking formed between postnatal days 5 (P5) and P7, including Ankyrin-G, NaV1.6, and Caspr. These immature nodal structures lacked low-voltage-activated KV1.1 which was not enriched at juxtaparanodes until approximately P13, concurrent with the developmental onset of acoustic hearing function. Anatomical alignment of ANF spike-initiating heminodes relative to excitatory input from inner hair cell (IHC) ribbon synapses continued until approximately P30. High-voltage-activated KV3.1b and KV2.2 were expressed in mutually exclusive domains: KV3.1b was strictly localized to nodes and heminodes, whereas KV2.2 expression began at the juxtaparanodes and continued centrally along the first internode. At spike-initiating heminodes in the distal osseous spiral lamina, NaV1.1 partly overlapped NaV1.6 and ankyrin-G. ANFs displayed KV7.2 and KV7.3 at heminodes, nodes, internodes, and the unmyelinated synaptic terminal segments beneath IHCs in the organ of Corti. In response to sound, spikes are initiated at the heminode, which is tightly coupled to the IHC ribbon synapse ∼20-40 µm away. These results show that maturation of nodal alignment and ion channel content may underlie postnatal improvements of ANF excitability and discharge synchrony. SIGNIFICANCE STATEMENT: Acoustic and electrical hearing depends on rapid, reliable, and precise spike generation in auditory nerve fibers. A limitation of current models and therapies is a lack of information on the identities and topographies of underlying ion channels. We report the developmental profile of the auditory nerve spike generator with a focus on NaV1.1, NaV1.6, KV1.1, KV2.2, KV3.1b, KV7.2, and KV7.3 in relation to the scaffold ankyrin-G. Molecular anatomy of the spike generator matures in the weeks after developmental onset of hearing function. Subcellular positioning of voltage-gated ion channels will enable multicompartmental modeling of auditory nerve responses elicited by afferent chemical neurotransmission from hair cells and modulated by efferent neurotransmitters or evoked by extracellular field stimulation from a cochlear implant.


Assuntos
Nervo Coclear/fisiologia , Audição/fisiologia , Canais de Potássio/fisiologia , Canais de Sódio/fisiologia , Animais , Anquirinas/genética , Axônios/fisiologia , Cóclea/citologia , Cóclea/crescimento & desenvolvimento , Cóclea/fisiologia , Nervo Coclear/crescimento & desenvolvimento , Feminino , Células Ciliadas Auditivas Internas/fisiologia , Masculino , Fibras Nervosas/fisiologia , Órgão Espiral/crescimento & desenvolvimento , Órgão Espiral/fisiologia , Terminações Pré-Sinápticas/fisiologia , Nós Neurofibrosos/fisiologia , Ratos , Ratos Wistar , Lâmina Espiral/crescimento & desenvolvimento , Lâmina Espiral/fisiologia , Sinapses/fisiologia
14.
Otol Neurotol ; 33(6): 1027-33, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22805103

RESUMO

OBJECTIVE: To develop a transmastoid-posterior tympanotomy approach for the implantation of a penetrating auditory prosthesis in the most distal portion of the cochlear nerve. BACKGROUND: Animal studies suggest that penetrating cochlear nerve implants may overcome limitations of current cochlear implant systems. One step toward human implantation is the development of a suitable surgical approach. METHODS: In computer-rendered 3-dimensional (3-D) models (based on micro-CT scans of 10 human temporal bones), we simulated trajectories through the most basal part of the cochlea that gave access to the most distal portion of the cochlear nerve with minimal damage to intracochlear structures. We determined their vectors with respect to the mid-modiolar axis and posterior round window edge and assessed if they intersected the chorda tympani nerve. RESULTS: The typical vector obtained with these 3-D models ran in an anterosuperior direction, through the inferior part of the facial recess and anterior round window edge. In 7 of 10 temporal bones, this trajectory intersected the chorda tympani nerve. Based on the vectors, dummy probes were implanted in 3 of 10 temporal bones, and the need for chorda tympani removal was confirmed in accordance with the 3-D models. Postoperative micro-CT scans revealed that all probes were successfully implanted in the cochlear nerve, whereas the osseous spiral lamina and basilar membrane were preserved. CONCLUSION: The vector for drilling and implantation found in this study can be used as a guideline for real-life surgery and, therefore, is another step toward the clinical implementation of cochlear nerve implants.


Assuntos
Implante Coclear/métodos , Nervo Coclear/cirurgia , Próteses Neurais , Osso Temporal/cirurgia , Membrana Basilar/patologia , Cadáver , Nervo da Corda do Tímpano/anatomia & histologia , Cóclea/diagnóstico por imagem , Cóclea/patologia , Cóclea/cirurgia , Nervo Coclear/diagnóstico por imagem , Humanos , Modelos Anatômicos , Planejamento de Assistência ao Paciente , Tomografia por Emissão de Pósitrons , Lâmina Espiral/anatomia & histologia , Osso Temporal/diagnóstico por imagem , Microtomografia por Raio-X
15.
Auris Nasus Larynx ; 39(1): 18-24, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21601398

RESUMO

OBJECTIVE: The aim of this study is to analyse the expression and distribution of myelin basic protein (MBP or Myelin A1 protein) in the human spiral ganglion and auditory nerve. MATERIALS AND METHODS: Cryostat sections were made from freshly fixed human cochlear specimens removed at surgery in patients with life-threatening petro-clival meningiomas compressing the brain stem. The sections were subjected to immunohistochemistry using antibodies against MBP, S-100 and Tubulin. The immunoreaction was documented using laser confocal microscopy. RESULTS: Type I spiral ganglion nerve somata (SGN) were surrounded by so-called "satellite glial cells" (SGCs) that lacked expression of MBP consistent with earlier light and electron microscopic findings indicating that these cells are non-myelinating. S-100 labeling showed that the SGCs form a continuous network in the apical region. CONCLUSIONS: The pattern of myelination in human spiral ganglion is different from that in other species' spiral ganglion. The striking differences in myelin outline should be investigated further in combination with its influence on signal coding and preservation properties in man.


Assuntos
Nervo Coclear/metabolismo , Proteína Básica da Mielina/metabolismo , Gânglio Espiral da Cóclea/metabolismo , Lâmina Espiral/metabolismo , Adulto , Animais , Nervo Coclear/ultraestrutura , Feminino , Cobaias , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Proteínas S100/metabolismo , Gânglio Espiral da Cóclea/ultraestrutura , Lâmina Espiral/ultraestrutura , Suínos , Tubulina (Proteína)/metabolismo
16.
Surg Radiol Anat ; 34(8): 781-5, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22120898

RESUMO

PURPOSE: To define the rotational anatomy of the osseous spiral lamina (OSL) at the hook region and along the basal turn of the cochlea and to illustrate the potential utility of high-resolution MRI images to study inner ear ultrastructure. METHODS: Retrospective review of high-resolution temporal bone MRI images in 20 consecutive adult patients referred for imaging unrelated to hearing loss. The main outcome measure utilised images in an oblique sagittal plane to measure the rotation of the OSL relative to the vertical axis in the hook region and along the basal turn of the cochlea. RESULTS: The right OSL is noted to rotate in a clockwise direction as one proceeds anteriorly; over the same distance, the left OSL rotates in an anti-clockwise direction. The average overall rotation for all subjects as measured over a distance of 1-7 mm from the posterior margin of the round window was 25.95°. Inter-subject variability was noted. CONCLUSIONS: Prominent rotation of the OSL was noted in the hook region, this being most pronounced in the proximity to the round window. This concept may have implications for cochleostomy site selection with implant surgery. The study highlights the feasibility of high-resolution MRI to be used to systematically study variations in intra-cochlear anatomy.


Assuntos
Imageamento por Ressonância Magnética/métodos , Lâmina Espiral/anatomia & histologia , Adulto , Idoso , Cóclea/anatomia & histologia , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Osso Temporal/anatomia & histologia , Adulto Jovem
17.
Acta Otolaryngol ; 130(3): 358-65, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19685360

RESUMO

CONCLUSION: Changes in the metabolism of arachidonic acid (AA) might be part of a noise-induced compensatory mechanism with regional specificity. OBJECTIVES: The released imbalance of prostaglandins and leukotrienes, both AA metabolites, might result in altered blood flow regulation in the inner ear and probably contributes to noise-induced hearing loss. The aim of this study was to gain further information about noise-dependent changes in AA metabolism in the mammalian cochlea. METHODS: In this prospective animal study, 10 male guinea pigs were exposed to tone bursts for 1 h at 70 dB sound pressure level (SPL) (n = 5) or 90 dB SPL (n = 5). Five animals were used as controls. Alterations in cyclooxygenase 1 (COX-1) and 5-lipoxygenase (5-LO) expression were determined by quantitative immunohistochemical analysis in 11 cochlear regions. RESULTS: COX-1 expression was decreased after both 70 dB SPL and 90 dB SPL exposure in most cell types of the organ of Corti and increased in the nerve fibers of the osseous spiral lamina. 5-LO was lowered after 90 dB SPL exposure, preferentially in the third cochlear turn in the organ of Corti, in the first and second turn in spiral ganglion cells, and in all turns in the stria vascularis.


Assuntos
Araquidonato 5-Lipoxigenase/metabolismo , Cóclea/patologia , Ciclo-Oxigenase 1/metabolismo , Perda Auditiva Provocada por Ruído/patologia , Animais , Ácido Araquidônico/metabolismo , Regulação para Baixo/fisiologia , Cobaias , Humanos , Técnicas Imunoenzimáticas , Masculino , Fibras Nervosas/patologia , Órgão Espiral/patologia , Estudos Prospectivos , Células de Schwann/patologia , Gânglio Espiral da Cóclea/patologia , Lâmina Espiral/patologia , Ligamento Espiral da Cóclea/patologia , Estria Vascular/patologia , Regulação para Cima/fisiologia
19.
Acta Otolaryngol ; 130(4): 443-52, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19883180

RESUMO

CONCLUSION: Cochlear implantation assessment is possible using commercially available standard flat-detector computed tomography (FD-CT) protocols. Image quality is superior to multislice CT (MSCT). The radiation dose of FD-CT is lower in comparison with MSCT standard protocols and may therefore overcome the limitations of MSCT in the evaluation of cochlear implants. OBJECTIVE: FD-CT offers higher spatial resolution than MSCT. Our objective was to compare the image quality of FD-CT to conventional MSCT in the visualization of a cochlear implant electrode array with respect to radiation exposure. METHODS: An isolated temporal bone specimen was scanned using a commercially available FD-CT system and a 4 and 64 row MSCT scanner. Different scanning protocols were used. Image quality was assessed by four independent readers using a scoring system with different criteria describing delineation of the cochlea and the electrode array, image noise and spatial resolution. Radiation dose was measured using the CT dose index (CTDI) and a 16 cm acrylic phantom. RESULTS: Image quality was rated superior for FD-CT for all criteria by all readers. Single electrode contacts were only visible in FD-CT and assessment of implant position was improved by FD-CT. The radiation dose of FD-CT was half that of MSCT standard protocols.


Assuntos
Cóclea/diagnóstico por imagem , Implantes Cocleares , Aumento da Imagem/instrumentação , Osso Temporal/diagnóstico por imagem , Tomografia Computadorizada por Raios X/instrumentação , Artefatos , Estimulação Elétrica/métodos , Eletrodos Implantados , Desenho de Equipamento , Nervo Facial/diagnóstico por imagem , Transtornos da Audição/terapia , Humanos , Processo Mastoide/diagnóstico por imagem , Processo Mastoide/cirurgia , Período Pós-Operatório , Doses de Radiação , Lâmina Espiral/diagnóstico por imagem , Membrana Timpânica/diagnóstico por imagem , Membrana Timpânica/cirurgia
20.
J Acoust Soc Am ; 123(4): 2160-71, 2008 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-18397023

RESUMO

In this paper, two sets of experimental results to extract the two effective elastic moduli, the effective shear modulus, and the effective Poisson's ratio for the gerbil cochlear partition are analyzed. In order to accomplish this, a geometrically nonlinear composite orthotropic plate model is employed. The model is used to predict both out-of-plane and in-plane motion of the partition under a static finite area distributed load. This loading condition models the small, but finite size, probe tips used in experiments. Both in-plane and out-of-plane motion are needed for comparison with recent experimental results. It is shown that the spatial decay rate (the space constant) for the in-plane deflection is different than for the out-of-plane deflection, which has a significant effect on the derived partition properties. The size of the probe tip is shown to have little influence on the results. Results are presented for two types of boundary conditions. Orthotropy ratios determined from the experimental data are found to vary with longitudinal position and choice of boundary conditions. Orthotropy ratios (the ratio of the two elastic moduli) are in the range of 65 close to the base to 10 in the upper middle turn of the cochlea.


Assuntos
Membrana Basilar/fisiologia , Cóclea/fisiologia , Modelos Teóricos , Animais , Elasticidade , Gerbillinae , Lâmina Espiral/fisiologia
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