1,721,143 research outputs found
Internalization of nanoparticles into spiral ganglion cells
No full textThe delivery of drugs or genes to the inner ear in a controlled and biocompatible manner could lead to new treatmentsfor conditions such as Ménière’s disease, tinnitus, schwannomas of the ear, and for improving hearing.The concept of multifunctional nanoparticles, which are targetable, biodegradable, and traceable, has led to newapproaches to controlled drug release and localized delivery to specific cell populations. Tissue-specific deliverycan be achieved by functionally “addressed” nanostructures loaded with a therapeutic molecule. In the presentstudy, we investigated the incorporation, distribution, and toxicology of amphiphilic block copolymer nanoparticles(NPs) in spiral ganglion (SG) cell cultures. Adult human and guinea pig SG neurons and glia/Schwanndissociated cell cultures were expanded, grown for several weeks, and then studied live using time-lapse videomicroscopy and high-resolution light microscopy. The cells were further characterized using immunocytochemistryfor the neural marker TuJ1 and the glia cell markers S-100 and GFAP, and their morphology was studiedin more detail using scanning electron microscopy (SEM). These cell cultures were exposed to fluorescently(Dil)-loaded NPs for different time periods and at different concentrations, and the uptake was studied usingfluorescence microscopy. The study demonstrates that DiI-loaded NPs can be internalized into guinea pig SGneurons as well as into human and guinea pig SG glia/Schwann cells without indication of toxicity or reducedviability. After 4 hours, almost 100% of both the neurons and the glia cells had incorporated the NPs into thecytoplasm. No uptake could be detected in the nucleus and no evidence of internalization could be seen inaxons or in the growth cone area of the neuron. Especially in the glia cells, the NPs were detected in smallvesicles surrounding the nucleus and occasionally in the periphery of the cytoplasm. This information could leadto the development of more specialized NPs, targeting only SG neurons or Schwann cells
The human cochlear aqueduct and accessory canals: a micro-CT analysis using a 3D reconstruction paradigm
No full textObjective: We sought to study the anatomic variations of the cochlear aqueduct and its accessory canals in human temporal bones using micro-CT and a 3D reconstruction paradigm. More knowledge about the anatomic variations of these structures, particularly at the basal turn of the cochlea and round window niche, may be important to better preserve residual hearing as well as the neural supply during cochlear implant surgery. Methods: An archival collection of 30 human temporal bones underwent micro-CT and 3D reconstruction. A surface enhancement paradigm was applied. The application displays reconstructed slices as a 3D object with realistic 3D visualization of scanned objects. Virtual sectioning or "cropping" of the petrous bone presented subsequent areas. Thereby, the bony canals could be followed from inside the basal turn of cochlea and middle ear to the jugular foramen. Results: The cochlear aqueduct was always paralleled by an accessory canal containing the inferior cochlear vein. It ran from the basal turn of the cochlea and exited laterally in the jugular foramen. In 70% of the cases, a secondary accessory canal was observed and it derived mostly from a depression or infundibulum located in the floor of the round window niche. This canal also exited in the jugular foramen. The secondary accessory canal occasionally anastomosed with the primary accessory canal suggesting that it contains a vein that drains middle ear blood to the cranial sinus. Conclusion: Micro-CT with 3D surface reconstruction paradigm offers new possibilities to study the topographic anatomy of minor details in the human inner ear. The technique creates simulated transparent "castings" of the labyrinth with a coinciding surface view through enhancement of contrast between boundaries. Accessory canals that drain blood from the cochlea, spiral ganglion, and middle ear could be characterized three-dimensionally
Human inner ear blood supply revisited : the Uppsala collection of temporal bone - an international resource of education and collaboration
Full text linkBackground: The Uppsala collection of human temporal bones and molds is a unique resource for education and international research collaboration. Micro-computerized tomography (micro-CT) and synchrotron imaging are used to investigate the complex anatomy of the inner ear. Impaired microcirculation is etiologically linked to various inner ear disorders, and recent developments in inner ear surgery promote examination of the vascular system. Here, for the first time, we present three-dimensional (3D) data from investigations of the major vascular pathways and corresponding bone channels. Methods: We used the archival Uppsala collection of temporal bones and molds consisting of 324 inner ear casts and 113 macerated temporal bones. Micro-CT was used to investigate vascular bone channels, and 26 fresh human temporal bones underwent synchrotron radiation phase contrast imaging (SR-PCI). Data were processed by volume-rendering software to create 3D reconstructions allowing orthogonal sectioning, cropping, and soft tissue analyses. Results: Micro-CT with 3D rendering was superior in reproducing the anatomy of the vascular bone channels, while SR-PCI replicated soft tissues. Arterial bone channels were traced from scala vestibuli (SV) arterioles to the fundus, cochlea, and vestibular apparatus. Drainage routes along the aqueducts were examined. Conclusion: Human inner ear vessels are difficult to study due to the adjoining hard bone. Micro-CT and SR-PCI with 3D reconstructions revealed large portions of the micro-vascular system in un-decalcified specimens. The results increase our understanding of the organization of the vascular system in humans and how altered microcirculation may relate to inner ear disorders. The findings may also have surgical implications
Na/K-ATPase Gene Expression in the Human Cochlea : A Study Using mRNA in situ Hybridization and Super-Resolution Structured Illumination Microscopy
No full textBackground: The pervasive Na/K-ATPase pump is highly expressed in the human cochlea and is involved in the generation of the endocochlear potential as well as auditory nerve signaling and relay. Its distribution, molecular organization and gene regulation are essential to establish to better understand inner ear function and disease. Here, we analyzed the expression and distribution of the ATP1A1, ATP1B1, and ATP1A3 gene transcripts encoding the Na/K-ATPase alpha 1, alpha 3, and beta 1 isoforms in different domains of the human cochlea using RNA in situ hybridization. Materials and Methods: Archival paraformaldehyde-fixed sections derived from surgically obtained human cochleae were used to label single mRNA gene transcripts using the highly sensitive multiplex RNAscope (R) technique. Localization of gene transcripts was performed by super-resolution structured illumination microscopy (SR-SIM) using fluorescent-tagged probes. GJB6 encoding of the protein connexin30 served as an additional control. Results: Single mRNA gene transcripts were seen as brightly stained puncta. Positive and negative controls verified the specificity of the labeling. ATP1A1 and ATP1B1 gene transcripts were demonstrated in the organ of Corti, including the hair and supporting cells. In the stria vascularis, these transcripts were solely expressed in the marginal cells. A large number of ATP1B1 gene transcripts were found in the spiral ganglion cell soma, outer sulcus, root cells, and type II fibrocytes. The ATP1B1 and ATP1A3 gene transcripts were rarely detected in axons. Discussion: Surgically obtained inner ear tissue can be used to identify single mRNA gene transcripts using high-resolution fluorescence microscopy after prompt formaldehyde fixation and chelate decalcification. A large number of Na/K-ATPase gene transcripts were localized in selected areas of the cochlear wall epithelium, fibrocyte networks, and spiral ganglion, confirming the enzyme's essential role for human cochlear function
Auditory brainstem implant pitch discrimination and auditory outcome
No full textWe present a pitch discrimination test performed by five experienced adult auditory brainstem implant (ABI) users with neurofibromatosis type 2 (NF2). The ability to discriminate frequency/pitch from different channels on the implant may be an important factor in improving speech performance. The pitch discrimination ability was evaluated by using a triangle test compared to adjacent contacts and the speech perception was measured by the Swedish three-digit test. The test was easy to perform, and all patients were able to answer reliably, even though it cannot be ruled out that patients used attributes other than pitch to differentiate between sounds. Due to the limited number of patients and small variation in results, no conclusive correlations could be made regarding pitch discrimination and auditory outcome. There was a tendency for poorer ability to discriminate pitch (discrimination of tonotopically adjacent electrodes) at testing to result in poorer speech results
GJB2 and GJB6 gene transcripts in the human cochlea : A study using RNAscope, confocal, and super-resolution structured illumination microscopy
No full textBackground: Gap junction (GJ) proteins, connexin26 and 30, are highly prevalent in the human cochlea (HC), where they are involved in transcellular signaling, metabolic supply, and fluid homeostasis. Their genes, GJB2 and GJB6, are both located at the DFNB1 locus on chromosome 13q12. Mutations in GJB2 may cause mild to profound non-syndromic deafness. Here, we analyzed for the first time the various expressions of GJB2 and GJB6 gene transcripts in the different cell networks in the HC using the RNAscope technique. Materials and methods: Archival paraformaldehyde-fixed sections of surgically obtained HC were used to label single mRNA oligonucleotides using the sensitive multiplex RNAscope (R) technique with fluorescent-tagged probes. Positive and negative controls also included the localization of ATP1A1, ATP1A2, and KCNJ10 gene transcripts in order to validate the specificity of labeling. Results: Confocal and super-resolution structured illumination microscopy (SR-SIM) detected single gene transcripts as brightly stained puncta. The GJB2 and GJB6 gene transcripts were distributed in the epithelial and connective tissue systems in all three cochlear turns. The largest number of GJB2 and GJB6 gene transcripts was in the outer sulcus, spiral ligament, and stria vascularis (SV). Oligonucleotides were present in the supporting cells of the organ of Corti (OC), spiral limbus fibrocytes, and the floor of the scala vestibuli. Multiplex gene data suggest that cells in the cochlear lateral wall contain either GJB2 or GJB6 gene transcripts or both. The GJB6, but not GJB2, gene transcripts were found in the intermediate cells but none were found in the marginal cells. There were no GJB2 or GJB6 gene transcripts found in the hair cells and only a few in the spiral ganglion cells. Conclusion: Both GJB2 and GJB6 mRNA gene transcripts were localized in cells in the adult HC using RNAscope (R) in situ hybridization (ISH) and high resolution microscopy. Generally, GJB6 dominated over GJB2, except in the basal cells. Results suggest that cells may contain either GJB2 or GJB6 gene transcripts or both. This may be consistent with specialized GJ plaques having separate channel permeability and gating properties. A reduction in the number of GJB2 gene transcripts was found in the basal turn. Such information may be useful for future gene therapy
How to predict cochlear length before cochlear implantation surgery
No full textConclusions: The basal turn diameter of the human cochlea predicts the outer wall length of the basal and two first turns relatively well but there was less correlation for the total cochlear length. The linear regression graph defines the length of the basal turn within an error of +/- 1 mm and could be used clinically to distinguish small and large cochleae. Objective: The human cochlea varies in size. The preoperative assessment of cochlear length can be crucial for non-traumatic electrode insertion and hearing preservation. In this study, we estimated the external cochlear wall length by assessing the basal turn diameter. Methods: A total of 51 non-selected, human inner ear moulds were analysed. A line was drawn from the midpoint of the round window through the cochlear mid-portion to the opposite side (A) and correlated to the cochlear turn lengths. Linear regression analyses were carried out. Results: Mean diameter A was 9.3 mm. The mean basal turn length was 22.8 mm, the two first turns were 35.1 mm and the total length was 41.2 mm. Linear regression analyses indicated a coefficient of determination (R-2) of 0.74 for diameter A and the basal turn length, R-2 = 0.70 for the two-turn length and R-2 = 0.39 for the total length.</p
Hearing and patient satisfaction in 19 patients receiving implants intended for hybrid hearing : A two-year follow-up
No full textCarotid Artery Compression Caused by the Cochlea
No full textHypothesis We investigated the possible interference between the human internal carotid artery and the cochlea. Background The cochlea and the internal carotid artery (ICA) are anatomically closely related in the human temporal bone. The intimacy may even result in functional interferences. Methods Here, we analyzed 324 human plastic inner ear corrosion casts including the ICA canal and jugular bulb. Results Results showed that in 23% (14 cases), the cochlea caused physical impression in the carotid canal (CA) with luminal restriction. In one case, there was no separation between the CC and the basal turn of the cochlea. The distance between the CC and the cochlea varied between 0 and 1 mm among these 14 specimens. The lumen restriction of the CC in the pyramid-axial projection varied between 39% and 79%. Conclusion We speculate that the reduction in ICA canal lumen size caused by the cochlea may form a predilection site for intratemporal ICA plaque formation and therefore be clinically relevant.</p
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