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| 2. |
- Chacko, L. Johnson, et al.
(författare)
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Role of BDNF and neurotrophic receptors in human inner ear development
- 2017
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Ingår i: Cell and Tissue Research. - : SPRINGER. - 0302-766X .- 1432-0878. ; 370:3, s. 347-363
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Tidskriftsartikel (refereegranskat)abstract
- The expression patterns of the neurotrophin, brain-derived neurotrophic factor, BDNF, and the neurotrophic receptors-p75NTR and Trk receptors-in the developing human fetal inner ear between the gestational weeks (GW) 9 to 12 are examined via in situ hybridization and immunohistochemistry. BDNF mRNA expression was highest in the cochlea at GW 9 but declined in the course of development. In contrast to embryonic murine specimens, a decline in BDNF expression from the apical to the basal turn of the cochlea could not be observed. p75NTR immunostaining was most prominent in the nerve fibers that penetrate into the sensory epithelia of the cochlea, the urticule and the saccule as gestational age progresses. TrkB and TrkC expression intensified towards GW 12, at which point the BDNF mRNA localization was at its lowest. TrkA expression was limited to fiber subpopulations of the facial nerve at GW 10. In the adult human inner ear, we observed BDNF mRNA expression in the apical poles of the cochlear hair cells and supporting cells, while in the adult human utricle, the expression was localized in the vestibular hair cells. We demonstrate the highly specific staining patterns of BDNF mRNA and its putative receptors over a developmental period in which multiple hearing disorders are manifested. Our findings suggest that BDNF and neurotrophin receptors are important players during early human inner ear development. In particular, they seem to be important for the survival of the afferent sensory neurons.
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| 3. |
- Glueckert, R., et al.
(författare)
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Anatomical basis of drug delivery to the inner ear
- 2018
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Ingår i: Hearing Research. - : Elsevier. - 0378-5955 .- 1878-5891. ; 368, s. 10-27
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Forskningsöversikt (refereegranskat)abstract
- The isolated anatomical position and blood-labyrinth barrier hampers systemic drug delivery to the mammalian inner ear. Intratympanic placement of drugs and permeation via the round-and oval window are established methods for local pharmaceutical treatment. Mechanisms of drug uptake and pathways for distribution within the inner ear are hard to predict. The complex microanatomy with fluid filled spaces separated by tight-and leaky barriers compose various compartments that connect via active and passive transport mechanisms. Here we provide a review on the inner ear architecture at light-and electron microscopy level, relevant for drug delivery. Focus is laid on the human inner ear architecture. Some new data add information on the human inner ear fluid spaces generated with high resolution microcomputed tomography at 15 urn resolution. Perilymphatic spaces are connected with the central modiolus by active transport mechanisms of mesothelial cells that provide access to spiral ganglion neurons. Reports on leaky barriers between scala tympani and the so-called cortilymph compartment likely open the best path for hair cell targeting. The complex barrier system of tight junction proteins such as occludins, claudins and tricellulin isolates the endolymphatic space for most drugs. Comparison of relevant differences of barriers, target cells and cell types involved in drug spread between main animal models and humans shall provide some translational aspects for inner ear drug applications. (C) 2018 The Authors. Published by Elsevier B.V.
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| 5. |
- Glueckert, Rudolf, et al.
(författare)
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Histology and synchrotron radiation-based microtomography of the inner ear in a molecularly confirmed case of CHARGE syndrome
- 2010
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Ingår i: American journal of medical genetics. Part A. - : Wiley. - 1552-4825 .- 1552-4833. ; 152A:3, s. 665-673
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Tidskriftsartikel (refereegranskat)abstract
- CHARGE (Coloboma of the iris or retina, heart defects, atresia of the choanae, retardation of growth and/or development, genital anomalies, ear anomalies) syndrome (OMIM #214800) affects about 1 in 10,000 children and is most often caused by chromodomain helicase DNA-binding protein-7 (CHD7) mutations. Inner ear defects and vestibular abnormalities are particularly common. Specifically, semicircular canal (SCC) hypoplasia/aplasia and the presence of a Mondini malformation can be considered pathognomonic in the context of congenital malformations of the CHARGE syndrome. We obtained a temporal bone (TB) of a patient with CHARGE syndrome who died from bacteremia at 3 months of age. The clinical diagnosis was confirmed in the patient by direct DNA sequencing and the detection of a de novo, truncating CHD7 mutation, c.6169dup (p.R2057fs). We assessed changes of the TB and the degree of neural preservation, which may influence the potential benefit of cochlear implantation. The TB was analyzed using synchrotron radiation-based micro computed tomography, and by light microscopy. The vestibular partition consisted of a rudimentary vestibule with agenesis of the SCCs. The cochlea was hypoplastic with poor or deficient interscaling and shortened (Mondini dysplasia). The organ of Corti had near normal structure and innervation. Modiolus and Rosenthal's canal were hypoplastic with perikarya displaced along the axon bundles into the internal acoustic meatus, which may be explained by the arrest or limited migration and translocation of the cell nuclei into the cochlear tube during development.
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| 6. |
- Liu, Wei, et al.
(författare)
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Super-resolution structured illumination fluorescence microscopy of the lateral wall of the cochlea : the Connexin26/30 proteins are separately expressed in man
- 2016
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Ingår i: Cell and Tissue Research. - : Springer. - 0302-766X .- 1432-0878. ; , s. 1-15
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 7. |
- Liu, Wei, et al.
(författare)
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The Pre- and Post-Somatic Segments of the Human Type I Spiral Ganglion Neurons - Structural and Functional Considerations Related to Cochlear Implantation
- 2015
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Ingår i: Neuroscience. - : Elsevier BV. - 0306-4522 .- 1873-7544. ; 284, s. 470-482
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Tidskriftsartikel (refereegranskat)abstract
- Human auditory nerve afferents consist of two separate systems; one is represented by the large type I cells innervating the inner hair cells and the other one by the small type II cells innervating the outer hair cells. Type I spiral ganglion neurons (SGNs) constitute 96% of the afferent nerve population and, in contrast to other mammals, their soma and pre- and post-somatic segments are unmyelinated. Type II nerve soma and fibers are unmyelinated. Histopathology and clinical experience imply that human SGNs can persist electrically excitable without dendrites, thus lacking connection to the organ of Corti. The biological background to this phenomenon remains elusive. We analyzed the pre- and post-somatic segments of the type I human SGNs using immunohistochemistry and transmission electron microscopy (TEM) in normal and pathological conditions. These segments were found surrounded by non-myelinated Schwann cells (NMSCs) showing strong intracellular expression of laminin-beta 2/collagen IV. These cells also bordered the perikaryal entry zone and disclosed surface rugosities outlined by a folded basement membrane (BM) expressing laminin-beta 2 and collagen IV. It is presumed that human large SGNs are demarcated by three cell categories: (a) myelinated Schwann cells, (b) NMSCs and (c) satellite glial cells (SGCs). Their BMs express laminin-beta 2/collagen IV and reaches the BM of the sensory epithelium at the habenula perforata. We speculate that the NMSCs protect SGNs from further degeneration following dendrite loss. It may give further explanation why SGNs can persist as electrically excitable monopolar cells even after long-time deafness, a blessing for the deaf treated with cochlear implantation. (C) 2014 The Authors. Published by Elsevier Ltd. on behalf of IBRO. This is an open access article under the CC BY-NC-ND license.
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| 8. |
- Rask-Andersen, Helge, et al.
(författare)
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Human cochlea : Anatomical characteristics and their relevance for cochlear implantation
- 2012
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Ingår i: Anatomical Record. - : Wiley. - 1932-8486. ; 295:11, s. 1791-1811
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Tidskriftsartikel (refereegranskat)abstract
- This is a review of the anatomical characteristics of human cochlea and the importance of variations in this anatomy to the process of cochlear implantation (CI). Studies of the human cochlea are essential to better comprehend the physiology and pathology of man's hearing. The human cochlea is difficult to explore due to its vulnerability and bordering capsule. Inner ear tissue undergoes quick autolytic changes making investigations of autopsy material difficult, even though excellent results have been presented over time. Important issues today are novel inner ear therapies including CI and new approaches for inner ear pharmacological treatments. Inner ear surgery is now a reality, and technical advancements in the design of electrode arrays and surgical approaches allow preservation of remaining structure/function in most cases. Surgeons should aim to conserve cochlear structures for future potential stem cell and gene therapies. Renewal interest of round window approaches necessitates further acquaintance of this complex anatomy and its variations. Rough cochleostomy drilling at the intricate "hook" region can generate intracochlear bone-dust-inducing fibrosis and new bone formation, which could negatively influence auditory nerve responses at a later time point. Here, we present macro- and microanatomic investigations of the human cochlea viewing the extensive anatomic variations that influence electrode insertion. In addition, electron microscopic (TEM and SEM) and immunohistochemical results, based on specimens removed at surgeries for life-threatening petroclival meningioma and some well-preserved postmortal tissues, are displayed. These give us new information about structure as well as protein and molecular expression in man. Our aim was not to formulate a complete description of the complex human anatomy but to focus on aspects clinically relevant for electric stimulation, predominantly, the sensory targets, and how surgical atraumaticity best could be reached.
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| 9. |
- Rask-Andersen, Helge, et al.
(författare)
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Immunolocalization of prestin in human Cochlea
- 2010
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Ingår i: Audiological Medicine. - : Informa UK Limited. - 1651-386X .- 1651-3835. ; 8:2, s. 56-62
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Prestin is an anion-transporter-related protein highly expressed in mammalian outer hair cells (OHCs). It is associatedwith the OHC basolateral plasma membrane and responsible for cell body contraction, increasing cochlear sensitivityand frequency resolution. Here, we analysed the expression and distribution of prestin in the human cochlea. Study Design:Immunohistochemistry including confocal microscopy and SEM were performed on EDTA-decalcifi ed human cochlearemoved during petro-clival meningioma surgery. Results: Prestin was found to be expressed solely in OHCs. No stainingwas seen in IHCs. Prestin immunolabelling framed the OHCs along the sensory region of the human cochlea. Staining wasmost prominent in the lateral cell membrane with less expression in the sub- and peri-nuclear part of the cell. Prestin immunostainingwas also detected in the OHC cytosol, presumably refl ecting intracellular molecular traffi cking. Conclusion: Thisstudy describes for the fi rst time the localization and distribution of prestin in the well preserved human organ of Corti.
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| 10. |
- Schrott-Fischer, A., et al.
(författare)
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Efferent neurotransmitters in the human cochlea and vestibule
- 2007
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Ingår i: Acta Oto-Laryngologica. - : Informa UK Limited. - 0001-6489 .- 1651-2251. ; 127:1, s. 13-19
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Tidskriftsartikel (refereegranskat)abstract
- Conclusion: Current neurotransmission models based on animal studies on the mammalian inner ear not always reflect the situation in human. Rodents and primates show significant differences in characteristics of efferent innervation as well as the distribution of neuroactive substances. Objective: Immunohistochemistry demonstrates the mammalian efferent system as neurochemically complex and diverse: several neuroactive substances may co-exist within the same efferent terminal. Using light and electron microscopic immunohistochemistry, this study presents a comparative overview of the distribution patterns of choline acetyltransferase (ChAT), the acetylcholine synthesizing enzyme, GABA, CGRP, and enkephalins within the peripheral nerve fiber systems of the human inner ear. Materials and methods: Human temporal bones were obtained post mortem and prepared according to a pre-embedding immunohistochemical technique to detect immunoreactivities to ChAT, GABA, CGRP, leu- and met-enkephalins at the electron microscopic level. Results: Immunoreactivities of all the antigens were present within both the lateral and medial efferent systems of the cochlea, whereas only ChAT, GABA, and CGRP were detected in efferent pathways of the vestibular end organs.
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