| 1. |
- Eckhard, Andreas, et al.
(författare)
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Co-localisation of Kir4.1 and AQP4 in rat and human cochleae reveals a gap in water channel expression at the transduction sites of endocochlear K+ recycling routes
- 2012
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Ingår i: Cell and Tissue Research. - : Springer Science and Business Media LLC. - 0302-766X .- 1432-0878. ; 350:1, s. 27-43
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Tidskriftsartikel (refereegranskat)abstract
- Sensory transduction in the cochlea depends on perilymphatic-endolymphatic potassium (K+) recycling. It has been suggested that the epithelial supporting cells (SCs) of the cochlear duct may form the intracellular K+ recycling pathway. Thus, they must be endowed with molecular mechanisms that facilitate K+ uptake and release, along with concomitant osmotically driven water movements. As yet, no molecules have been described that would allow for volume-equilibrated transepithelial K+ fluxes across the SCs. This study describes the subcellular co-localisation of the Kir4.1 K+ channel (Kir4.1) and the aquaporin-4 water channel (AQP4) in SCs, on the basis of immunohistochemical double-labelling experiments in rat and human cochleae. The results of this study reveal the expression of Kir4.1 in the basal or basolateral membranes of the SCs in the sensory domain of the organ of Corti that are adjacent to hair cells and in the non-sensory domains of the inner and outer sulci that abut large extracellular fluid spaces. The SCs of the inner sulcus (interdental cells, inner sulcus cells) and the outer sulcus (Hensen’s cells, outer sulcus cells) display the co-localisation of Kir4.1 and AQP4 expression. However, the SCs in the sensory domain of the organ of Corti reveal a gap in the expression of AQP4. The outer pillar cell is devoid of both Kir4.1 and AQP4. The subcellular co-localisation of Kir4.1 and AQP4 in the SCs of the cochlea described in this study resembles that of the astroglia of the central nervous system and the glial Mueller cells in the retina.
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| 2. |
- Eckhard, Andreas, et al.
(författare)
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Water channel proteins in the inner ear and their link to hearing impairment and deafness
- 2012
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Ingår i: Molecular Aspects of Medicine. - : Elsevier BV. - 0098-2997 .- 1872-9452. ; 33:5-6, s. 612-637
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Tidskriftsartikel (refereegranskat)abstract
- The inner ear is a fluid-filled sensory organ that transforms mechanical stimuli into the senses of hearing and balance. These neurosensory functions depend on the strict regulation of the volume of the two major extracellular fluid domains of the inner ear, the perilymph and the endolymph. Water channel proteins, or aquaporins (AQPs), are molecular candidates for the precise regulation of perilymph and endolymph volume. Eight AQP subtypes have been identified in the membranous labyrinth of the inner ear. Similar AQP subtypes are also expressed in the kidney, where they function in whole-body water regulation. In the inner ear, AQP subtypes are ubiquitously expressed in distinct cell types, suggesting that AQPs have an important physiological role in the volume regulation of perilymph and endolymph. Furthermore, disturbed AQP function may have pathophysiological relevance and may turn AQPs into therapeutic targets for the treatment of inner ear diseases. In this review, we present the currently available knowledge regarding the expression and function of AQPs in the inner ear. We give special consideration to AQP subtypes AQP2, AQP4 and AQP5, which have been studied most extensively. The potential functions of AQP2 and AQP5 in the resorption and secretion of endolymph and of AQP4 in the equilibration of cell volume are described. The pathophysiological implications of these AQP subtypes for inner ear diseases, that appear to involve impaired fluid regulation, such as Menière's disease and Sjögren's syndrome, are discussed.
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| 3. |
- Frick, Claudia, et al.
(författare)
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Age-Dependency of Neurite Outgrowth in Postnatal Mouse Cochlear Spiral Ganglion Explants
- 2020
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Ingår i: Brain Sciences. - : MDPI. - 2076-3425. ; 10:9
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Tidskriftsartikel (refereegranskat)abstract
- Background: The spatial gap between cochlear implants (CIs) and the auditory nerve limits frequency selectivity as large populations of spiral ganglion neurons (SGNs) are electrically stimulated synchronously. To improve CI performance, a possible strategy is to promote neurite outgrowth toward the CI, thereby allowing a discrete stimulation of small SGN subpopulations. Brain-derived neurotrophic factor (BDNF) is effective to stimulate neurite outgrowth from SGNs.Method: TrkB (tropomyosin receptor kinase B) agonists, BDNF, and five known small-molecule BDNF mimetics were tested for their efficacy in stimulating neurite outgrowth in postnatal SGN explants. To modulate Trk receptor-mediated effects, TrkB and TrkC ligands were scavenged by an excess of recombinant receptor proteins. The pan-Trk inhibitor K252a was used to block Trk receptor actions.Results: THF (7,8,3 '-trihydroxyflavone) partly reproduced the BDNF effect in postnatal day 7 (P7) mouse cochlear spiral ganglion explants (SGEs), but failed to show effectiveness in P4 SGEs. During the same postnatal period, spontaneous and BDNF-stimulated neurite outgrowth increased. The increased neurite outgrowth in P7 SGEs was not caused by the TrkB/TrkC ligands, BDNF and neurotrophin-3 (NT-3).Conclusions: The age-dependency of induction of neurite outgrowth in SGEs was very likely dependent on presently unidentified factors and/or molecular mechanisms which may also be decisive for the age-dependent efficacy of the small-molecule TrkB receptor agonist THF.
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| 4. |
- Frick, Claudia, et al.
(författare)
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Biofunctionalized peptide-based hydrogels provide permissive scaffolds to attract neurite outgrowth from spiral ganglion neurons
- 2017
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Ingår i: Colloids and Surfaces B. - : Elsevier BV. - 0927-7765 .- 1873-4367. ; 149, s. 105-114
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Tidskriftsartikel (refereegranskat)abstract
- Cochlear implants (CI) allow for hearing rehabilitation in patients with sensorineural hearing loss or deafness. Restricted CI performance results from the spatial gap between spiral ganglion neurons and the CI, causing current spread that limits spatially restricted stimulation and impairs frequency resolution. This may be substantially improved by guiding peripheral processes of spiral ganglion neurons towards and onto the CI electrode contacts. An injectable, peptide-based hydrogel was developed which may provide a permissive scaffold to facilitate neurite growth towards the CI. To test hydrogel capacity to attract spiral ganglion neurites, neurite outgrowth was quantified in an in vitro model using a custom-designed hydrogel scaffold and PuraMatrix(®). Neurite attachment to native hydrogels is poor, but significantly improved by incorporation of brain-derived neurotrophic factor (BDNF), covalent coupling of the bioactive laminin epitope IKVAV and the incorporation a full length laminin to hydrogel scaffolds. Incorporation of full length laminin protein into a novel custom-designed biofunctionalized hydrogel (IKVAV-GGG-SIINFEKL) allows for neurite outgrowth into the hydrogel scaffold. The study demonstrates that peptide-based hydrogels can be specifically biofunctionalized to provide a permissive scaffold to attract neurite outgrowth from spiral ganglion neurons. Such biomaterials appear suitable to bridge the spatial gap between neurons and the CI.
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| 5. |
- Rask-Andersen, Helge, et al.
(författare)
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Anatomy of the human cochlea : implications for cochlear implantation
- 2011
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Ingår i: Cochlear Implants International. - 1467-0100 .- 1754-7628. ; 12:Suppl 1, s. S8-S13
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Tidskriftsartikel (refereegranskat)abstract
- Since the classical description by Retzius in 1884, many extensive studies of the micro-anatomy of the human cochlea have been presented. The human cochlea is one of the most difficult tissues to study due to the bony capsule and its delicate contents. Most preparations suffer from post-mortem changes caused by the delay between demise and fixation. For over a decade, we have analyzed human inner-ear tissue obtained at surgery using transmission electron microscopy, scanning electron microscopy, in vitro culture, and immunohistochemistry. These studies show the value of these techniques for fine structural and molecular analyses. Modern cochlear implant surgery requires that ear surgeons are familiar with the intricate anatomy of the human cochlea and its variations. The classical technique to insert electrode arrays through a drilled cochleostomy has been abandoned by some surgeons today. Instead a round-window approach can be used as originally implemented by William House for short electrodes. This so-called 'hook' region of the cochlea presents extensive anatomical variations that can be difficult to foresee on pre-operative computed tomography. CI depends on the functional status of remaining spiral ganglion neurons. These cells are more or less preserved in CI patients but how the conservation influences the outcome of CI is debatable. Notwithstanding their preservation is crucial and more information should be attained about their deterioration and how it can be prevented. Better understanding of structure, function, and regenerative capability is needed to comprehend the nature of electrical stimulation of the peripheral and central nervous system to improve the design of future implant systems.
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| 6. |
- Rask-Andersen, Helge, et al.
(författare)
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Supernumerary human hair cells-signs of regeneration or impaired development? : A field emission scanning electron microscopy study
- 2017
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Ingår i: Upsala Journal of Medical Sciences. - : TAYLOR & FRANCIS LTD. - 0300-9734 .- 2000-1967. ; 122:1, s. 11-19
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Tidskriftsartikel (refereegranskat)abstract
- Background: Current attempts to regenerate cochlear sensorineural structures motivate further inspection of the human organ of hearing. Here, we analyzed the supernumerary inner hair cell (sIHC), a possible sign of regeneration and cell replacement. Methods: Human cochleae were studied using field emission scanning electron microscopy (FESEM; maximum resolution 2 nm) obtained from individuals aged 44, 48, and 58 years with normal sensorineural pure-tone average (PTA) thresholds (PTA < 20 dB). The wasted tissue was harvested during trans-cochlear approaches and immediately fixed for ultrastructural analysis. Results: All specimens exhibited sIHCs at all turns except at the extreme lower basal turn. In one specimen, it was possible to image and count the inner hair cells (IHCs) along the cochlea representing the 0.2 kHz-8 kHz region according to the Greenwood place/frequency scale. In a region with 2,321 IHCs, there were 120 scattered one-cell losses or 'gaps' (5%). Forty-two sIHCs were present facing the modiolus. Thirty-eight percent of the sIHCs were located near a 'gap' in the IHC row (+/- 6 IHCs). Conclusions: The prevalence of ectopic inner hair cells was higher than expected. The morphology and placement could reflect a certain ongoing regeneration. Further molecular studies are needed to verify if the regenerative capacity of the human auditory periphery might have been underestimated.
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