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  • 1.
    Anderson, Malin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Boström, Marja
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Pfaller, Kristian
    Glueckert, Rudolf
    Schrott-Fischer, Annelies
    Gerdin, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Plastic Surgery.
    Rask-Andersen, Helge
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Structure and locomotion of adult in vitro regenerated spiral ganglion growth cones: a study using video microscopy and SEM2006In: Hearing Research, ISSN 0378-5955, E-ISSN 1878-5891, Vol. 215, no 1-2, p. 97-107Article in journal (Refereed)
    Abstract [en]

    Neuronal development and neurite regeneration depends on the locomotion and navigation of nerve growth cones (GCs). There are few detailed descriptions of the GC function and structure in the adult auditory system. In this study, GCs of adult dissociated and cultured spiral ganglion (SG) neurons were analyzed in vitro utilizing combined high resolution scanning electron microscopy (SEM) and time lapse video microscopy (TLVM). Axon kinesis was assessed on planar substratum with growth factors BDNF, NT-3 and GDNF. At the nano-scale level, lamellipodial abdomen of the expanding GC was found to be decorated with short surface specializations, which at TLVM were considered to be related to their crawling capacity. Filopodia were devoid of these surface structures, supporting its generally described sensory role. Microspikes appearing on lamellipodia and axons, showed circular adhesions, which at TLVM were found to provide anchorage of the navigating and turning axon. Neurons and GCs expressed the DCC-receptor for the guidance molecule netrin-1. Asymmetric ligand-based stimulation initiated turning responses suggest that this attractant cue influences steering of GC in adult regenerating auditory neurites. Hopefully, these findings may be used for ensuing tentative navigation of spiral ganglion neurons to induce regenerative processes in the human ear.

  • 2.
    Berggren, Diana
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Liu, Wei
    Department of Otolaryngology, Albert Einstein College of Medicine, New York, NY.
    Frenz, Dorothy
    Department of Otolaryngology, Albert Einstein College of Medicine, New York, NY.
    Van De Water, Thomas
    Cochlear Implant Research Program, Department of Otolaryngology, University of Miami Ear Institute, University of Miami, School of Medicine, 1600 N.W. 10th Avenue, RMSB 3160, Miami.
    Spontaneous hair-cell renewal following gentamicin exposure in postnatal rat utricular explants2003In: Hearing Research, ISSN 0378-5955, E-ISSN 1878-5891, Vol. 180, no 1-2, p. 114-125Article in journal (Refereed)
    Abstract [en]

    We have established an in vitro model of long-time culture of 4-day-old rat utricular maculae to study aminoglycoside-induced vestibular hair-cell renewal in the mammalian inner ear. The explanted maculae were cultured for up to 28 days on the surface of a membrane insert system. In an initial series of experiments utricles were exposed to 1 mM of gentamicin for 48 h and then allowed to recover in unsupplemented medium or in medium supplemented with the anti-mitotic drug aphidicolin. In a parallel control series, explants were not exposed to gentamicin. Utricles were harvested at specified time points from the second through the 28th day in vitro. Whole-mount utricles were stained with phalloidin-fluorescein isothiocyanate and their stereociliary bundles visualized and counted. In a second experimental series 2'-bromo-5'deoxyuridine labeling was used to confirm the antimitotic efficacy of aphidicolin. Loss of hair-cell stereociliary bundles was nearly complete 3 days after exposure to gentamicin, with the density of stereociliary bundles only 3-4% of their original density. Renewal of hair-cell bundles was abundant (i.e. 15x increase) in cultures in unsupplemented medium, with a peak of stereociliary bundle renewal reached after 21 days in vitro. A limited amount of hair-cell renewal also occurred in the presence of the anti-mitotic drug, aphidicolin. These results suggest that spontaneous renewal of hair-cell stereociliary bundles following gentamicin damage in utricular explants predominantly follows a pathway that includes mitotic events, but that a small portion of the hair-cell stereociliary bundle renewal does not require mitotic activity.

  • 3. Björn, Palmgren
    et al.
    Jin, Zhe
    Ma, Hongmin
    Jiao, Yu
    Olivius, Petri
    β-Bungarotoxin application to the round window: An in vivo deafferentation model of the inner ear2010In: Hearing Research, ISSN 0378-5955, E-ISSN 1878-5891, Vol. 265, p. 70-76Article in journal (Refereed)
    Abstract [en]

    Hearing impairment can be caused by a primary lesion to the spiral ganglion neurons (SGNs) with the hair cells kept intact, for example via tumours, trauma or auditory neuropathy. To mimic these conditions in animal models various methods of inflicting damage to the inner ear have been used. However, only a few methods have a selective effect on the SGNs, which is of importance since it might be clinically more relevant to study hearing impairment with the hair cells undamaged. β-Bungarotoxin is a venom of the Taiwan banded krait, which in vitro has been shown to induce apoptosis in neurons, leaving remaining cochlear cells intact. We wanted to create an in vivo rat model of selective damage to primary auditory neurons. Under deep anaesthesia, 41 rats received β-Bungarotoxin or saline to the round window niche. At postoperative intervals between days 3 and 21 auditory brainstem response (ABR) measurement, immunohistochemistry, SGN quantification and cochlear surface preparation were performed. The results in the β-Bungarotoxin-treated ears, as compared with sham-operated ears, show significantly increased ABR thresholds at all postoperative intervals, illustrating a severe to profound hearing loss at all tested frequencies (3.5, 7, 16 and 28 kHz). Quantification of the SGNs showed no obvious reduction in neuronal numbers until 14 days postoperatively. Between days 14 and 21 a significant reduction in SGN numbers was observed. Cochlear surface preparation and immunohistochemistry showed that the hair cells were intact. Our results illustrate that in vivo application of β-Bungarotoxin to the round window niche is a feasible way of deafening rats by SGN reduction while the hair cells are kept intact.

  • 4. Canlon, Barbara
    et al.
    Theorell, Töres
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institute, Sweden.
    Hasson, Dan
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    Associations between stress and hearing problems in humans2013In: Hearing Research, ISSN 0378-5955, E-ISSN 1878-5891, Vol. 295, no 1-2, p. 9-15Article in journal (Refereed)
    Abstract [en]

    Hearing problems are a public health issue with prevalence figures far more common than previously estimated. There are well-established risk factors of hearing problems such as age, sex and noise exposure history. Here, we demonstrate additional risk factors, i.e. socioeconomic status and long-term stress exposure that are found to increase the risk of hearing problems. In order to proactively intervene and prevent hearing problems, these newly recognized risk factors need to be taken into consideration. When taking these new risk factors into account, sex differences become even more apparent than previously found. The aim of this review is to summarize our recent findings about the associations between stress and hearing problems.

  • 5. Carlsson, Per-Inge
    et al.
    Van Laer, Lut
    Borg, Erik
    Bondeson, Marie-Louise
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Thys, Melissa
    Fransen, Erik
    Van Camp, Guy
    The influence of genetic variation in oxidative stress genes on human noise susceptibility2005In: Hearing Research, ISSN 0378-5955, E-ISSN 1878-5891, Vol. 202, no 1-2, p. 87-96Article in journal (Refereed)
    Abstract [en]

    Noise induced hearing loss (NIHL) is a complex disease caused by an interaction between genetic and environmental factors. Damage in the cochlea as a result of noise exposure appears to be mediated by reactive oxygen species (ROS). To investigate whether genetic variation in the human protective antioxidant system is associated with high or low susceptibility to NIHL, genetic polymorphisms derived from genes involved in the oxidative stress response were analysed in the 10% most susceptible and 10% most resistant extremes of 1200 Swedish noise-exposed workers. The genetic polymorphisms included 2 deletion polymorphisms for the GSTM1 and GSTT1 gene, and 14 SNPs derived from the CAT, SOD, GPX, GSR and GSTP1 genes. No significant differences were found between susceptible and resistant groups, providing no support for a major role of genetic variation of antioxidant enzymes in the susceptibility to NIHL.

  • 6.
    Carlsson, Per-Inge
    et al.
    Örebro University, Department of Nursing and Caring Sciences.
    Van Lear, Lut
    Borg, Erik
    Bondeson, Marie-Louise
    Thys, Melissa
    Fransen, Erik
    Van Camp, Guy
    The influence of genetic variation in oxidative stress genes on human noise susceptibility2005In: Hearing Research, ISSN 0378-5955, E-ISSN 1878-5891, Vol. 202, no 1-2, p. 87-96Article in journal (Refereed)
  • 7. Couchman, Kiri
    et al.
    Garrett, Andrew
    Deardorff, Adam S
    Rattay, Frank
    Resatz, Susanne
    Fyffe, Robert
    Walmsley, Bruce
    Leão, Richardson N
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Lateral superior olive function in congenital deafness2011In: Hearing Research, ISSN 0378-5955, E-ISSN 1878-5891, Vol. 277, no 1-2, p. 163-175Article in journal (Refereed)
    Abstract [en]

    The development of cochlear implants for the treatment of patients with profound hearing loss has advanced considerably in the last few decades, particularly in the field of speech comprehension. However, attempts to provide not only sound decoding but also spatial hearing are limited by our understanding of circuit adaptations in the absence of auditory input. Here we investigate the lateral superior olive (LSO), a nucleus involved in interaural level difference (ILD) processing in the auditory brainstem using a mouse model of congenital deafness (the dn/dn mouse). An electrophysiological investigation of principal neurons of the LSO from the dn/dn mouse reveals a higher than normal proportion of single spiking (SS) neurons, and an increase in the hyperpolarisation-activated I(h) current. However, inhibitory glycinergic input to the LSO appears to develop normally both pre and postsynaptically in dn/dn mice despite the absence of auditory nerve activity. In combination with previous electrophysiological findings from the dn/dn mouse, we also compile a simple Hodgkin and Huxley circuit model in order to investigate possible computational deficits in ILD processing resulting from congenital hearing loss. We find that the predominance of SS neurons in the dn/dn LSO may compensate for upstream modifications and help to maintain a functioning ILD circuit in the dn/dn mouse. This could have clinical repercussions on the development of stimulation paradigms for spatial hearing with cochlear implants.

  • 8.
    Cros, Olivier
    et al.
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, The Institute of Technology.
    Borga, Magnus
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, The Institute of Technology.
    Pauwels, Elin
    University of Ghent, Belgium.
    Dirckx, Joris J. J.
    University of Antwerp, Belgium.
    Gaihede, Michael
    Aalborg University Hospital, Denmark.
    Micro-channels in the mastoid anatomy. Indications of a separate blood supply of the air cell system mucosa by micro-CT scanning2013In: Hearing Research, ISSN 0378-5955, E-ISSN 1878-5891, Vol. 301, p. 60-65Article in journal (Refereed)
    Abstract [en]

    The mastoid air cell system has traditionally been considered to have a passive role in gas exchange and pressure regulation of the middle ear possibly with some acoustic function. However, more evidence has focused on the mucosa of the mastoid, which may play a more active role in regulation of middle ear pressure.

    In this study we have applied micro-CT scanning on a series of three human temporal bones. This approach greatly enhances the resolution (40–60 μm), so that we have discovered anatomical details, which has not been reported earlier. Thus, qualitative analysis using volume rendering has demonstrated notable micro-channels connecting the surface of the compact bone directly to the mastoid air cells as well as forming a network of connections between the air cells. Quantitative analysis on 2D slices was employed to determine the average diameter of these micro-channels (158 μm; range = 40–440 μm) as well as their density at a localized area (average = 75 cm−2; range = 64–97 cm−2).

    These channels are hypothesized to contain a separate vascular supply for the mastoid mucosa. However, future studies of the histological structure of the micro-channels are warranted to confirm the hypothesis. Studies on the mastoid mucosa and its blood supply may improve our knowledge of its physiological properties, which may have important implications for our understanding of the pressure regulation of the middle ear.

  • 9.
    Cros, Olivier
    et al.
    Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, The Institute of Technology. Linköping University, Center for Medical Image Science and Visualization (CMIV). Department of Otolaryngology, Head and Neck Surgery, Aalborg Hospital, Aarhus University Hospital, Denmark.
    Gaihede, Michael L.
    Department of Otolaryngology, Head and Neck Surgery, Aalborg Hospital, Aarhus University Hospital, Denmark.
    Borga, Magnus
    Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, The Institute of Technology. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Smedby, Örjan
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Radiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Radiology in Linköping.
    Mastoid structural properties determined by imaging analysis of high resolution CT-scanning2010In: Hearing Research, ISSN 0378-5955, E-ISSN 1878-5891, Vol. 263, no 1-2, p. 242-243Article in journal (Refereed)
    Abstract [en]

    Hypothesis: The structure of the mastoid air cells can be described by quantitative imaging analysis of high-resolution CT-scans, which may contribute to understand its function in normal and pathological ears. Background: Negative middle ear pressure is a common factor in middle ear diseases resulting from an imbalance between mastoid gas exchange and Eustachian tube function. While the Eustachian tube function has been the main focus of research, more recent studies indicate that the mastoid may play an active role in pressure regulation. The mastoid structure with numerous air cells reflects a large area to volume ratio (AV-ratio) adapted to efficient gas exchange. Imaging analysis applied to high resolution CT-scanning can describe quantitative measures, which may reveal important information about mastoid function and its role in healthy and diseased ears. Materials and methods: Quantitative analysis was performed on a series of unselected high resolution CT-scans (voxel size: 0.29 _ 0.29 _ 0.625 mm) from 36 ears in 24 patients. Area and volume were determined using Cavalieri’s method, i.e. by summing cross-sectional areas. The AV-ratio was computed for each scan. Results: Mean area was 69 cm2 (range: 23–134cm2), mean volume was 4 cm3 (range: 1.3–10.8 cm3), and mean AV-ratio was 16 cm-1 (range: 11.2–21.0 cm-1). The area correlated linearly to the volume by A = 17.2*V-0.2. Conclusion: The area and volume values corresponded with previous studies, and the additional AV-ratio reflected the functional properties of the mastoid in terms of capability for gas exchange. Due to a series of similarities between structure and function of the lungs and mastoid, it seems likely to propose a tree-structure of dividing mastoid cells. In respiratory research, analysis describing the dimensions of series of bronchi generations has been applied, and based on current results; our aim of future research is to establish similar details of mastoid tree-structure. Funding source: Various private Danish funds.

  • 10.
    Cros, Olivier
    et al.
    Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, Faculty of Science & Engineering. Linköping University, Center for Medical Image Science and Visualization (CMIV). Department of Otolaryngology, Head and Neck Surgery, Aalborg University Hospital, Denmark.
    Knutsson, Hans
    Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, Faculty of Science & Engineering. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Andersson, Mats
    Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, Faculty of Science & Engineering. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Pawels, Elin
    Centre for X-ray Tomography, Department of Physics and Astronomy, University of Ghent, Belgium.
    Borga, Magnus
    Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, Faculty of Science & Engineering. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Gaihede, Michael
    Department of Otolaryngology, Head and Neck Surgery, Aalborg University Hospital, Denmark / Department of Clinical Medicine, Aalborg University, Denmark.
    Determination of the mastoid surface area and volume based on micro-CT scanning of human temporal bone: Geometrical parameters dependence on scanning resolutions2016In: Hearing Research, ISSN 0378-5955, E-ISSN 1878-5891, Vol. 340, p. 127-134Article in journal (Refereed)
    Abstract [en]

    The mastoid air cell system (MACS) with its large complex of interconnected air cells reflects an enhanced surface area (SA) relative to its volume (V), which may indicate that the MACS is adapted to gas exchange and has a potential role in middle ear pressure regulation. Thus, these geometric parameters of the MACS have been studied by high resolution clinical CT scanning. However, the resolution of these scans is limited to a voxel size of around 0.6 mm in all dimensions, and so, the geometrical parameters are also limited. Small air cells may appear below the resolution and cannot be detected. Such air cells may contribute to a much higher SA than the V, and thus, also the SA/V ratio. More accurate parameters are important for analysis of the function of the MACS including physiological modeling.

    Our aim was to determine the SA, V, and SA/V ratio in MACS in human temporal bones at highest resolution by using micro-CT-scanning. Further, the influence of the resolution on these parameters was investigated by downsampling the data. Eight normally aerated temporal bones were scanned at the highest possible resolution (30-60 μm). The SA was determined using a triangular mesh fitted onto the segmented MACS. The V was determined by summing all the voxels containing air. Downsampling of the original data was applied four times by a factor of 2.

    The mean SA was 194 cm2, the mean V was 9 cm3, and the mean SA/V amounted to 22 cm-1. Decreasing the resolution resulted in a non-linear decrement of SA and SA/V, whereas V was mainly independent of the resolution.

    The current study found significantly higher SA and SA/V compared with previous studies using clinical CT scanning at lower resolutions. These findings indicate a separate role of the MACS compared with the tympanum, and the results are important for a more accurate modeling of the middle ear physiology.

  • 11.
    Dobrev, Ivo
    et al.
    University Hospital Zurich, Switzerland; University of Zurich, Switzerland.
    Hoon Sim, Jae
    University Hospital Zurich, Switzerland; University of Zurich, Switzerland.
    Stenfelt, Stefan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Speech language pathology, Audiology and Otorhinolaryngology. Linköping University, Faculty of Medicine and Health Sciences.
    Ihrle, Sebastian
    University of Stuttgart, Germany.
    Gerig, Rahel
    University Hospital Zurich, Switzerland; University of Zurich, Switzerland.
    Pfiffner, Flurin
    University Hospital Zurich, Switzerland; University of Zurich, Switzerland.
    Eiber, Albrecht
    University of Stuttgart, Germany.
    Huber, Alexander M.
    University Hospital Zurich, Switzerland; University of Zurich, Switzerland.
    Roosli, Christof
    University Hospital Zurich, Switzerland; University of Zurich, Switzerland.
    Sound wave propagation on the human skull surface with bone conduction stimulation2017In: Hearing Research, ISSN 0378-5955, E-ISSN 1878-5891, Vol. 355Article in journal (Refereed)
    Abstract [en]

    Background: Bone conduction (BC) is an alternative to air conduction to stimulate the inner ear. In general, the stimulation for BC occurs on a specific location directly on the skull bone or through the skin covering the skull bone. The stimulation propagates to the ipsilateral and contralateral cochlea, mainly via the skull bone and possibly via other skull contents. This study aims to investigate the wave propagation on the surface of the skull bone during BC stimulation at the forehead and at ipsilateral mastoid. Methods: Measurements were performed in five human cadaveric whole heads. The electro-magnetic transducer from a BCHA (bone conducting hearing aid), a Baha (R) Cordelle II transducer in particular, was attached to a percutaneously implanted screw or positioned with a 5-Newton steel headband at the mastoid and forehead. The Baha transducer was driven directly with single tone signals in the frequency range of 0.25-8 kHz, while skull bone vibrations were measured at multiple points on the skull using a scanning laser Doppler vibrometer (SLDV) system and a 3D LDV system. The 3D velocity components, defined by the 3D LDV measurement coordinate system, have been transformed into tangent (in-plane) and normal (out-of-plane) components in a local intrinsic coordinate system at each measurement point, which is based on the cadaver heads shape, estimated by the spatial locations of all measurement points. Results: Rigid-body-like motion was dominant at low frequencies below 1 kHz, and clear transverse traveling waves were observed at high frequencies above 2 kHz for both measurement systems. The surface waves propagation speeds were approximately 450 m/s at 8 kHz, corresponding trans-cranial time interval of 0.4 ms. The 3D velocity measurements confirmed the complex space and frequency dependent response of the cadaver heads indicated by the ID data from the SLDV system. Comparison between the tangent and normal motion components, extracted by transforming the 3D velocity components into a local coordinate system, indicates that the normal component, with spatially varying phase, is dominant above 2 kHz, consistent with local bending vibration modes and traveling surface waves. Conclusion: Both SLDV and 3D LDV data indicate that sound transmission in the skull bone causes rigid body-like motion at low frequencies whereas transverse deformations and travelling waves were observed above 2 kHz, with propagation speeds of approximately of 450 m/s at 8 kHz. (C) 2017 Elsevier B.V. All rights reserved.

  • 12.
    Eeg-Olofsson, Måns
    et al.
    Sahlgrenska University Hospital, Göteborg University, Sweden.
    Stenfelt, Stefan
    Linköping University, Department of Clinical and Experimental Medicine, Technical Audiology. Linköping University, Faculty of Health Sciences.
    Taghavi, Hamidreza
    Chalmers University of Technology, Göteborg, Sweden.
    Reinfeldt, Sabine
    Chalmers University of Technology, Göteborg, Sweden.
    Håkansson, Bo
    Chalmers University of Technology, Göteborg, Sweden.
    Tengstrand, Tomas
    Sahlgrenska University Hospital, Göteborg, Sweden.
    Finizia, Chatarina
    Sahlgrenska University Hospital, Göteborg University, Sweden.
    Transmission of bone conducted sound – Correlation between hearing perception and cochlear vibration2013In: Hearing Research, ISSN 0378-5955, E-ISSN 1878-5891, Vol. 306, p. 11-20Article in journal (Refereed)
    Abstract [en]

    The vibration velocity of the lateral semicircular canal and the cochlear promontory was measured on 16 subjects with a unilateral middle ear common cavity, using a laser Doppler vibrometer, when the stimulation was by bone conduction (BC). Four stimulation positions were used: three ipsilateral positions and one contralateral position. Masked BC pure tone thresholds were measured with the stimulation at the same four positions. Valid vibration data were obtained at frequencies between 0.3 and 5.0 kHz. Large intersubject variation of the results was found with both methods. The difference in cochlear velocity with BC stimulation at the four positions varied as a function of frequency while the tone thresholds showed a tendency of lower thresholds with stimulation at positions close to the cochlea. The correlation between the vibration velocities of the two measuring sites of the otic capsule was high. Also, relative median data showed similar trends for both vibration and threshold measurements. However, due to the high variability for both vibration and perceptual data, low correlation between the two methods was found at the individual level. The results from this study indicated that human hearing perception from BC sound can be estimated from the measure of cochlear vibrations of the otic capsule. It also showed that vibration measurements of the cochlea in cadaver heads are similar to that measured in live humans.

  • 13. Felder, E
    et al.
    Kanonier, G
    Scholtz, A
    Rask-Andersen, Helge
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Schrott-Fischer, A
    Quantitative evaluation of cochlear neurons and computer-aided three-dimensional reconstruction of spiral ganglion cells in humans with a peripheral loss of nerve fibres1997In: Hearing Research, ISSN 0378-5955, E-ISSN 1878-5891, Vol. 105, no 1-2, p. 183-190Article in journal (Refereed)
    Abstract [en]

    Quantitative data on human cochlear neuronal elements were collected from various regions in five patients with high-tone hearing loss due to presbycusis and in two patients with normal hearing. The number of nerve fibers was assessed in the spiral lamina and in the inner acoustic meatus together with counts of spiral ganglion cells. The results show that the number of neurons decreased peripherally, i.e., with increasing distance from the central nervous system in patients with high-tone hearing loss due to presbycusis. In two patients with normal hearing no significant difference in the number of neurons was found in the lamina spiralis as compared to the inner acoustic canal. Computer-aided 3-dimensional reconstruction of the human spiral ganglion displayed large bipolar neurons (type I cells), but also large ganglion cells with one missing axon. The results may indicate that a slow retrograde degeneration occurs from the periphery towards the spiral ganglion in presbycusis. Transmission electron microscopy analysis of freshly fixed human spiral ganglions displayed interneural connections. It is speculated whether a trophic supply from other neurons at the level of the spiral ganglion can prevent or delay further degeneration of the central axon.

  • 14.
    Flock, Å.
    et al.
    Karolinska Institute, Stockholm, Sweden.
    Flock, B.
    Karolinska Institute, Stockholm, Sweden.
    Fridberger, Anders
    Karolinska Institute, Stockholm, Sweden.
    Jäger, W.
    Huddinge Hospital, Sweden.
    Methods for integrating fluorimetry in the study of hearing organ structure and function1997In: Hearing Research, ISSN 0378-5955, E-ISSN 1878-5891, Vol. 106, no 1-2, p. 29-38Article in journal (Refereed)
    Abstract [en]

    The measurement of function in the intact organ of Corti has up to now been achieved by three methods: electrophysiology, mechanical measurement and biochemical analysis. The two former methods have supplied information at the level of single identified cells. We have used a fourth method, optical fluorimetry, to measure hair cell function at the cellular level in the intact organ of Corti. Here we describe the methods involved in fluorescence labelling and video-enhanced microscopy in combination with electrophysiological recording of cochlear microphonic (CM) and summating potentials (SP). The guinea pig temporal bone containing an intact ear drum, ossicular chain and cochlea can be maintained in the isolated state by perfusion of the scala tympani with oxygenated tissue culture medium. Substances added to the perfusate readily diffuse through the basilar membrane into the organ of Corti. In this way cells in the organ can be stained by a number of fluorescent probes which label different structures and functions. Here we have used two dyes which label mitochondria and fluoresce with an intensity proportional to metabolic activity. By simultaneous measurement of CM and SP the functional state of the organ can be monitored.

  • 15.
    Fridberger, Anders
    et al.
    Karolinska Institutet, Stockholm, Sweden.
    Zheng, Jiefu
    Oregon Health Sciences University, Portland, USA.
    Nuttall, Alfred
    University of Michigan, Ann Arbor, USA.
    Alterations of basilar membrane response phase and velocity after acoustic overstimulation2002In: Hearing Research, ISSN 0378-5955, E-ISSN 1878-5891, Vol. 167, no 1-2, p. 214-222Article in journal (Refereed)
    Abstract [en]

    To investigate the physiology of noise-induced hearing loss, the sound-induced vibrations of the basilar membrane (BM) of the inner ear were measured in living anesthetized guinea pigs before and after intense sound exposure. The vibrations were measured using a laser Doppler velocimeter after placing reflective glass beads on the BM. Pseudo-random noise waveforms containing frequencies between 4 and 24 kHz were used to generate velocity tuning curves. Before overstimulation, sharp response peaks were seen at stimulus frequencies between 15 and 17 kHz, consistent with the expected best frequency of the recording location. The response to low level stimuli lagged the high level ones by up to 90 degrees at the characteristic frequency. Following exposure to loud sound, the BM vibrations showed a pronounced reduction in amplitude, primarily at low stimulus levels, and the best frequency moved to approximately 12 kHz. At higher levels, the reduction was either absent or much smaller. In addition to the amplitude changes, increased phase lags were seen at frequencies near the characteristic frequency. In animals with more severe exposures, response phases were altered also at frequencies showing no change of the amplitude. The phase was independent of stimulus level after severe exposures.

  • 16.
    Glueckert, R.
    et al.
    Med Univ Innsbruck, Dept Otolaryngol, Innsbruck, Austria;Univ Clin Ear Nose & Throat Med Innsbruck, Univ Clin Innsbruck, Tirol Kliniken, Innsbruck, Austria.
    Chacko, L. Johnson
    Med Univ Innsbruck, Dept Otolaryngol, Innsbruck, Austria.
    Rask-Andersen, Helge
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Liu, Wei
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Handschuh, S.
    Univ Vet Med, VetImaging, VetCore Facil Res, Vienna, Austria.
    Schrott-Fischer, A.
    Med Univ Innsbruck, Dept Otolaryngol, Innsbruck, Austria.
    Anatomical basis of drug delivery to the inner ear2018In: Hearing Research, ISSN 0378-5955, E-ISSN 1878-5891, Vol. 368, p. 10-27Article, review/survey (Refereed)
    Abstract [en]

    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.

  • 17. Grondin, Yohann
    et al.
    Cotanche, Douglas A
    Manneberg, Otto
    KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Molina, Ramon
    Treviño-Villarreal, J Humberto
    Sepulveda, Rosalinda
    Clifford, Royce
    Bortoni, Magda E
    Forsberg, Scott
    Labrecque, Brian
    Altshul, Larisa
    Brain, Joseph D
    Jackson, Ronald L
    Rogers, Rick A
    Pulmonary delivery of d-methionine is associated with an increase in ALCAR and glutathione in cochlear fluids.2013In: Hearing Research, ISSN 0378-5955, E-ISSN 1878-5891, Vol. 298, p. 93-103Article in journal (Refereed)
    Abstract [en]

    In animals, hearing loss resulting from cochlear mechanosensory cell damage can be mitigated by antioxidants such as d-methionine (d-met) and acetyl-l-carnitine (ALCAR). The systemic routes of administration of these compounds, that must of necessity transit trough the cochlear fluids, may affect the antioxidant levels in the cochlea and the resulting oto-protective effect. In this study, we analyzed the pharmacokinetics of [C]d-met in the cochlea and four other tissues after intratracheal (IT), intranasal (IN), and oral by gavage (OG) administration and compared it to intravenous administration (IV). We then analyzed the effect of these four routes on the antioxidant content of the cochlear fluids after d-met or ALCAR administration, by liquid chromatography/mass spectrometry. Our results showed that the concentration of methionine and ALCAR in cochlear fluids significantly increased after their respective systemic administration. Interestingly, d-met administration also contributed to an increase of ALCAR. Our results also showed that the delivery routes differently affected the bioavailability of administered [C]d-met as well as the concentrations of methionine, ALCAR and the ratio of oxidized to reduced glutathione. Overall, pulmonary delivery via IT administration achieved high concentrations of methionine, ALCAR, and oxidative-related metabolites in cochlear fluids, in some cases surpassing IV administration, while IN route appeared to be the least efficacious. To our knowledge, this is the first report of the direct measurements of antioxidant levels in cochlear fluids after their systemic administration. This report also demonstrates the validity of the pulmonary administration of antioxidants and highlights the different contributions of d-met and ALCAR allowing to further investigate their impact on oxidative stress in the cochlear microenvironment.

  • 18.
    Hartel, Bas P.
    et al.
    Department of Otorhinolaryngology, Radboud University Medical Center, Nijmegen, the Netherlands; Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, the Netherlands.
    Löfgren, Maria
    Swedish Institute for Disability Research (SIDR), Linköping Uiniversity, Linköping, Sweden; Audiological Research Centre, Örebro University Hospital, Örebro, Sweden; School of Medicine and Health, Örebro University, Örebro, Sweden.
    Huygen, Patrick L. M.
    Department of Otorhinolaryngology, Radboud University Medical Center, Nijmegen, the Netherlands; Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, the Netherlands.
    Guchelaar, Iris
    Department of Otorhinolaryngology, Radboud University Medical Center, Nijmegen, the Netherlands; Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, the Netherlands.
    Lo-A-Njoe Kort, Nicole
    Department of Otorhinolaryngology, Radboud University Medical Center, Nijmegen, the Netherlands; Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, the Netherlands.
    Sadeghi, Andre M.
    The Sahlgrenska Academy, Institute of Neuroscience and Physiology, Department of Audiology, Göteborg, Sweden; Hearing and deafness activities organization, Habilitation & Health, Göteborg, Sweden.
    van Wijk, Erwin
    Department of Otorhinolaryngology, Head, and Neck Surgery, Radboud University Medical Center, Nijmegen, The Netherlands; Radboud Institute for Molecular Life Sciences, Nijmegen, The Netherlands.
    Tranebjærg, Lisbeth
    Department of Cellular and Molecular Medicine, University of Copenhagen, Copenhagen, Denmark; Department of Otorhinolaryngology, Head and Neck Surgery and Audiology, Bispebjerg Hospital/Rigshospitalet, Copenhagen, Denmark.
    Kremer, Hannie
    Department of Otorhinolaryngology, Head, and Neck Surgery, Radboud University Medical Center, Nijmegen, The Netherlands; Radboud Institute for Molecular Life Sciences, Nijmegen, The Netherlands; Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.
    Kimberling, William J.
    Department of Otolaryngology, Molecular Otolaryngology, and Renal Research Laboratories, University of Iowa, Iowa City IA, United States of America.
    Cremers, Cor W. R. J.
    Department of Otorhinolaryngology, Radboud University Medical Center, Nijmegen, the Netherlands; Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, the Netherlands.
    Möller, Claes
    Örebro University, School of Health Sciences. Swedish Institute for Disability Research (SIDR), Linköping, Sweden; Audiological Research Centre, Örebro University Hospital, Örebro, Sweden; Department of Otolaryngology, Molecular Otolaryngology, and Renal Research Laboratories, University of Iowa, Iowa City IA, USA .
    Pennings, Ronald J. E.
    Department of Otorhinolaryngology, Donders Institute for Brain, Cognition and Behaviour, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands; Department of Otolaryngology, Molecular Otolaryngology, and Renal Research Laboratories, University of Iowa, Iowa City IA, USA.
    A combination of two truncating mutations in USH2A causes more severe and progressive hearing impairment in Usher syndrome type IIa2016In: Hearing Research, ISSN 0378-5955, E-ISSN 1878-5891, Vol. 339, p. 60-68Article in journal (Refereed)
    Abstract [en]

    Objectives: Usher syndrome is an inherited disorder that is characterized by hearing impairment (HI), retinitis pigmentosa, and in some cases vestibular dysfunction. Usher syndrome type IIa is caused by mutations in USH2A. HI in these patients is highly heterogeneous and the present study evaluates the effects of different types of USH2A mutations on the audiometric phenotype. Data from two large centres of expertise on Usher Syndrome in the Netherlands and Sweden were combined in order to create a large combined sample of patients to identify possible genotype-phenotype correlations.

    Design: A retrospective study on HI in 110 patients (65 Dutch and 45 Swedish) genetically diagnosed with Usher syndrome type IIa. We used methods especially designed for characterizing and testing differences in audiological phenotype between patient subgroups. These methods included Age Related Typical Audiograms (ARTA) and a method to evaluate the difference in the degree of HI developed throughout life between subgroups.

    Results: Cross-sectional linear regression analysis of last-visit audiograms for the best hearing ear demonstrated a gradual decline of hearing over decades. The congenital level of HI was in the range of 16-33 dB at 0.25-0.5 kHz, and in the range of 51-60 dB at 1-8 kHz. The annual threshold deterioration was in the range of 0.4-0.5 dB/year at 0.25-2 kHz and in the range of 0.7-0.8 dB/year at 4-8 kHz. Patients with two truncating mutations, including homozygotes for the common c.2299delG mutation, developed significantly more severe HI throughout life than patients with one truncating mutation combined with one nontruncating mutation, and patients with two nontruncating mutations.

    Conclusions: The results have direct implications for patient counselling in terms of prognosis of hearing and may serve as baseline measures for future (genetic) therapeutic interventions.

  • 19. Henson, M.M.
    et al.
    Madden, V.J.
    Rask-Andersen, Helge
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Henson, O.W. jr
    Smooth muscle in the annulus fibrosus of the tympanic membrane in bats, rodents, insectivores and humans2005In: Hearing Research, ISSN 0378-5955, E-ISSN 1878-5891, Vol. 200, no 1-2, p. 29-37Article in journal (Refereed)
    Abstract [en]

    The annulus fibrosus and its attachment to the bony tympanic ring were studied in a series of mammals. In the pallid bat, Antrozous pallidus, there is an extensive plexus of large interconnected blood sinuses in the part of the annulus that borders the tympanic bone. The spaces between the sinuses are packed with smooth muscle cells. Most of the cells have a predominately radial orientation; they extend from the bony tympanic sulcus to a dense collagenous matrix (apical zone) where radially oriented fibers of the pars tensa are confluent with the annulus. The muscles and vessels constitute a myovascular zone. A structurally similar myovascular zone is also present in the European hedgehog. In rodents, the annulus lacks the large interconnected blood sinuses but many small vessels are present. Smooth muscle is concentrated in the broad area of attachment of the annulus to the tympanic bone. In the gerbil, smooth muscle seems to be concentrated in the central part of the width of the annulus where it is attached to bone and radiates toward the tympanic membrane. In humans collections of radially oriented smooth muscle cells were found in several locations. The smooth muscle in all species studied appears to form a rim of contractile elements for the pars tensa. This arrangement suggests a role in controlling blood flow and/or creating and maintaining tension on the tympanic membrane.

  • 20. Jin, Zhe
    et al.
    Mannström, Paula
    Skjönsberg, Åsa
    Järlebark, Leif
    Ulfendahl, Mats
    Auditory function and cochlear morphology in the German waltzing guinea pig2006In: Hearing Research, ISSN 0378-5955, E-ISSN 1878-5891, Vol. 219Article in journal (Refereed)
  • 21.
    Koelewijn, Thomas
    et al.
    Vrije University of Amsterdam Medical Centre, Netherlands; Vrije University of Amsterdam Medical Centre, Netherlands.
    de Kluiver, Hilde
    Vrije University of Amsterdam Medical Centre, Netherlands; Vrije University of Amsterdam Medical Centre, Netherlands.
    Shinn-Cunningham, Barbara G.
    Boston University, MA 02215 USA.
    Zekveld, Adriana
    Linköping University, Department of Behavioural Sciences and Learning. Linköping University, The Swedish Institute for Disability Research. Vrije University of Amsterdam Medical Centre, Netherlands; Vrije University of Amsterdam Medical Centre, Netherlands.
    Kramer, Sophia E.
    Vrije University of Amsterdam Medical Centre, Netherlands; Vrije University of Amsterdam Medical Centre, Netherlands.
    The pupil response reveals increased listening effort when it is difficult to focus attention2015In: Hearing Research, ISSN 0378-5955, E-ISSN 1878-5891, Vol. 323, p. 81-90Article in journal (Refereed)
    Abstract [en]

    Recent studies have shown that prior knowledge about where, when, and who is going to talk improves speech intelligibility. How related attentional processes affect cognitive processing load has not been investigated yet. In the current study, three experiments investigated how the pupil dilation response is affected by prior knowledge of target speech location, target speech onset, and who is going to talk. A total of 56 young adults with normal hearing participated. They had to reproduce a target sentence presented to one ear while ignoring a distracting sentence simultaneously presented to the other ear. The two sentences were independently masked by fluctuating noise. Target location (left or right ear), speech onset, and talker variability were manipulated in separate experiments by keeping these features either fixed during an entire block or randomized over trials. Pupil responses were recorded during listening and performance was scored after recall. The results showed an improvement in performance when the location of the target speech was fixed instead of randomized. Additionally, location uncertainty increased the pupil dilation response, which suggests that prior knowledge of location reduces cognitive load. Interestingly, the observed pupil responses for each condition were consistent with subjective reports of listening effort. We conclude that communicating in a dynamic environment like a cocktail party (where participants in competing conversations move unpredictably) requires substantial listening effort because of the demands placed on attentional processes. (C) 2015 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

  • 22.
    Koelewijn, Thomas
    et al.
    Vrije University of Amsterdam, Netherlands Vrije University of Amsterdam, Netherlands .
    Shinn-Cunningham, Barbara G.
    Boston University, MA 02215 USA .
    Zekveld, Adriana
    Linköping University, Department of Behavioural Sciences and Learning, Disability Research. Linköping University, Faculty of Arts and Sciences.
    Kramer, Sophia E.
    Vrije University of Amsterdam, Netherlands Vrije University of Amsterdam, Netherlands .
    The pupil response is sensitive to divided attention during speech processing2014In: Hearing Research, ISSN 0378-5955, E-ISSN 1878-5891, Vol. 312, p. 114-120Article in journal (Refereed)
    Abstract [en]

    Dividing attention over two streams of speech strongly decreases performance compared to focusing on only one. How divided attention affects cognitive processing load as indexed with pupillometry during speech recognition has so far not been investigated. In 12 young adults the pupil response was recorded while they focused on either one or both of two sentences that were presented dichotically and masked by fluctuating noise across a range of signal-to-noise ratios. In line with previous studies, the performance decreases when processing two target sentences instead of one. Additionally, dividing attention to process two sentences caused larger pupil dilation and later peak pupil latency than processing only one. This suggests an effect of attention on cognitive processing load (pupil dilation) during speech processing in noise.

  • 23.
    Koelewijn, Thomas
    et al.
    Vrije Univ Amsterdam, Netherlands.
    Zekveld, Adriana A.
    Vrije Univ Amsterdam, Netherlands.
    Lunner, Thomas
    Linköping University, Department of Behavioural Sciences and Learning, Disability Research. Linköping University, Faculty of Arts and Sciences. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, The Swedish Institute for Disability Research. Linköping University, Department of Clinical and Experimental Medicine, Division of Speech language pathology, Audiology and Otorhinolaryngology. Eriksholm Res Ctr, Denmark; Tech Univ Denmark, Denmark.
    Kramer, Sophia E.
    Vrije Univ Amsterdam, Netherlands.
    The effect of reward on listening effort as reflected by the pupil dilation response2018In: Hearing Research, ISSN 0378-5955, E-ISSN 1878-5891, Vol. 367, p. 106-112Article in journal (Refereed)
    Abstract [en]

    Listening to speech in noise can be effortful but when motivated people seem to be more persevering. Previous research showed effects of monetary reward on autonomic responses like cardiovascular reactivity and pupil dilation while participants processed auditory information. The current study examined the effects of monetary reward on the processing of speech in noise and related listening effort as reflected by the pupil dilation response. Twenty-four participants (median age 21 yrs) performed two speech reception threshold (SRT) tasks, one tracking 50% correct (hard) and one tracking 85% correct (easy), both of which they listened to and repeated sentences uttered by a female talker. The sentences were presented with a single male talker or, in a control condition, in quiet. Participants were told that they could earn a high (5 euros) or low (0.20 euro) reward when repeating 70% or more of the sentences correctly. Conditions were presented in a blocked fashion and during each trial, pupil diameter was recorded. At the end of each block, participants rated the effort they had experienced, their performance, and their tendency to quit listening. Additionally, participants performed a working memory capacity task and filled in a need-for-recovery questionnaire as these tap into factors that influence the pupil dilation response. The results showed no effect of reward on speech perception performance as reflected by the SRT. The peak pupil dilation showed a significantly larger response for high than for low reward, for the easy and hard conditions, but not the control condition. Higher need for recovery was associated with a higher subjective tendency to quit listening. Consistent with the Framework for Understanding Effortful Listening, we conclude that listening effort as reflected by the peak pupil dilation is sensitive to the amount of monetary reward. (C) 2018 The Authors. Published by Elsevier B.V.

  • 24.
    Kundu, Soumi
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Cancer and Vascular Biology.
    Munjal, Charu
    Tyagi, Neetu
    Sen, Utpal
    Tyagi, Aaron C.
    Tyagi, Suresh C.
    Folic acid improves inner ear vascularization in hyperhomocysteinemic mice2012In: Hearing Research, ISSN 0378-5955, E-ISSN 1878-5891, Vol. 284, no 1-2, p. 42-51Article in journal (Refereed)
    Abstract [en]

    More than 29 million adults in the United States have been diagnosed with hearing loss. Interestingly, elevated homocysteine (Hcy) levels, known as hyperhomocysteinemia (HHcy), are also associated with impaired hearing. However, the associated mechanism remains obscure. The collagen receptor such as discoidin domain receptor 1 and matrix metalloproteinase (MMP) play a significant role in inner ear structure and function. We hypothesize that HHcy increases hearing thresholds by compromise in inner ear vasculature resulted from impaired Hcy metabolism, increased oxidative stress, collagen IVa and collagen Ia turnover. The treatment with folic acid (FA) protects elevated hearing thresholds and prevents reduction in vessel density by lowering abundant collagen deposition and oxidative stress in inner ear. To test this hypothesis we employed 8 weeks old male wild type (WT), cystathionine-beta-synthase heterozygote knockout (CBS+/-) mice, WT + FA (0.0057 mu g/g/day, equivalent to a 400 mu g/70 kg/day human dose in drinking water); and CBS(+/-) +FA. The mice were treated for four weeks. The hearing thresholds were determined by recording the auditory brainstem responses. Integrity of vessels was analyzed by perfusion of horseradish peroxidase (HRP) tracer. Endothelial permeability was assessed, which indicated restoration of HRP leakage by FA treatment. A total Hcy level was increased in stria vascularis (SV) and spiral ligament (SL) of CBS+/- mice which was lowered by FA. Interestingly, FA treatment lowered Col IVa Immunostaining by affecting its turnover. The levels of MMP-2, -9, methylenetetrahydrofolate reductase (MTHFR) and cystathione gamma lyase (CSE) were measured by Western blot analysis. The oxidative stress was high in SV and SL of CBS+/- compared to WT however the treatment with FA lowered oxidative stress in CBS+/- mice. These data suggested that hearing loss in CBS+/- mice was primarily due to leakage in inner ear circulation, also partly by induced collagen imbalance, increase in Hcy and oxidative stress in inner ear.

  • 25.
    Kytovuori, Laura
    et al.
    Oulu University Hospital, Finland; University of Oulu, Finland; University of Oulu, Finland; Oulu University Hospital, Finland.
    Hannula, Samuli
    Oulu University Hospital, Finland; University of Oulu, Finland; Oulu University Hospital, Finland; University of Oulu, Finland.
    Mäki-Torkko, Elina
    Linköping University, Department of Clinical and Experimental Medicine, Division of Speech language pathology, Audiology and Otorhinolaryngology. Linköping University, Faculty of Medicine and Health Sciences. Oulu University Hospital, Finland.
    Sorri, Martti
    Oulu University Hospital, Finland; University of Oulu, Finland; Oulu University Hospital, Finland; University of Oulu, Finland.
    Majamaa, Kari
    Oulu University Hospital, Finland; University of Oulu, Finland; University of Oulu, Finland; Oulu University Hospital, Finland.
    A nonsynonymous mutation in the WFS1 gene in a Finnish family with age-related hearing impairment2017In: Hearing Research, ISSN 0378-5955, E-ISSN 1878-5891, Vol. 355, p. 97-101Article in journal (Refereed)
    Abstract [en]

    Wolfram syndrome (WS) is caused by recessive mutations in the Wolfram syndrome 1 (WFS1) gene. Sensorineural hearing impairment (HI) is a frequent feature in WS and, furthermore, certain mutations in WFS1 cause nonsyndromic dominantly inherited low-frequency sensorineural HI. These two phenotypes are clinically distinct indicating that WFS1 is a reasonable candidate for genetic studies in patients with other phenotypes of HI. Here we have investigated, whether the variation in WFS1 has a pathogenic role in age-related hearing impairment (ARHI). WFS1 gene was investigated in a population sample of 518 Finnish adults born in 1938-1949 and representing variable hearing phenotypes. Identified variants were evaluated with respect to pathogenic potential. A rare mutation predicted to be pathogenic was found in a family with many members with impaired hearing. Twenty members were recruited to a segregation study and a detailed clinical examination. Heterozygous p.Tyr528His variant segregated completely with late-onset HI in which hearing deteriorated first at high frequencies and progressed to mid and low frequencies later in life. We report the first mutation in the WFS1 gene causing late-onset HI with audiogram configurations typical for ARHI. Monogenic forms of ARHI are rare and our results add WFS1 to the short list of such genes. (C) 2017 Elsevier B.V. All rights reserved.

  • 26.
    Kytövuori, Laura
    et al.
    Medical Research Center Oulu, Oulu University Hospital, University of Oulu, Oulu, Finland; Research Unit of Clinical Neuroscience, University of Oulu, Oulu, Finland; Department of Neurology, Oulu University Hospital, Oulu, Finland.
    Hannula, Samuli
    Medical Research Center Oulu, Oulu University Hospital, University of Oulu, Oulu, Finland; Department of Otorhinolaryngology and Head and Neck Surgery, Oulu University Hospital, Oulu, Finland; PEDEGO Research Unit, University of Oulu, Oulu, Finland.
    Mäki-Torkko, Elina
    Department of Otorhinolaryngology and Head and Neck Surgery, Oulu University Hospital, Oulu, Finland; Department of Clinical and Experimental Medicine/Technical Audiology, Faculty of Health Sciences, Linköping University, Linköping, Sweden; Department of ENT-Head Neck Surgery, Region Östergötland, Linköping, Sweden.
    Sorri, Martti
    Medical Research Center Oulu, Oulu University Hospital, University of Oulu, Oulu, Finland; Department of Otorhinolaryngology and Head and Neck Surgery, Oulu University Hospital, Oulu, Finland; PEDEGO Research Unit, University of Oulu, Oulu, Finland.
    Majamaa, Kari
    Medical Research Center Oulu, Oulu University Hospital, University of Oulu, Oulu, Finland; Research Unit of Clinical Neuroscience, University of Oulu, Oulu, Finland; Department of Neurology, Oulu University Hospital, Oulu, Finland.
    A nonsynonymous mutation in the WFS1 gene in a Finnish family with age-related hearing impairment2017In: Hearing Research, ISSN 0378-5955, E-ISSN 1878-5891, Vol. 355, p. 97-101Article in journal (Refereed)
    Abstract [en]

    Wolfram syndrome (WS) is caused by recessive mutations in the Wolfram syndrome 1 (WFS1) gene. Sensorineural hearing impairment (HI) is a frequent feature in WS and, furthermore, certain mutations in WFS1 cause nonsyndromic dominantly inherited low-frequency sensorineural HI. These two phenotypes are clinically distinct indicating that WFS1 is a reasonable candidate for genetic studies in patients with other phenotypes of HI. Here we have investigated, whether the variation in WFS1 has a pathogenic role in age-related hearing impairment (ARHI). WFS1 gene was investigated in a population sample of 518 Finnish adults born in 1938-1949 and representing variable hearing phenotypes. Identified variants were evaluated with respect to pathogenic potential. A rare mutation predicted to be pathogenic was found in a family with many members with impaired hearing. Twenty members were recruited to a segregation study and a detailed clinical examination. Heterozygous p.Tyr528His variant segregated completely with late-onset HI in which hearing deteriorated first at high frequencies and progressed to mid and low frequencies later in life. We report the first mutation in the WFS1 gene causing late-onset HI with audiogram configurations typical for ARHI. Monogenic forms of ARHI are rare and our results add WFS1 to the short list of such genes.

  • 27.
    Liu, Wei
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Boström, Marja
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Plastic Surgery.
    Kinnefors, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Rask-Andersen, Helge
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Unique expression of connexins in the human cochlea2009In: Hearing Research, ISSN 0378-5955, E-ISSN 1878-5891, Vol. 250, no 1-2, p. 55-62Article in journal (Refereed)
    Abstract [en]

    Mutations in the genes GJB2 and GJB6, which encode the proteins Connexin 26 (Cx26) and Connexin 30 (Cx30), have been linked to nonsyndromic prelingual deafness in humans. These proteins may form so-called gap junctions (GJ) or transcellular pathways between cells. The pathogenesis of deafness due to GJ Connexin mutations remains unclear partly because examinations performed in the human ear are infrequent. Here we analysed the expression and distribution of Cx26 and Cx30 in five fresh normal human cochleae taken out at occasional surgery. Immunohistochemistry including confocal microscopy in decalcified specimen showed that these proteins are widely expressed in the human cochlea. In the lateral wall there was strong antibody co-labeling for Cx26 and Cx30 that support the existence of channels comprising heteromeric Cx26/Cx30 connexons. In the organ of Corti there were some co-labeling in the supporting cell area including mainly the Claudius cells and Deiter cells of these two Cxs, apart from isolated Cx26 and Cx30 labeling in the same area, suggestive of both homomeric/homotypic pattern and hybrid pattern (heteromeric or heterotypic). Cx30, Cx26 and Connexin 36 (Cx36) immunoreactivity was also associated with spiral ganglion type I neurons, the latter being a gap junction protein specific to neurons. Gap-junction-based electrical synapses are not known to occur in mammalian auditory system other than in bats where they may play a role for fast electrical nerve transmission useful for echolocation. Their potential role in the processing of human auditory nerve signaling as well as non-GJ roles of the connexins in human cochlea is discussed.

  • 28.
    Nilsson, Mats E.
    et al.
    Stockholm University, Faculty of Social Sciences, Department of Psychology, Perception and psychophysics.
    Schenkman, Bo N.
    Blind people are more sensitive than sighted people to binaural sound-location cues, particularly inter-aural level differences2016In: Hearing Research, ISSN 0378-5955, E-ISSN 1878-5891, Vol. 332, p. 223-232Article in journal (Refereed)
    Abstract [en]

    Blind people use auditory information to locate sound sources and sound-reflecting objects (echolocation). Sound source localization benefits from the hearing system's ability to suppress distracting sound reflections, whereas echolocation would benefit from “unsuppressing” these reflections. To clarify how these potentially conflicting aspects of spatial hearing interact in blind versus sighted listeners, we measured discrimination thresholds for two binaural location cues: inter-aural level differences (ILDs) and inter-aural time differences (ITDs). The ILDs or ITDs were present in single clicks, in the leading component of click pairs, or in the lagging component of click pairs, exploiting processes related to both sound source localization and echolocation. We tested 23 blind (mean age = 54 y), 23 sighted-age-matched (mean age = 54 y), and 42 sighted-young (mean age = 26 y) listeners. The results suggested greater ILD sensitivity for blind than for sighted listeners. The blind group's superiority was particularly evident for ILD-lag-click discrimination, suggesting not only enhanced ILD sensitivity in general but also increased ability to unsuppress lagging clicks. This may be related to the blind person's experience of localizing reflected sounds, for which ILDs may be more efficient than ITDs. On the ITD-discrimination tasks, the blind listeners performed better than the sighted age-matched listeners, but not better than the sighted young listeners. ITD sensitivity declines with age, and the equal performance of the blind listeners compared to a group of substantially younger listeners is consistent with the notion that blind people's experience may offset age-related decline in ITD sensitivity.

  • 29. Nilsson, Mats E.
    et al.
    Schenkman, Bo N.
    KTH, School of Computer Science and Communication (CSC), Speech, Music and Hearing, TMH. Université Catholique de Louvain, Belgium.
    Blind people are more sensitive than sighted people to binaural sound-location cues, particularly inter-aural level differences2016In: Hearing Research, ISSN 0378-5955, E-ISSN 1878-5891, Vol. 332, p. 223-232Article in journal (Refereed)
    Abstract [en]

    Blind people use auditory information to locate sound sources and sound-reflecting objects (echolocation). Sound source localization benefits from the hearing system's ability to suppress distracting sound reflections, whereas echolocation would benefit from "unsuppressing" these reflections. To clarify how these potentially conflicting aspects of spatial hearing interact in blind versus sighted listeners, we measured discrimination thresholds for two binaural location cues: inter-aural level differences (ILDs) and inter-aural time differences (ITDs). The ILDs or ITDs were present in single clicks, in the leading component of click pairs, or in the lagging component of click pairs, exploiting processes related to both sound source localization and echolocation. We tested 23 blind (mean age = 54 y), 23 sighted-age matched (mean age = 54 y), and 42 sighted-young (mean age = 26 y) listeners. The results suggested greater ILD sensitivity for blind than for sighted listeners. The blind group's superiority was particularly evident for ILD-lag-click discrimination, suggesting not only enhanced ILD sensitivity in general but also increased ability to unsuppress lagging clicks. This may be related to the blind person's experience of localizing reflected sounds, for which ILDs may be more efficient than ITDs. On the ITD-discrimination tasks, the blind listeners performed better than the sighted age-matched listeners, but not better than the sighted young listeners. ITD sensitivity declines with age, and the equal performance of the blind listeners compared to a group of substantially younger listeners is consistent with the notion that blind people's experience may offset age-related decline in ITD sensitivity.

  • 30. Nuttall, Alfred L
    et al.
    Fridberger, Anders
    Karolinska Institutet, Stockholm, Sweden.
    Instrumentation for studies of cochlear mechanics: from von Békésy forward2012In: Hearing Research, ISSN 0378-5955, E-ISSN 1878-5891, Vol. 293, no 1-2, p. 3-11Article in journal (Refereed)
    Abstract [en]

    Georg von Békésy designed the instruments needed for his research. He also created physical models of the cochlea allowing him to manipulate the parameters (such as volume elasticity) that could be involved in controlling traveling waves. This review is about the specific devices that he used to study the motion of the basilar membrane thus allowing the analysis that lead to his Nobel Prize Award. The review moves forward in time mentioning the subsequent use of von Békésy's methods and later technologies important for motion studies of the organ of Corti. Some of the seminal findings and the controversies of cochlear mechanics are mentioned in relation to the technical developments.

  • 31.
    Ohlenforst, Barbara
    et al.
    Vrije Univ Amsterdam, Netherlands; Amsterdam Publ Hlth Res Inst, Netherlands; Oticon AS, Denmark.
    Wendt, Dorothea
    Oticon AS, Denmark; Tech Univ Denmark, Denmark.
    Kramer, Sophia E.
    Vrije Univ Amsterdam, Netherlands; Amsterdam Publ Hlth Res Inst, Netherlands.
    Naylor, Graham
    MRC CSO Inst Hearing Res, Scotland; Univ Nottingham, England.
    Zekveld, Adriana
    Linköping University, Department of Behavioural Sciences and Learning. Linköping University, Faculty of Arts and Sciences. Linköping University, The Swedish Institute for Disability Research. Vrije Univ Amsterdam, Netherlands; Amsterdam Publ Hlth Res Inst, Netherlands; Orebro Univ, Sweden.
    Lunner, Thomas
    Linköping University, Department of Behavioural Sciences and Learning, Disability Research. Linköping University, Faculty of Arts and Sciences. Linköping University, The Swedish Institute for Disability Research. Orebro Univ, Sweden; Oticon AS, Denmark; Tech Univ Denmark, Denmark.
    Impact of SNR, masker type and noise reduction processing on sentence recognition performance and listening effort as indicated by the pupil dilation response2018In: Hearing Research, ISSN 0378-5955, E-ISSN 1878-5891, Vol. 365, p. 90-99Article in journal (Refereed)
    Abstract [en]

    Recent studies have shown that activating the noise reduction scheme in hearing aids results in a smaller peak pupil dilation (PPD), indicating reduced listening effort, at 50% and 95% correct sentence recognition with a 4-talker masker. The objective of this study was to measure the effect of the noise reduction scheme (on or off) on PPD and sentence recognition across a wide range of signal-to-noise ratios (SNRs) from +16 dB to -12 dB and two masker types (4-talker and stationary noise). Relatively low PPDs were observed at very low (-12 dB) and very high (+16 dB to +8 dB) SNRs presumably due to giving up and easy listening, respectively. The maximum PPD was observed with SNRs at approximately 50% correct sentence recognition. Sentence recognition with both masker types was significantly improved by the noise reduction scheme, which corresponds to the shift in performance from SNR function at approximately 5 dB toward a lower SNR. This intelligibility effect was accompanied by a corresponding effect on the PPD, shifting the peak by approximately 4 dB toward a lower SNR. In addition, with the 4-talker masker, when the noise reduction scheme was active, the PPD was smaller overall than that when the scheme was inactive. We conclude that with the 4-talker masker, noise reduction scheme processing provides a listening effort benefit in addition to any effect associated with improved intelligibility. Thus, the effect of the noise reduction scheme on listening effort incorporates more than can be explained by intelligibility alone, emphasizing the potential importance of measuring listening effort in addition to traditional speech reception measures. (C) 2018 Elsevier B.V. All rights reserved.

  • 32.
    Ohlenforst, Barbara
    et al.
    Vrije University of Amsterdam, Netherlands; Amsterdam Public Health Research Institute, Netherlands; Oticon AS, Denmark.
    Zekveld, Adriana
    Linköping University, Department of Behavioural Sciences and Learning. Linköping University, The Swedish Institute for Disability Research. Linköping University, Faculty of Arts and Sciences. Vrije University of Amsterdam, Netherlands; Amsterdam Public Health Research Institute, Netherlands.
    Lunner, Thomas
    Linköping University, Department of Behavioural Sciences and Learning, Disability Research. Linköping University, Faculty of Arts and Sciences. Linköping University, The Swedish Institute for Disability Research. Oticon AS, Denmark.
    Wendt, Dorothea
    Oticon AS, Denmark; Technical University of Denmark, Denmark.
    Naylor, Graham
    MRC CSO Institute Hearing Research, Scotland.
    Wang, Yang
    Vrije University of Amsterdam, Netherlands; Amsterdam Public Health Research Institute, Netherlands; Oticon AS, Denmark.
    Versfeld, Niek J.
    Vrije University of Amsterdam, Netherlands; Amsterdam Public Health Research Institute, Netherlands.
    Kramer, Sophia E.
    Vrije University of Amsterdam, Netherlands; Amsterdam Public Health Research Institute, Netherlands.
    Impact of stimulus-related factors and hearing impairment on listening effort as indicated by pupil dilation2017In: Hearing Research, ISSN 0378-5955, E-ISSN 1878-5891, Vol. 351, p. 68-79Article in journal (Refereed)
    Abstract [en]

    Previous research has reported effects of masker type and signal-to-noise ratio (SNR) on listening effort, as indicated by the peak pupil dilation (PPD) relative to baseline during speech recognition. At about 50% correct sentence recognition performance, increasing SNRs generally results in declining PPDs, indicating reduced effort. However, the decline in PPD over SNRs has been observed to be less pronounced for hearing-impaired (HI) compared to normal-hearing (NH) listeners. The presence of a competing talker during speech recognition generally resulted in larger PPDs as compared to the presence of a fluctuating or stationary background noise. The aim of the present study was to examine the interplay between hearing-status, a broad range of SNRs corresponding to sentence recognition performance varying from 0 to 100% correct, and different masker types (stationary noise and single-talker masker) on the PPD during speech perception. Twenty-five HI and 32 age-matched NH participants listened to sentences across a broad range of SNRs, masked with speech from a single talker (-25 dB to +15 dB SNR) or with stationary noise (-12 dB to +16 dB). Correct sentence recognition scores and pupil responses were recorded during stimulus presentation. With a stationary masker, NH listeners show maximum PPD across a relatively narrow range of low SNRs, while HI listeners show relatively large PPD across a wide range of ecological SNRs. With the single-talker masker, maximum PPD was observed in the mid-range of SNRs around 50% correct sentence recognition performance, while smaller PPDs were observed at lower and higher SNRs. Mixed-model ANOVAs revealed significant interactions between hearing-status and SNR on the PPD for both masker types. Our data show a different pattern of PPDs across SNRs between groups, which indicates that listening and the allocation of effort during listening in daily life environments may be different for NH and HI listeners. (C) 2017 The Authors. Published by Elsevier B.V.

  • 33. Palmgren, Bjorn
    et al.
    Jin, Zhe
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Ma, Hongmin
    Jiao, Yu
    Olivius, Petri
    beta-Bungarotoxin application to the round window: An in vivo deafferentation model of the inner ear2010In: Hearing Research, ISSN 0378-5955, E-ISSN 1878-5891, Vol. 265, no 1-2, p. 70-76Article in journal (Refereed)
    Abstract [en]

    Hearing impairment can be caused by a primary lesion to the spiral ganglion neurons (SGNs) with the hair cells kept intact, for example via tumours, trauma or auditory neuropathy. To mimic these conditions in animal models various methods of inflicting damage to the inner ear have been used. However, only a few methods have a selective effect on the SGNs, which is of importance since it might be clinically more relevant to study hearing impairment with the hair cells undamaged. beta-Bungarotoxin is a venom of the Taiwan banded krait, which in vitro has been shown to induce apoptosis in neurons, leaving remaining cochlear cells intact. We wanted to create an in vivo rat model of selective damage to primary auditory neurons. Under deep anaesthesia, 41 rats received beta-Bungarotoxin or saline to the round window niche. At postoperative intervals between days 3 and 21 auditory brainstem response (ABR) measurement, immunohistochemistry, SGN quantification and cochlear surface preparation were performed. The results in the beta-Bungarotoxin-treated ears, as compared with sham-operated ears, show significantly increased ABR thresholds at all postoperative intervals, illustrating a severe to profound hearing loss at all tested frequencies (3.5, 7, 16 and 28 kHz). Quantification of the SGNs showed no obvious reduction in neuronal numbers until 14 days postoperatively. Between days 14 and 21 a significant reduction in SGN numbers was observed. Cochlear surface preparation and immunohistochemistry showed that the hair cells were intact. Our results illustrate that in vivo application of beta-Bungarotoxin to the round window niche is a feasible way of deafening rats by SGN reduction while the hair cells are kept intact. (C) 2010 Elsevier B.V. All rights reserved.

  • 34.
    Palmgren, Björn
    et al.
    Karolinska University Hospital, Stockholm, Sweden.
    Jin, Zhe
    Uppsala University, Sweden .
    Ma, Hongmin
    Karolinska University Hospital, Stockholm, Sweden.
    Jiao, Yu
    Karolinska University Hospital, Stockholm, Sweden.
    Olivius, Petri
    Karolinska University Hospital, Stockholm, Sweden.
    β-Bungarotoxin application to the round window: An in vivo deafferentation model of the inner ear2010In: Hearing Research, ISSN 0378-5955, E-ISSN 1878-5891, Vol. 265, no 1-2, p. 70-76Article in journal (Refereed)
    Abstract [en]

    Hearing impairment can be caused by a primary lesion to the spiral ganglion neurons (SGNs) with the hair cells kept intact, for example via tumours, trauma or auditory neuropathy. To mimic these conditions in animal models various methods of inflicting damage to the inner ear have been used. However, only a few methods have a selective effect on the SGNs, which is of importance since it might be clinically more relevant to study hearing impairment with the hair cells undamaged. beta-Bungarotoxin is a venom of the Taiwan banded krait, which in vitro has been shown to induce apoptosis in neurons, leaving remaining cochlear cells intact. We wanted to create an in vivo rat model of selective damage to primary auditory neurons. Under deep anaesthesia, 41 rats received beta-Bungarotoxin or saline to the round window niche. At postoperative intervals between days 3 and 21 auditory brainstem response (ABR) measurement, immunohistochemistry, SGN quantification and cochlear surface preparation were performed. The results in the beta-Bungarotoxin-treated ears, as compared with sham-operated ears, show significantly increased ABR thresholds at all postoperative intervals, illustrating a severe to profound hearing loss at all tested frequencies (3.5, 7, 16 and 28 kHz). Quantification of the SGNs showed no obvious reduction in neuronal numbers until 14 days postoperatively. Between days 14 and 21 a significant reduction in SGN numbers was observed. Cochlear surface preparation and immunohistochemistry showed that the hair cells were intact. Our results illustrate that in vivo application of beta-Bungarotoxin to the round window niche is a feasible way of deafening rats by SGN reduction while the hair cells are kept intact.

  • 35.
    Peacock, John
    et al.
    Univ Antwerp, Lab Biomed Phys, Groenenborgerlaan 171, B-2020 Antwerp, Belgium..
    Dirckx, Joris
    Univ Antwerp, Lab Biomed Phys, Groenenborgerlaan 171, B-2020 Antwerp, Belgium..
    von Unge, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland. Akershus Univ Hosp, Dept Otorhinolaryngol, Oslo, Norway.;Univ Oslo, Oslo, Norway..
    Intraoperative assessment of ossicular fixation2016In: Hearing Research, ISSN 0378-5955, E-ISSN 1878-5891, Vol. 340, p. 99-106Article in journal (Refereed)
    Abstract [en]

    Determining the degree of ossicular fixation is a difficult task, with the final assessment often being made with manual palpation during exploratory tympanotomy. A more objective method to evaluate ossicular fixation would be valuable. In this paper we describe a new method which makes use of a magnet and coil to measure ossicular motion through the ear canal with an elevated tympanic membrane. We report measurements of the vibration response at the umbo, the tip of the incus long process and the lateral posterior crus of the stapes before and after artificially fixing the stapes footplate and anterior mallear ligament with luting cement. Results were obtained on temporal bones, but the practicality of the method allows easy clinical implementation. Velocity ratios between different measurement points along the ossicular chain may provide a quantitative indication of the degree of stapes fixation. Isolated anterior mallear ligament fixation was not distinguishable from the unfixed condition.

  • 36.
    Rask-Andersen, Helge
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Boström, Marja
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Gerdin, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Kinnefors, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Nyberg, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience. Neurokirurgi.
    Engstrand, Thomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Miller, Josef M.
    Lindholm, Dan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Regeneration of human auditory nerve. In vitro/in video demonstration of neural progenitor cells in adult human and guinea pig spiral ganglion2005In: Hearing Research, ISSN 0378-5955, E-ISSN 1878-5891, Vol. 203, no 1-2, p. 180-191Article in journal (Refereed)
    Abstract [en]

    Time lapse video recordings of cultured adult human and guinea pig spiral ganglion (hSG and gpSG) show that mitogen responsive progenitor/stem cells develop in the form of spheres that proliferate and differentiate into mature neurons and glia cells. Neurospheres, cultured with EGF and bFGF showed expression of nestin and incorporation of 5'-Bromo-2-deoxyuridine (BrdU). Newly formed BrdU labelled cells were positive for beta-tubulin, and also for GFAP demonstrating that neuronal cells were derived from a dividing population of progenitor cells. Dissociated spheres cultured either with glia cell line-derived neurotrophic factor (GDNF) or brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3), induced differentiation of the progenitor cells. Video microscopy showed that neurons develop from subcultured spheres maintained for up to four weeks. Neurons showed fasciculation and migration with a speed of 10-30 microm/h, and some cells had up to 6 mm long neurites coexpressing TrkB and TrkC receptors. Precise dissection suggests that the neurons formed are cochlea-specific. The results suggest that the mammalian auditory nerve has the capability for self-renewal and replacement. Transplantation of progenitor cells together with established means to induce neural differentiation and fiber growth may facilitate strategies for better repair and treatment of auditory neuronal damage.

  • 37.
    Reinfeldt, Sabine
    et al.
    Chalmers University of Technology, Göteborg, Sweden.
    Stenfelt, Stefan
    Linköping University, Department of Clinical and Experimental Medicine, Technical Audiology. Linköping University, Faculty of Health Sciences.
    Håkansson, Bo
    Chalmers University of Technology, Göteborg, Sweden.
    Estimation of bone conduction skull transmission by hearing thresholds and ear-canal sound pressure2013In: Hearing Research, ISSN 0378-5955, E-ISSN 1878-5891, Vol. 299, p. 19-28Article in journal (Refereed)
    Abstract [en]

    Bone conduction sound transmission in the human skull and the occlusion effect were estimated from hearing thresholds and ear-canal sound pressure (ECSP) measured by a probe tube microphone when stimulation was at three positions on the skull (ipsilateral mastoid, contralateral mastoid, and forehead). The measurements were done with the ear-canal open as well as occluded by an ear-plug. Depending on the estimation method, transcranial transmission at frequencies below 1 kHz was between −8 and 5 dB, around 0 dB at 1 kHz that decreased with frequency to between −17 and −7 dB at 8 kHz. The forehead transmission was, except at frequencies between 1 and 2 kHz, similar to that proposed in the standard ISO:389-3 (1994) when the threshold measurements were conducted with open ear-canals. Compared with the same measurements using hearing thresholds, the ECSP gave similar transmission results at most frequencies, but differed at 0.5, 0.75, 2 and 3 kHz. One probable reason for the differences between thresholds and ECSP might be a significant perception improvement (lower thresholds) when the stimulation was at the ipsilateral mastoid that was not found at the other positions. This improvement, which also was present in the occlusion effect data, was hypothesized to originate in greater sensitivity of the cochlea for vibration in line with the ipsilateral stimulation direction than from other directions.

  • 38.
    Sim, J. H.
    et al.
    University of Zurich Hospital, Switzerland; University of Zurich, Switzerland.
    Dobrev, I.
    University of Zurich Hospital, Switzerland; University of Zurich, Switzerland.
    Gerig, R.
    University of Zurich Hospital, Switzerland; University of Zurich, Switzerland.
    Pfiffner, F.
    University of Zurich Hospital, Switzerland; University of Zurich, Switzerland.
    Stenfelt, Stefan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Huber, A. M.
    University of Zurich Hospital, Switzerland; University of Zurich, Switzerland.
    Roosli, C.
    University of Zurich Hospital, Switzerland; University of Zurich, Switzerland.
    Interaction between osseous and non-osseous vibratory stimulation of the human cadaveric head2016In: Hearing Research, ISSN 0378-5955, E-ISSN 1878-5891, Vol. 340, p. 153-160Article in journal (Refereed)
    Abstract [en]

    Bone conduction (BC) stimulation can be applied by vibration to the bony or skin covered skull (osseous BC), or on soft tissue such as the neck (non-osseous BC). The interaction between osseous and non osseous bone conduction pathways is assessed in this study. The relation between bone vibrations measured at the cochlear promontory and the intracranial sound pressure for stimulation directly on the dura and for stimulation at the mastoid between 0.2 and 10 kHz was compared. First, for stimulation on the dura, varying the static coupling force of the BC transducer on the dura had only a small effect on promontory vibration. Second, the presence or absence of intracranial fluid did not affect promontory vibration for stimulation on the dura. Third, stimulation on the mastoid elicited both promontory vibration and intracranial sound pressure. Stimulation on the dura caused intracranial sound pressure to a similar extent above 0.5 kHz compared to stimulation on the mastoid, while promontory vibration was less by 20-40 dB. From these findings, we conclude that intracranial sound pressure (non-osseous BC) only marginally affects bone vibrations measured on the promontory (osseous BC), whereas skull vibrations affect intracranial sound pressure. (C) 2016 Elsevier B.V. All rights reserved.

  • 39.
    Stenfelt, Stefan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Inner ear contribution to bone conduction hearing in the human2015In: Hearing Research, ISSN 0378-5955, E-ISSN 1878-5891, Vol. 329, p. 41-51Article, review/survey (Refereed)
    Abstract [en]

    Bone conduction (BC) hearing relies on sound vibration transmission in the skull bone. Several clinical findings indicate that in the human, the skull vibration of the inner ear dominates the response for BC sound. Two phenomena transform the vibrations of the skull surrounding the inner ear to an excitation of the basilar membrane, (1) inertia of the inner ear fluid and (2) compression and expansion of the inner ear space. The relative importance of these two contributors were investigated using an impedance lumped element model. By dividing the motion of the inner ear boundary in common and differential motion it was found that the common motion dominated at frequencies below 7 kHz but above this frequency differential motion was greatest. When these motions were used to excite the model it was found that for the normal ear, the fluid inertia response was up to 20 dB greater than the compression response. This changed in the pathological ear where, for example, otosclerosis of the stapes depressed the fluid inertia response and improved the compression response so that inner ear compression dominated BC hearing at frequencies above 400 Hz. The model was also able to predict experimental and clinical findings of BC sensitivity in the literature, for example the so called Carhart notch in otosclerosis, increased BC sensitivity in superior semicircular canal dehiscence, and altered BC sensitivity following a vestibular fenestration and RW atresia. (C) 2014 Elsevier B.V. All rights reserved.

  • 40.
    Stenfelt, Stefan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Model predictions for bone conduction perception in the human2016In: Hearing Research, ISSN 0378-5955, E-ISSN 1878-5891, no 15, p. 30076-30079Article in journal (Refereed)
    Abstract [en]

    Five different pathways are often suggested as important for bone conducted (BC) sound: (1) sound pressure in the ear canal, (2) inertia of the middle ear ossicles, (3) inertia of the inner ear fluid, (4) compression of the inner ear space, and (5) pressure transmission from the skull interior. The relative importance of these pathways was investigated with an acoustic-impedance model of the inner ear. The model incorporated data of BC generated ear canal sound pressure, middle ear ossicle motion, cochlear promontory vibration, and intracranial sound pressure. With BC stimulation at the mastoid, the inner ear inertia dominated the excitation of the cochlea but inner ear compression and middle ear inertia were within 10 dB for almost the entire frequency range of 0.1-10 kHz. Ear canal sound pressure gave little contribution at the low and high frequencies, but was around 15 dB below the total contribution at the mid frequencies. Intracranial sound pressure gave responses similar to the others at low frequencies, but decreased with frequency to a level of 55 dB below the total contribution at 10 kHz. When the BC inner ear model was evaluated against AC stimulation at threshold levels, the results were close up to approximately 4 kHz but deviated significantly at higher frequencies.

  • 41.
    Stenfelt, Stefan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Technical Audiology.
    Simultaneous cancellation of air and bone conduction tones at two frequencies: Extension of the famous experiment by von Békésy2007In: Hearing Research, ISSN 0378-5955, E-ISSN 1878-5891, Vol. 225, no 1-2, p. 105-116Article in journal (Refereed)
    Abstract [en]

    Cancellation experiments between air conduction (AC) and bone conduction (BC) tones were conducted at two frequencies (0.7 and 1.1 kHz) and three levels (40, 50, and 60 dB HL) in three subjects. The tests were divided into three categories: (1) single tone cancellation, (2) simultaneous cancellation of two tones, and (3) cancellation of one tone while a disturbing tone was present. In total, each subject performed twelve cancellation tasks. The hypothesis is that the AC and BC sound transmission behaves as linear systems and they both excite the basilar membrane in the cochlea similarly. The cancellation results are presented as the deviations from this hypothesis, except for a few larger deviations, the intrasubject deviations were generally less than 0.5 dB and 5°. The results from all three test categories indicate that the hypothesis of linear transmission systems and similarity of cochlear stimulation by AC and BC holds. However, due to the subjects' limited ability to conduct optimal cancellation and to imperfect methodology and equipment, the small deviations from perfectly linear cancellation that were observed do neither conclusively prove nor refute the possibility of small differences in the cochlear processing of AC and BC sound. Nonetheless, it is clear that if such differences in the processing of the two stimuli exist, they are small in magnitude. © 2006 Elsevier B.V. All rights reserved.

  • 42.
    Stenfelt, Stefan
    et al.
    Chalmers University of Technology.
    Hato, N
    Stanford.
    Goode, RL
    Stanford.
    Round window membrane motion with air conduction and bone conduction stimulation2004In: Hearing Research, ISSN 0378-5955, E-ISSN 1878-5891, Vol. 198, no 02-Jan, p. 10-24Article in journal (Refereed)
    Abstract [en]

    The vibration patterns of the round window (RW) membrane in human cadaver temporal bone specimens were assessed by measurements of the velocity of reflective targets placed on the RW membrane with an approximate spacing of 0.2 mm. The velocity was measured in the frequency range 0.1-10 kHz by a laser Doppler vibrometer in four specimens with air conduction (AC) stimulation and in four specimens with bone conduction (BC) stimulation. The response pattern was investigated by analyzing the velocity response of all targets on the RW membrane, by making iso-amplitude and iso-phase contour plots of the membrane surface, and by creating animations of the surface vibration at several frequencies. Similar response pattern was found with AC and BC stimulations. At frequencies below 1.5 kHz, the RW membrane vibrates nearly as a whole in an in-and-out motion and above 1.5 kHz, the membrane moves primarily in two sections that vibrate with approximately 180degrees difference. Indication of some traveling wave motion of the RW membrane at those frequencies was also found. At higher frequencies, above 3 kHz, the membrane motion is complex with a mixture of modal and traveling wave motion. An increase of the stimulation level did not alter the vibration pattern; it only gave an increase of the RW membrane vibration amplitude corresponding to the increase in stimulation. When the mode of stimulation at the oval window was altered, by the insertion of a 0.6 mm piston, the vibration pattern of the RW membrane changed.

  • 43.
    Stenfelt, Stefan
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Technical Audiology . Linköping University, Faculty of Health Sciences.
    Håkansson, Bo
    Chalmers.
    Air versus bone conduction: An equal loudness investigation2002In: Hearing Research, ISSN 0378-5955, E-ISSN 1878-5891, Vol. 167, no 1-2, p. 1-12Article in journal (Refereed)
  • 44.
    Stenfelt, Stefan
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Technical Audiology . Linköping University, Faculty of Health Sciences.
    Puria, Sunil
    Stanford University.
    Hato, Naohito
    Stanford University.
    Goode, Richard
    Stanford university.
    Basilar membrane and osseous spiral lamina motion in human cadavers with air and bone conduction stimuli2004In: Hearing Research, ISSN 0378-5955, E-ISSN 1878-5891, Vol. 198, no 1-2, p. 10-24Article in journal (Refereed)
  • 45.
    Stenfelt, Stefan
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Technical Audiology. Linköping University, Faculty of Health Sciences.
    Zeitooni, Mehrnaz
    Linköping University, Department of Clinical and Experimental Medicine, Technical Audiology. Linköping University, Faculty of Health Sciences.
    Loudness functions with air and bone conduction stimulation in normal-hearing subjects using a categorical loudness scaling procedure2013In: Hearing Research, ISSN 0378-5955, E-ISSN 1878-5891, Vol. 301, p. 85-92Article in journal (Refereed)
    Abstract [en]

    In a previous study (Stenfelt and Håkansson, 2002) a loudness balance test between bone conducted (BC) sound and air conducted (AC) sound was performed at frequencies between 0.25 and 4 kHz and at levels corresponding to 30–80 dB HL. The main outcome of that study was that for maintaining equal loudness, the level increase of sound with BC stimulation was less than that of AC stimulation with a ratio between 0.8 and 0.93 dB/dB. However, because it was shown that AC and BC tone cancellation was independent of the stimulation level, the loudness level difference did not originate in differences in basilar membrane stimulation. Therefore, it was speculated that the result could be due to the loudness estimation procedure. To investigate this further, another loudness estimation method (adaptive categorical loudness scaling) was here employed in 20 normal-hearing subjects.

    The loudness of a low-frequency and a high-frequency noise burst was estimated using the adaptive categorical loudness scaling technique when the stimulation was bilaterally by AC or BC. The sounds where rated on an 11-point scale between inaudible and too loud. The total dynamic range for these sounds was over 80 dB when presented by AC (between inaudible and too loud) and the loudness functions were similar for the low and the high-frequency stimulation. When the stimulation was by BC the loudness functions were steeper and the ratios between the slopes of the AC and BC loudness functions were 0.88 for the low-frequency sound and 0.92 for the high-frequency sound. These results were almost equal to the previous published results using the equal loudness estimation procedure, and it was unlikely that the outcome stems from the loudness estimation procedure itself. One possible mechanism for the result was loudness integration of multi-sensory input. However, no conclusive evidence for such a mechanism could be given by the present study.

  • 46.
    Strömberg, Anna-Karin
    et al.
    Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Otorhinolaryngology in Linköping. Karolinska Hospital, Sweden.
    Olofsson, Åke
    Karolinska Institute, Sweden.
    Westin, Magnus
    Karolinska Hospital, Sweden.
    Duan, Maoli
    Karolinska Hospital, Sweden; Karolinska Institute Stockholm, Sweden.
    Stenfelt, Stefan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Changes in cochlear function related to acoustic stimulation of cervical vestibular evoked myogenic potential stimulation2016In: Hearing Research, ISSN 0378-5955, E-ISSN 1878-5891, Vol. 340, p. 43-49Article in journal (Refereed)
    Abstract [en]

    Evaluation of cervical evoked myogenic potentials (c-VEMP) is commonly applied in clinical investigations of patients with suspected neurotological symptoms. Short intense acoustic stimulation of peak levels close to 130 dB SPL is required to elicit the responses. A recent publication on bilateral significant sensorineural hearing loss related to extensive VEMP stimulation motivates evaluations of immediate effects on hearing acuity related to the intense acoustic stimulation required to elicit c-VEMP responses. The aim of the current study was to investigate changes in DPOAE-levels and hearing thresholds in relation to c-VEMP testing in humans. More specifically, the current focus is on immediate changes in hearing thresholds and changes in DPOAE-levels at frequencies 0.5 octaves above the acoustic stimulation when applying shorter tone bursts than previously used. Hearing acuity before and immediately after exposure to c-VEMP stimulation was examined in 24 patients with normal hearing referred for neurotologic testing. The stimulation consisted of 192 tonebursts of 6 ms and was presented at 500 Hz and 130 dB peSPL. Bekesy thresholds at 0.125-8 kHz and DPOAE I/O growth functions with stimulation at 0.75 and 3 kHz were used to assess c-VEMP related changes in hearing status. No significant deterioration in Bekesy thresholds was detected. Significant reduction in DPOAE levels at 0.75 (0.5-1.35 dB) and 3 kHz (1.6-2.1 dB) was observed after c-VEMP stimulation without concomitant changes in cochlear compression. The results indicated that there was no immediate audiometric loss related to c-VEMP stimulation in the current group of patients. The significant reduction of DPOAE levels at a wider frequency range than previously described after the c-VEMP test could be related to the stimulation with shorter tone bursts. The results show that c-VEMP stimulation causes reduction in DPOAE-levels at several frequencies that corresponds to half the reductions in DPOAE levels reported after exposure to the maximally allowed occupational noise for an 8 h working day. Consequently, extended stimuli intensity or stimulation repetition with c-VEMP testing should be avoided to reduce the risk for noise-induced cochlear injury.

  • 47.
    Takumida, Masaya
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Anniko, Matti
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Popa, Raul
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Zhang, De Ming
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Lipopolysaccharide-induced expression of inducible nitric oxide synthase in the guinea pig organ of Corti2000In: Hearing Research, ISSN 0378-5955, E-ISSN 1878-5891, Vol. 140, no 1-2, p. 91-8Article in journal (Refereed)
    Abstract [en]

    The purpose of the investigation was to ascertain whether inoculation of bacterial lipopolysaccharide (LPS) into the cochlea of the guinea pig could elicit formation of inducible nitric oxide synthase (iNOS). Immunohistochemical study revealed that immunoreactivity to iNOS was seen below outer hair cells representing nerve fibers and synaptic nerve endings. iNOS-staining could also be observed in phalangeal dendrites of Deiter's cells pointing to the cuticular membrane, Hensen's cells and on stria vascularis 48 h after inoculation with LPS. Immunohistochemical investigation with a specific anti-nitrotyrosine antibody also revealed intense immunoreactivity identical to that of iNOS, suggesting formation of peroxynitrite in the organ of Corti by the reaction of NO with O(2)(-). On the basis of these findings, it can be concluded that NO together with O(2)(-), which form the more reactive peroxynitrite, are the most important pathogenic agents in LPS-induced damage of cochlea in the guinea pig.

  • 48.
    Wendt, Dorothea
    et al.
    Eriksholm Res Ctr, Denmark; Tech Univ Denmark, Denmark.
    Koelewijn, Thomas
    Vrije Univ Amsterdam Med Ctr, Netherlands.
    Ksiazek, Patrycja
    Eriksholm Res Ctr, Denmark.
    Kramer, Sophia E.
    Vrije Univ Amsterdam Med Ctr, Netherlands.
    Lunner, Thomas
    Linköping University, Department of Behavioural Sciences and Learning, Disability Research. Linköping University, Faculty of Arts and Sciences. Linköping University, The Swedish Institute for Disability Research. Eriksholm Res Ctr, Denmark; Tech Univ Denmark, Denmark.
    Toward a more comprehensive understanding of the impact of masker type and signal-to-noise ratio on the pupillary response while performing a speech-in-noise test2018In: Hearing Research, ISSN 0378-5955, E-ISSN 1878-5891, Vol. 369, p. 67-78Article in journal (Refereed)
    Abstract [en]

    Difficulties arising in everyday speech communication often result from the acoustical environment, which may contain interfering background noise or competing speakers. Thus, listening and understanding speech in noise can be exhausting. Two experiments are presented in the current study that further explored the impact of masker type and Signal-to-Noise Ratio (SNR) on listening effort by means of pupillometry. In both studies, pupillary responses of participants were measured while performing the Danish Hearing in Noise Test (HINT; Nielsen and Dau, 2011). The first experiment aimed to replicate and extend earlier observed effects of noise type and semantic interference on listening effort (Koelewijn et al., 2012). The impact of three different masker types, i.e. a fluctuating noise, a 1-talker masker and a 4-talker masker on listening effort was examined at a fixed speech intelligibility. In a second experiment, effects of SNR on listening effort were examined while presenting the HINT sentences across a broad range of fixed SNRs corresponding to intelligibility scores ranging from 100% to 0% correct performance. A peak pupil dilation (PPD) was calculated and a Growth Curve Analysis (GCA) was performed to examine listening effort involved in speech recognition as a function of SNR. The results of two experiments showed that the pupil dilation response is highly affected by both masker type and SNR when performing the HINT. The PPD was highest, suggesting the highest level of effort, for speech recognition in the presence of the 1-talker masker in comparison to the 4-talker babble and the fluctuating noise masker. However, the disrupting effect of one competing talker disappeared for intelligibly levels around 50%. Furthermore, it was demonstrated that the pupillary response strongly varied as a function of SNRs. Listening effort was highest for intermediate SNRs with performance accuracies ranging between 30% and 70% correct. GCA revealed time-dependent effects of the SNR on the pupillary response that were not reflected in the PPD. (C) 2018 Elsevier B.V. All rights reserved.

  • 49.
    Werner, Mimmi
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Van De Water, Thomas R.
    Andersson, Therese
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Arnoldsson, Göran
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    Berggren, Diana
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Morphological and morphometric characteristics of vestibular hair cells and support cells in long term cultures of rat utricle explants2012In: Hearing Research, ISSN 0378-5955, E-ISSN 1878-5891, Vol. 283, no 1-2, p. 107-116Article in journal (Refereed)
    Abstract [en]

    A method for long term culture of utricular macula explants is demonstrated to be stable and reproducible over a period of 28 days in vitro (DIV). This culture system for four-day-old rat utricular maculae is potentially suitable for studies of hair cell loss, repair and regeneration processes as they occur in post-natal mammalian inner ear sensory epithelia. The cellular events that occur within utricular macula hair cell epithelia during 28 days of culture are documented from serial sections. Vestibular hair cells (HCs) and supporting cells (SCs) were systematically counted using light microscopy (LM) and the assistance of morphometric computer software. Ultrastructural observations were made with transmission electron microscopy (TEM) for describing the changes in the fine detailed morphological characteristics that occurred in the explants related to time in vitro. After 2 DIV the density of HCs was 77%, at 21 DIV it was 69%, and at 28 DIV it was 52% of HCs present at explantation. Between 2 DIV and 28 DIV there was a 1.7% decrease of the vestibular macula HC density per DIV. The corresponding decrease of SC density within the utricular explants was less than 1% per DIV. The overall morphology of the epithelia, i.e. relationship of HCs to SCs, was well preserved during the first two weeks in culture. After this time a slight deterioration of the epithelia was observed and although type I and type II HCs were identified by TEM observations, these two HC types could no longer be distinguished from one another by LM observations. In preparations cultured for 21 DIV, SC nuclei were located more apical and further away from the basal membrane compared to their position in macula explants fixed immediately after dissection. The loss of cells that occurred was probably due to expulsion from the apical (i.e. luminal) surface of the sensory epithelia, but no lesions of the apical lining or ruptures of the basal membrane were observed. There were no significant changes in the volume of the vestibular HC comprising macular epithelium during the observation period of 28 DIV.

  • 50.
    Werner, Mimmi
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Van De Water, Thomas R.
    Hammarsten, Peter
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Arnoldsson, Göran
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    Berggren, Diana
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Morphological and morphometric characterization of direct transdifferentiation of support cells into hair cells in ototoxin-exposed neonatal utricular explants2015In: Hearing Research, ISSN 0378-5955, E-ISSN 1878-5891, Vol. 321, p. 1-11Article in journal (Refereed)
    Abstract [en]

    We have studied aminoglycoside-induced vestibular hair-cell renewal using long-term culture of utricular macula explants from 4-day-old rats. Explanted utricles were exposed to 1 mM of gentamicin for 48 h, during 2nd and 3rd days in vitro (DIV), and then recovering in unsupplemented medium. Utricles were harvested at specified time points from the 2nd through the 28th DIV. The cellular events that occurred within hair cell epithelia during the culture period were documented from serial sectioned specimens. Vestibular hair cells (HCs) and supporting cells (SCs) were systematically counted using light microscopy (LM) with the assistance of morphometric software. Ultrastructural observations were made from selected specimens with transmission electron microscopy (TEM). After 7 DIV, i.e. four days after gentamicin exposure, the density of HCs was 11% of the number of HCs observed in non-gentamicin-exposed control explants. At 28 DIV the HC density was 61% of the number of HCs observed in the control group explant specimens. Simultaneously with this increase in HCs there was a corresponding decline in the number of SCs within the epithelium. The proportion of HCs in relation to SCs increased significantly in the gentamicin-exposed explant group during the 5th to the 28th DIV period of culture. There were no significant differences in the volume estimations of the gentamicin-exposed and the control group explants during the observed period of culture. Morphological observations showed that gentamicin exposure induced extensive loss of HCs within the epithelial layer, which retained their intact apical and basal linings. At 7 to 14 DIV (i.e. 3-11 days after gentamicin exposure) a pseudostratified epithelium with multiple layers of disorganized cells was observed. At 21 DIV new HCs were observed that also possessed features resembling SCs. After 28 DIV a new luminal layer of HCs with several layers of SCs located more basally characterized the gentamicin-exposed epithelium. No mitoses were observed within the epithelial layer of any explants. Our conclusion is that direct transdifferentiation of SCs into HCs was the only process contributing to the renewal of HCs after gentamicin exposure in these explants of vestibular inner ear epithelia obtained from the labyrinths of 4-day-old rats.

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