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  • 1.
    Aabel, Peder
    et al.
    Oslo Univ Hosp, Dept Med Biochem, Oslo, Norway;Akershus Univ Hosp, Ear Nose & Throat Dept, Div Surg, Lorenskog, Norway;Univ Oslo, Inst Clin Med, Div Surg, Oslo, Norway.
    Utheim, Tor Paaske
    Oslo Univ Hosp, Dept Med Biochem, Oslo, Norway;Univ Oslo, Inst Oral Biol, Fac Dent, Oslo, Norway.
    Olstad, Ole Kristoffer
    Oslo Univ Hosp, Dept Med Biochem, Oslo, Norway.
    Rask-Andersen, Helge
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Dilley, Rodney James
    Ear Sci Inst Australia, Perth, WA, Australia;Univ Western Australia, Ear Sci Ctr, Nedlands, WA, Australia;Univ Western Australia, Ctr Cell Therapy & Regenerat Med, Nedlands, WA, Australia.
    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, Ear Nose & Throat Dept, Div Surg, Lorenskog, Norway;Univ Oslo, Inst Clin Med, Div Surg, Oslo, Norway.
    Transcription and microRNA Profiling of Cultured Human Tympanic Membrane Epidermal Keratinocytes2018In: Journal of the Association for Research in Otolaryngology, ISSN 1525-3961, E-ISSN 1438-7573, Vol. 19, no 3, p. 243-260Article in journal (Refereed)
    Abstract [en]

    The human tympanic membrane (TM) has a thin outer epidermal layer which plays an important role in TM homeostasis and ear health. The specialised cells of the TM epidermis have a different physiology compared to normal skin epidermal keratinocytes, displaying a dynamic and constitutive migration that maintains a clear TM surface and assists in regeneration. Here, we characterise and compare molecular phenotypes in keratinocyte cultures from TM and normal skin. TM keratinocytes were isolated by enzymatic digestion and cultured in vitro. We compared global mRNA and microRNA expression of the cultured cells with that of human epidermal keratinocyte cultures. Genes with either relatively higher or lower expression were analysed further using the biostatistical tools g:Profiler and Ingenuity Pathway Analysis. Approximately 500 genes were found differentially expressed. Gene ontology enrichment and Ingenuity analyses identified cellular migration and closely related biological processes to be the most significant functions of the genes highly expressed in the TM keratinocytes. The genes of low expression showed a marked difference in homeobox (HOX) genes of clusters A and C, giving the TM keratinocytes a strikingly low HOX gene expression profile. An in vitro scratch wound assay showed a more individualised cell movement in cells from the tympanic membrane than normal epidermal keratinocytes. We identified 10 microRNAs with differential expression, several of which can also be linked to regulation of cell migration and expression of HOX genes. Our data provides clues to understanding the specific physiological properties of TM keratinocytes, including candidate genes for constitutive migration, and may thus help focus further research.

  • 2.
    Agrawal, Sumit
    et al.
    Western Univ, Dept Otolaryngol Head & Neck Surg, London, ON, Canada.
    Schart-Moren, Nadine
    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.
    Ladak, Hanif M.
    Western Univ, Dept Otolaryngol Head & Neck Surg, London, ON, Canada;Western Univ, Dept Med Biophys, London, ON, Canada;Western Univ, Dept Elect & Comp Engn, London, ON, Canada.
    Rask-Andersen, Helge
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Li, Hao
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    The secondary spiral lamina and its relevance in cochlear implant surgery2018In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 123, no 1, p. 9-18Article in journal (Refereed)
    Abstract [en]

    Objective: We used synchrotron radiation phase contrast imaging (SR-PCI) to study the 3D microanatomy of the basilar membrane (BM) and its attachment to the spiral ligament (SL) (with a conceivable secondary spiral lamina [SSL] or secondary spiral plate) at the round window membrane (RWM) in the human cochlea. The conception of this complex anatomy may be essential for accomplishing structural preservation at cochlear implant surgery.

    Material and methods: Sixteen freshly fixed human temporal bones were used to reproduce the BM, SL, primary and secondary osseous spiral laminae (OSL), and RWM using volume-rendering software. Confocal microscopy immunohistochemistry (IHC) was performed to analyze the molecular constituents.

    Results: SR-PCI reproduced the soft tissues including the RWM, Reissner's membrane (RM), and the BM attachment to the lateral wall (LW) in three dimensions. A variable SR-PCI contrast enhancement was recognized in the caudal part of the SL facing the scala tympani (ST). It seemed to represent a SSL allied to the basilar crest (BC). The SSL extended along the postero-superior margin of the round window (RW) and immunohistochemically expressed type II collagen.

    Conclusions: Unlike in several mammalian species, the human SSL is restricted to the most basal portion of the cochlea around the RW. It anchors the BM and may influence its hydro-mechanical properties. It could also help to shield the BM from the RW. The microanatomy should be considered at cochlear implant surgery.

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  • 3.
    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.

  • 4. Anderson, Malin
    et al.
    Johnston, T.A.
    Newman, P.D.
    Rask-Andersen, Helge
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Internalization of nanoparticles into spiral ganglion cells2009In: Journal of nanoneuroscience, ISSN 1939-0637, Vol. 1, no 1, p. 75-84Article in journal (Refereed)
    Abstract [en]

    The delivery of drugs or genes to the inner ear in a controlled and biocompatible manner could lead to new treatments for conditions such as Ménière's disease, tinnitus, schwannomas of the ear, and for improving hearing. The concept of multifunctional nanoparticles, which are targetable, biodegradable, and traceable, has led to new approaches to controlled drug release and localized delivery to specific cell populations. Tissue-specific delivery can be achieved by functionally "addressed" nanostructures loaded with a therapeutic molecule. In the present study, we investigated the incorporation, distribution, and toxicology of amphiphilic block copolymer nanoparticles (NPs) in spiral ganglion (SG) cell cultures. Adult human and guinea pig SG neurons and glia/Schwann dissociated cell cultures were expanded, grown for several weeks, and then studied live using time-lapse video microscopy and high-resolution light microscopy. The cells were further characterized using immunocytochemistry for the neural marker TuJ1 and the glia cell markers S-100 and GFAP, and their morphology was studied in more detail using scanning electron microscopy (SEM). These cell cultures were exposed to fluorescently (Dil)-loaded NPs for different time periods and at different concentrations, and the uptake was studied using fluorescence microscopy. The study demonstrates that Dil-loaded NPs can be internalized into guinea pig SG neurons as well as into human and guinea pig SG glia/Schwann cells without indication of toxicity or reduced viability. After 4 hours, almost 100% of both the neurons and the glia cells had incorporated the NPs into the cytoplasm. No uptake could be detected in the nucleus and no evidence of internalization could be seen in axons or in the growth cone area of the neuron. Especially in the glia cells, the NPs were detected in small vesicles surrounding the nucleus and occasionally in the periphery of the cytoplasm. This information could lead to the development of more specialized NPs, targeting only SG neurons or Schwann cells.

  • 5.
    Andersson, Gerhard
    et al.
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Ekvall, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Kinnefors, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Nyberg, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Rask-Andersen, Helge
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Evaluation of quality of life and symptoms after translabyrinthine acoustic neuroma surgery1997In: The American journal of otology, ISSN 0192-9763, Vol. 18, no 4, p. 421-426Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE:

    This study aimed to describe the consequences of acoustic neuroma surgery in terms of symptoms and quality of life.

    STUDY DESIGN:

    This study was a retrospective case review.

    SETTING:

    The surgery was conducted in Uppsala, Sweden.

    PATIENTS:

    A consecutive sample of acoustic neuroma patients operated on between 1988 and 1994.

    INTERVENTION:

    All patients had been operated on with the translabyrinthine technique.

    MAIN OUTCOME MEASURES:

    A questionnaire was constructed including questions about the surgery and symptoms. The House and Brackmann scale was used for grading facial function and the Brackmann and Bars scale was used for self-assessment of facial function.

    RESULTS:

    Follow-up data were collected by a postal questionnaire sent out and returned by 141 patients, which yielded a 90% response rate. Normal to moderately impaired facial function (House I-III) was evident in 85.2% of patients, although residual facial problems were reported. Most considered hearing to be worse after surgery (80%), and tinnitus was found in 60% of the sample. Balance problems (45%), dizziness (19%), and headache/pain (22%) were also reported. Work ability was affected in 23%, and 37% reported a continued need for medical consultations, mainly because of facial problems and pain. Most (89%) were pleased with the preoperative information.

    CONCLUSIONS:

    This study showed that few patients with acoustic neuroma had experienced negative social consequences after surgery. Although not linked to the operation, residual symptoms were reported that may necessitate further rehabilitation.

  • 6.
    Andersson, Gerhard
    et al.
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Kinnefors, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Ekvall, Lars
    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.
    Tinnitus and translabyrinthine acoustic neuroma surgery1997In: Audiology & neuro-otology, ISSN 1420-3030, E-ISSN 1421-9700, Vol. 2, no 6, p. 403-409Article in journal (Refereed)
    Abstract [en]

    The purpose of this investigation was to study the effects of translabyrinthine acoustic neuroma surgery on tinnitus in a consecutive sample of patients operated on between 1988 and 1994 in Uppsala (Sweden). A postal questionnaire was returned by 141 patients, yielding a 90% response rate without reminder. The results showed that tinnitus was experienced by 70% of the patients before surgery and 60% after surgery. In general, low degrees of tinnitus distress were found, which was confirmed by the questionnaire results. Ratings of tinnitus distress after surgery, using the Klockhoff and Lindblom grading system, showed that 48% had tinnitus of grade I, 46% of grade II, and 6% of grade III. Pre- and postsurgery grading of distress did not change significantly. There was a 35% risk for developing tinnitus when no preoperative tinnitus was present and a 15% chance that tinnitus disappears when present preoperatively.

  • 7.
    Atturo, Francesca
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Barbara, Maurizio
    Rask-Andersen, Helge
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Is the Human Round Window Really Round?: An Anatomic Study With Surgical Implications2014In: Otology and Neurotology, ISSN 1531-7129, E-ISSN 1537-4505, Vol. 35, no 8, p. 1354-1360Article in journal (Refereed)
    Abstract [en]

    Hypothesis: Human round window (RW) presents anatomic variations that may influence surgical approach. Background: The true shape of the human RW has been divisive since its first description in 1772 by Antonio Scarpa. Introduction of novel surgical strategies in recent years have raised its significance. Here, the human RW size and shape variations were documented in microdissected human temporal bones. Methods: An archival collection of human microdissected temporal bones was analyzed. RW rim could be delineated and photographed from the labyrinthine aspect and its topography assessed. Results: Human RW is seldom round but ovoid or orthogonal, skewed, and nonplanar (saddlelike). Membrane is fan shaped or conical with an anteroinferior and a posterosuperior part. The mean longest diameter was 1.90 mm, and the smallest one is 1.54 mm. The mean diameter from the crista fenestra was 1.31 mm. The mean area of the RW was 2.08 mm(2), which varied between 0.99 and 3.20 mm(2). The crista fenestrae of the anterior component form a "doorstep" that may limit the entry to the scala tympani from the RW niche. Conclusion: The alternate anatomic features of the human RW may influence its surgical access and designs of implants aimed at targeting this region.

  • 8.
    Atturo, Francesca
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Barbara, Maurizio
    Rask-Andersen, Helge
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    On the Anatomy of the 'Hook' Region of the Human Cochlea and How It Relates to Cochlear Implantation2014In: Audiology & neuro-otology, ISSN 1420-3030, E-ISSN 1421-9700, Vol. 19, no 6, p. 378-385Article in journal (Refereed)
    Abstract [en]

    Background: The optimal insertion route for an electrode array in hearing preservation cochlear implantation (CI) surgery is still tentative. Both cochleostomy (CO) and round window (RW) techniques are used today. In the present study we analyzed size variations and topographic anatomy of the 'hook' region of the human cochlea to better comprehend the Testo effects of various electric array insertion modes. Material and Methods: Size variations of the cochlear 'hook' region were assessed in 23 human, microdissected temporal bones by measuring the distances between the oval and round windows, also outlining the spiral ligament/spiral lamina. Influence of size variations on spiral ligament position and fundamentals for different surgical approaches were evaluated in a subset of 'small' and 'large' cochleae performing different types of CO. In addition, the relationship between the microdissected accessory canal housing the inferior cochlear vein and the RW was analyzed. Results: The lateral vestibular wall and the cochlear 'hook' displayed large anatomic variations that greatly influenced the size of the potential surgical area. Results showed that only very inferiorly located CO entered the scala tympani without causing trauma to the spiral ligament and spiral lamina. An inferior approach may challenge the inferior cochlear vein. Conclusion: Preoperative assessment of the distance between the round and oval windows may direct the surgeon before CI hearing- preservation surgery. CO techniques, especially in 'small' ears, may lead to frequent damage to the inner ear structures. In those cases with substantial residual hearing, CI surgery may be better performed through a RW approach.  

  • 9.
    Atturo, Francesca
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Schart-Moren, Nadine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Larsson, Sune
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Rask-Andersen, Helge
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery. Uppsala Univ Hosp, Otolaryngol Sect, Dept Surg Sci Head & Neck Surg, Uppsala, Sweden.
    Li, Hao
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    The Human Cochlear Aqueduct and Accessory Canals: a Micro-CT Analysis Using a 3D Reconstruction Paradigm2018In: Otology and Neurotology, ISSN 1531-7129, E-ISSN 1537-4505, Vol. 39, no 6, p. e429-e435Article in journal (Refereed)
    Abstract [en]

    Objective: We sought to study the anatomic variations of the cochlear aqueduct and its accessory canals in human temporal bones using micro-CT and a 3D reconstruction paradigm. More knowledge about the anatomic variations of these structures, particularly at the basal turn of the cochlea and round window niche, may be important to better preserve residual hearing as well as the neural supply during cochlear implant surgery.

    Methods: An archival collection of 30 human temporal bones underwent micro-CT and 3D reconstruction. A surface enhancement paradigm was applied. The application displays reconstructed slices as a 3D object with realistic 3D visualization of scanned objects. Virtual sectioning or cropping of the petrous bone presented subsequent areas. Thereby, the bony canals could be followed from inside the basal turn of cochlea and middle ear to the jugular foramen.

    Results: The cochlear aqueduct was always paralleled by an accessory canal containing the inferior cochlear vein. It ran from the basal turn of the cochlea and exited laterally in the jugular foramen. In 70% of the cases, a secondary accessory canal was observed and it derived mostly from a depression or infundibulum located in the floor of the round window niche. This canal also exited in the jugular foramen. The secondary accessory canal occasionally anastomosed with the primary accessory canal suggesting that it contains a vein that drains middle ear blood to the cranial sinus.

    Conclusion: Micro-CT with 3D surface reconstruction paradigm offers new possibilities to study the topographic anatomy of minor details in the human inner ear. The technique creates simulated transparent castings of the labyrinth with a coinciding surface view through enhancement of contrast between boundaries. Accessory canals that drain blood from the cochlea, spiral ganglion, and middle ear could be characterized three-dimensionally.

  • 10. Bagger-Sjöbäck, Dan
    et al.
    Rask-Andersen, Helge
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Pathology of the vestibular organ2008In: Scott-Brown textbook of otolaryngology / [ed] Michael Gleeson, London: Hodder Arnold , 2008, 7, p. 3147-3157Chapter in book (Other (popular science, discussion, etc.))
  • 11.
    Boström, Marja
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Anderson, Malin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Lindholm, Dan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Park, Kyoung-Ho
    Schrott-Fischer, Annelies
    Pfaller, Kristian
    Glueckert, Rudolf
    Rask-Andersen, Helge
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Neural network and "Ganglion" formations in vitro: a video microscopy and scanning electron microscopy study on adult cultured spiral ganglion cells.2007In: Otology and Neurotology, ISSN 1531-7129, E-ISSN 1537-4505, Vol. 28, no 8, p. 1109-1119Article in journal (Refereed)
    Abstract [en]

    Hypothesis: To analyze if adult-dissociated spiral ganglion cells may be propagated in vitro for later use in transplantation models to form integrated neural networks. Background: Hearing loss is often associated with primary or secondary spiral ganglion cell degeneration. New strategies for cell repair and tissue engineering warrants further elucidation of the regenerative capacity of the auditory nerve. Methods: We used in vitro/in video microscopy in combination with immunocytochemistry and field emission scanning electron microscopy to analyze neural development and network formation from dissociated adult guinea pig spiral ganglion cells. Cells were cultured in serum-free medium and in the presence of brain-derived neurotrophic factor, neurotrophin 3, and glia cell line-derived neurotrophic factor for up to 8 weeks. Results: Time-lapse video microscopy and scanning electron microscopy exposed the propagation of auditory neurons and the role of neural growth cones in axon locomotion, fasciculation, and nuclear migration, often ensuing in cell congregation (ganglion-like formations) during network formation. Axons were sometimes ensheathed by adjoining S-100/glia fibrillary acidic protein-expressing cells. A few expanding neurons were nestin positive and sometimes incorporated the markers of proliferating cells Ki67 and 5'-bromo-2-deoxyuridine. Neurons expressed the markers and transcription factors for neural development neurogenin 1, neurogenic differentiation factor 1, Brn3a, and GATA binding protein 3, as well as the neural markers beta-III tubulin, NeuN, and neurofilament 160 during this process. Conclusion: This method of culturing and expanding spiral ganglion neurons in vitro may be useful in further studies of cell transplantation models aiming to restore the injured inner ear.

  • 12.
    Boström, Marja
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Plastic Surgery.
    Khalifa, Shaden
    Boström, Henrik
    Liu, Wei
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Friberg, Ulla
    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.
    Effects of Neurotrophic Factors on Growth and Glial Cell Alignment of Cultured Adult Spiral Ganglion Cells2009In: Audiology & neuro-otology, ISSN 1420-3030, E-ISSN 1421-9700, Vol. 15, no 3, p. 175-186Article in journal (Refereed)
    Abstract [en]

    Adult spiral ganglion cells were cultured in chorus to assess the influence of the neurotrophins brain-derived neurotrophic factor, neurotrophin 3 and glial cell line-derived neurotrophic factor (GDNF) on neurite growth and Schwann cell alignment. Over 1500 measurements were collected using each factor at 10 ng/ml and all three in combination. Evaluation was made with GDNF at concentrations of up to 100 ng/ml. Neurite dimensions were assessed at days 5, 7, 9 and 11 using a computer-based program (Axon Analyzer). GDNF had a strong effect on spiral ganglion cell growth almost attaining the level of all three factors in combination. GDNF increased glial cell alignment and nerve bundle formation. Results show the potential of GDNF to maintain and possibly restore auditory nerve integrity.

  • 13.
    Cai, Yixiao
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Edin, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Jin, Zhe
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiology.
    Alexsson, Andrei
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Gudjonsson, Olafur
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Liu, Wei
    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.
    Karlsson, Mikael
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Li, Hao
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Strategy towards independent electrical stimulation from cochlear implants: Guided auditory neuron growth on topographically modified nanocrystalline diamond2016In: Acta Biomaterialia, ISSN 1742-7061, E-ISSN 1878-7568, Vol. 31, p. 211-220Article in journal (Refereed)
    Abstract [en]

    Cochlear implants (CI) have been used for several decades to treat patients with profound hearing loss. Nevertheless, results vary between individuals, and fine hearing is generally poor due to the lack of discrete neural stimulation from the individual receptor hair cells. A major problem is the deliverance of independent stimulation signals to individual auditory neurons. Fine hearing requires significantly more stimulation contacts with intimate neuron/electrode interphases from ordered axonal re-growth, something current CI technology cannot provide.

    Here, we demonstrate the potential application of micro-textured nanocrystalline diamond (NCD) surfaces on CI electrode arrays. Such textured NCD surfaces consist of micrometer-sized nail-head-shaped pillars (size 5 5 lm2) made with sequences of micro/nano-fabrication processes, including sputtering, photolithography and plasma etching.

    The results show that human and murine inner-ear ganglion neurites and, potentially, neural progenitor cells can attach to patterned NCD surfaces without an extracellular matrix coating. Microscopic methods revealed adhesion and neural growth, specifically along the nail-head-shaped NCD pillars in an ordered manner, rather than in non-textured areas. This pattern was established when the inter-NCD pillar distance varied between 4 and 9 lm.

    The findings demonstrate that regenerating auditory neurons show a strong affinity to the NCD pillars, and the technique could be used for neural guidance and the creation of new neural networks. Together with the NCD’s unique anti-bacterial and electrical properties, patterned NCD surfaces could provide designed neural/electrode interfaces to create independent electrical stimulation signals in CI electrode arrays for the neural population.

  • 14.
    Chacko, L. Johnson
    et al.
    Med Univ Innsbruck, Dept Otorhinolaryngol, Anichstr 35, A-6020 Innsbruck, Austria..
    Blumer, M. J. F.
    Med Univ Innsbruck, Dept Anat Histol & Embryol, Div Clin & Funct Anat, Muellerstr 59, A-6020 Innsbruck, Austria..
    Pechriggl, E.
    Med Univ Innsbruck, Dept Anat Histol & Embryol, Div Clin & Funct Anat, Muellerstr 59, A-6020 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.
    Dietl, W.
    Med Univ Innsbruck, Dept Otorhinolaryngol, Anichstr 35, A-6020 Innsbruck, Austria..
    Haim, A.
    Med Univ Innsbruck, Dept Plast Reconstruct & Aesthet Surg, Innerkoflerstr 1, A-6020 Innsbruck, Austria..
    Fritsch, H.
    Med Univ Innsbruck, Dept Anat Histol & Embryol, Div Clin & Funct Anat, Muellerstr 59, A-6020 Innsbruck, Austria..
    Glueckert, R.
    Med Univ Innsbruck, Dept Otorhinolaryngol, Anichstr 35, A-6020 Innsbruck, Austria.;Tirol Kliniken, Univ Clin Innsbruck, Anichstr 35, A-6020 Innsbruck, Austria..
    Dudas, J.
    Med Univ Innsbruck, Dept Otorhinolaryngol, Anichstr 35, A-6020 Innsbruck, Austria..
    Schrott-Fischer, A.
    Med Univ Innsbruck, Dept Otorhinolaryngol, Anichstr 35, A-6020 Innsbruck, Austria..
    Role of BDNF and neurotrophic receptors in human inner ear development2017In: Cell and Tissue Research, ISSN 0302-766X, E-ISSN 1432-0878, Vol. 370, no 3, p. 347-363Article in journal (Refereed)
    Abstract [en]

    The expression patterns of the neurotrophin, brain-derived neurotrophic factor, BDNF, and the neurotrophic receptors-p75NTR and Trk receptors-in the developing human fetal inner ear between the gestational weeks (GW) 9 to 12 are examined via in situ hybridization and immunohistochemistry. BDNF mRNA expression was highest in the cochlea at GW 9 but declined in the course of development. In contrast to embryonic murine specimens, a decline in BDNF expression from the apical to the basal turn of the cochlea could not be observed. p75NTR immunostaining was most prominent in the nerve fibers that penetrate into the sensory epithelia of the cochlea, the urticule and the saccule as gestational age progresses. TrkB and TrkC expression intensified towards GW 12, at which point the BDNF mRNA localization was at its lowest. TrkA expression was limited to fiber subpopulations of the facial nerve at GW 10. In the adult human inner ear, we observed BDNF mRNA expression in the apical poles of the cochlear hair cells and supporting cells, while in the adult human utricle, the expression was localized in the vestibular hair cells. We demonstrate the highly specific staining patterns of BDNF mRNA and its putative receptors over a developmental period in which multiple hearing disorders are manifested. Our findings suggest that BDNF and neurotrophin receptors are important players during early human inner ear development. In particular, they seem to be important for the survival of the afferent sensory neurons.

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  • 15.
    Chacko, Lejo Johnson
    et al.
    Med Univ Innsbruck, Dept Otorhinolaryngol, Anichstr 35, A-6020 Innsbruck, Austria.
    Sergi, Consolato
    Univ Alberta, Dept Lab Med & Pathol, 8440 112 St NW, Edmonton, AB T6G 2B7, Canada;Univ Alberta, Dept Pediat, 8440 112 St NW, Edmonton, AB T6G 2B7, Canada.
    Eberharter, Theresa
    Med Univ Innsbruck, Dept Otorhinolaryngol, Anichstr 35, A-6020 Innsbruck, Austria.
    Dudas, Jozsef
    Med Univ Innsbruck, Dept Otorhinolaryngol, Anichstr 35, A-6020 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. Uppsala Univ Hosp, Uppsala, Sweden.
    Hoermann, Romed
    Med Univ Innsbruck, Dept Anat Histol & Embryol, Div Clin & Funct Anat, Muellerstr 59, A-6020 Innsbruck, Austria.
    Fritsch, Helga
    Med Univ Innsbruck, Dept Anat Histol & Embryol, Div Clin & Funct Anat, Muellerstr 59, A-6020 Innsbruck, Austria.
    Fischer, Natalie
    Tirol Kliniken, Univ Clin Innsbruck, Anichstr 35, A-6020 Innsbruck, Austria.
    Glueckert, Rudolf
    Med Univ Innsbruck, Dept Otorhinolaryngol, Anichstr 35, A-6020 Innsbruck, Austria;Tirol Kliniken, Univ Clin Innsbruck, Anichstr 35, A-6020 Innsbruck, Austria.
    Schrott-Fischer, Anneliese
    Med Univ Innsbruck, Dept Otorhinolaryngol, Anichstr 35, A-6020 Innsbruck, Austria.
    Early appearance of key transcription factors influence the spatiotemporal development of the human inner ear2020In: Cell and Tissue Research, ISSN 0302-766X, E-ISSN 1432-0878, Vol. 379, no 3, p. 459-471Article in journal (Refereed)
    Abstract [en]

    Expression patterns of transcription factors leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5), transforming growth factor-beta-activated kinase-1 (TAK1), SRY (sex-determining region Y)-box 2 (SOX2), and GATA binding protein 3 (GATA3) in the developing human fetal inner ear were studied between the gestation weeks 9 and 12. Further development of cochlear apex between gestational weeks 11 and 16 (GW11 and GW16) was examined using transmission electron microscopy. LGR5 was evident in the apical poles of the sensory epithelium of the cochlear duct and the vestibular end organs at GW11. Immunostaining was limited to hair cells of the organ of Corti by GW12. TAK1 was immune positive in inner hair cells of the organ of Corti by GW12 and colocalized with p75 neurotrophic receptor expression. Expression for SOX2 was confined primarily to the supporting cells of utricle at the earliest stage examined at GW9. Intense expression for GATA3 was presented in the cochlear sensory epithelium and spiral ganglia at GW9. Expression of GATA3 was present along the midline of both the utricle and saccule in the zone corresponding to the striolar reversal zone where the hair cell phenotype switches from type I to type II. The spatiotemporal gradient of the development of the organ of Corti was also evident with the apex of the cochlea forming by GW16. It seems that highly specific staining patterns of several transcriptions factors are critical in guiding the genesis of the inner ear over development. Our findings suggest that the spatiotemporal gradient in cochlear development extends at least until gestational week 16.

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  • 16. Couloigner, Vincent
    et al.
    Teixeira, Marie
    Sterkers, Olivier
    Rask-Andersen, Helge
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Ferrary, Evelyne
    [The endolymphatic sac: its roles in the inner ear]2004In: Med Sci (Paris), ISSN 0767-0974, Vol. 20, no 3, p. 304-10Article in journal (Other scientific)
  • 17.
    Danckwardt-Lillieström, Niklas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Friberg, Ulla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck 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.
    "Endolymphatic sacitis" in a case of active Menière's disease: an ultrastructural histopathologic investigation1997In: Annals of Otology, Rhinology and Laryngology, ISSN 0003-4894, E-ISSN 1943-572X, Vol. 106, no 3, p. 190-198Article in journal (Refereed)
    Abstract [en]

    An ultrastructural analysis of an entire intraosseous endolymphatic sac (ES) from a patient with active, well-documented Menière's disease was performed for the first time. The results were compared with those obtained from ES biopsy material from patients with acoustic neuromas. The ES was small in size and showed signs of focal inflammation with intraepithelial invasion by mononuclear cells. At these places the normal fine structure, including the vascular anatomy, was altered. The possible relationship between these changes and Meniere's disease is discussed.

  • 18.
    Danckwardt-Lillieström, Niklas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Friberg, Ulla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck 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.
    Steriocilia-like structures in the endolymphatic sac in Ménière's disease and acoustic neuroma1998In: Journal for Oto-Rhino-Laryngology, ISSN 0301-1569, E-ISSN 1423-0275, Vol. 60, no 4, p. 190-197Article in journal (Refereed)
    Abstract [en]

    The vestibular aqueduct was surgically removed in 3 patients undergoing labyrinthectomy due to severe Ménière's disease (MD). Stereocilia-like structures were found in the luminal contents of the endolymphatic sac (ES) in all of these patients. The ES from 18 patients with acoustic neuroma were used as controls. In 1 of these, numerous stereocilia-like structures were found in the ES and in 3 additional patients, a few isolated cilia-like structures were disclosed. The findings may suggest an ongoing hair cell degeneration in the inner ear that is more advanced in patients with MD. The data also suggest that the endolymphatic duct is patent and that a longitudinal flow of endolymph also occurs in patients with MD.

  • 19.
    Danckwardt-Lillieström, Niklas
    et al.
    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.
    Friberg, Ulla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Kinnefors, Anders