| 1. |
- Li, Hao, et al.
(författare)
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Regeneration in the Auditory Organ in Cuban and African Dwarf Crocodiles (Crocodylus rhombifer and Osteolaemus tetraspis) Can We Learn From the Crocodile How to Restore Our Hearing?
- 2022
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Ingår i: Frontiers in Cell and Developmental Biology. - : Frontiers Media S.A.. - 2296-634X. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Background: In several non-mammalian species, auditory receptors undergo cell renewal after damage. This has raised hope of finding new options to treat human sensorineural deafness. Uncertainty remains as to the triggering mechanisms and whether hair cells are regenerated even under normal conditions. In the present investigation, we explored the auditory organ in the crocodile to validate possible ongoing natural hair cell regeneration. Materials and Methods: Two male Cuban crocodiles (Crocodylus rhombifer) and an adult male African Dwarf crocodile (Osteolaemus tetraspis) were analyzed using transmission electron microscopy and immunohistochemistry using confocal microscopy. The crocodile ears were fixed in formaldehyde and glutaraldehyde and underwent micro-computed tomography (micro-CT) and 3D reconstruction. The temporal bones were drilled out and decalcified. Results: The crocodile papilla basilaris contained tall (inner) and short (outer) hair cells surrounded by a mosaic of tightly connected supporting cells coupled with gap junctions. Afferent neurons with and without ribbon synapses innervated both hair cell types. Supporting cells occasionally showed signs of trans-differentiation into hair cells. They expressed the MAFA and SOX2 transcription factors. Supporting cells contained organelles that may transfer genetic information between cells, including the efferent nerve fibers during the regeneration process. The tectorial membrane showed signs of being replenished and its architecture being sculpted by extracellular exosome-like proteolysis. Discussion: Crocodilians seem to produce new hair cells during their life span from a range of supporting cells. Imposing efferent nerve fibers may play a role in regeneration and re-innervation of the auditory receptors, possibly triggered by apoptotic signals from wasted hair cells. Intercellular signaling may be accomplished by elaborate gap junction and organelle systems, including neural emperipolesis. Crocodilians seem to restore and sculpt their tectorial membranes throughout their lives.
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| 2. |
- Liu, Wei, et al.
(författare)
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A combined genome-wide association and molecular study of age-related hearing loss in H. sapiens
- 2021
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Ingår i: BMC Medicine. - : BioMed Central (BMC). - 1741-7015. ; 19:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Sensorineural hearing loss is one of the most common sensory deficiencies. However, the molecular contribution to age-related hearing loss is not fully elucidated.METHODS: We performed genome-wide association studies (GWAS) for hearing loss-related traits in the UK Biobank (N = 362,396) and selected a high confidence set of ten hearing-associated gene products for staining in human cochlear samples: EYA4, LMX1A, PTK2/FAK, UBE3B, MMP2, SYNJ2, GRM5, TRIOBP, LMO-7, and NOX4.RESULTS: All proteins were found to be expressed in human cochlear structures. Our findings illustrate cochlear structures that mediate mechano-electric transduction of auditory stimuli, neuronal conductance, and neuronal plasticity to be involved in age-related hearing loss.CONCLUSIONS: Our results suggest common genetic variation to influence structural resilience to damage as well as cochlear recovery after trauma, which protect against accumulated damage to cochlear structures and the development of hearing loss over time.
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| 3. |
- Aabel, Peder, et al.
(författare)
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Transcription and microRNA Profiling of Cultured Human Tympanic Membrane Epidermal Keratinocytes
- 2018
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Ingår i: Journal of the Association for Research in Otolaryngology. - : SPRINGER. - 1525-3961 .- 1438-7573. ; 19:3, s. 243-260
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 4. |
- Agrawal, Sumit, et al.
(författare)
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The secondary spiral lamina and its relevance in cochlear implant surgery
- 2018
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Ingår i: Upsala Journal of Medical Sciences. - : TAYLOR & FRANCIS LTD. - 0300-9734 .- 2000-1967. ; 123:1, s. 9-18
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Tidskriftsartikel (refereegranskat)abstract
- 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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| 5. |
- Anderson, Malin, et al.
(författare)
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Internalization of nanoparticles into spiral ganglion cells
- 2009
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Ingår i: Journal of nanoneuroscience. - : American Scientific Publishers. - 1939-0637 .- 1939-0653. ; 1:1, s. 75-84
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 6. |
- Anderson, Malin, et al.
(författare)
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Structure and locomotion of adult in vitro regenerated spiral ganglion growth cones : a study using video microscopy and SEM
- 2006
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Ingår i: Hearing Research. - : Elsevier BV. - 0378-5955 .- 1878-5891. ; 215:1-2, s. 97-107
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 7. |
- Andersson, Gerhard, et al.
(författare)
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Evaluation of quality of life and symptoms after translabyrinthine acoustic neuroma surgery
- 1997
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Ingår i: The American journal of otology. - 0192-9763. ; 18:4, s. 421-426
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 8. |
- Andersson, Gerhard, et al.
(författare)
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Tinnitus and translabyrinthine acoustic neuroma surgery
- 1997
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Ingår i: Audiology & neuro-otology. - : S. Karger AG. - 1420-3030 .- 1421-9700. ; 2:6, s. 403-409
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 9. |
- Atturo, Francesca, et al.
(författare)
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Is the Human Round Window Really Round? : An Anatomic Study With Surgical Implications
- 2014
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Ingår i: Otology and Neurotology. - 1531-7129 .- 1537-4505. ; 35:8, s. 1354-1360
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 10. |
- Atturo, Francesca, et al.
(författare)
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On the Anatomy of the 'Hook' Region of the Human Cochlea and How It Relates to Cochlear Implantation
- 2014
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Ingår i: Audiology & neuro-otology. - : S. Karger AG. - 1420-3030 .- 1421-9700. ; 19:6, s. 378-385
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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