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The Human Vestibular Aqueduct, Endolymphatic Duct and Sac: A Morphological Study Using Micro-CT, Super Resolution Immunohistochemistry and Synchrotron Phase Contrast Imaging
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.ORCID-id: 0000-0001-5825-9160
2020 (engelsk)Doktoravhandling, med artikler (Annet vitenskapelig)
Abstract [en]

The inner ear lies sheltered in the temporal bone and consists of basically three parts: the cochlea (the hearing organ), the vestibular (the balance organ), and the endolymphatic duct (ED) and endolymphatic sac (ES). The ES and ED are located in a bony canal, the vestibular aqueduct (VA), located on the medial side of the vestibule. While the functions of the cochlea and the vestibular part of the inner ear are rather well studied, our knowledge of the function/s of the ES and ED remains limited and has intrigued scientists for centuries. Earlier studies have supported several theories, such as being an immune mediator, an aid in pressure regulation, related to the absorption of endolymph, and the production of endolymph.

 Otologic disorders, which affect both hearing and balance, such as Meniere’s disease (MD) and large vestibular aqueduct syndrome (LVAS), have been linked to dysfunction of the ES/ED. Studies of the human inner ear are fairly sparse. Research on the ES and ED have mainly been performed on animals, although both the anatomy and function may differ among various species.

This thesis aims to further investigate the anatomy and function of the human ES and ED with the two otologic disorders MD and LVAS in mind. To achieve this, we have used novel imaging techniques, such as super-resolution structured illumination microscopy (SR-SIM), micro-computerized tomography (micro-CT), and synchrotron radiation phase-contrast imaging (SR-PCI). The material used for imaging comes from different sources: human archival temporal bones from the Uppsala temporal bone collection; human fresh-frozen cadaveric bones from our collaborators at Western University, in London, Ontario, Canada; and fresh-frozen human ES harvested during vestibular schwannoma surgery after securing ethical permission.

The results of these studies describe the micro-anatomy of the VA, ED and ES down to a nanoscopic level. The discussion is based on the findings, relating them to earlier research with clinical implications regarding MD and LVAS.

sted, utgiver, år, opplag, sider
Uppsala: Acta Universitatis Upsaliensis, 2020. , s. 71
Serie
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1647
Emneord [en]
Endolymphatic sac, endolymphatic duct, vestibular aqueduct, Meniere's disease, LVAS, micro-CT, synchrotron phase contrast imaging
HSV kategori
Forskningsprogram
Medicinsk vetenskap
Identifikatorer
URN: urn:nbn:se:uu:diva-406848ISBN: 978-91-513-0901-9 (tryckt)OAI: oai:DiVA.org:uu-406848DiVA, id: diva2:1414579
Disputas
2020-05-07, Enghoffsalen, Akademiska sjukhuset, Ing 50, Uppsala, 09:00 (svensk)
Opponent
Veileder
Tilgjengelig fra: 2020-04-16 Laget: 2020-03-13 Sist oppdatert: 2020-05-19
Delarbeid
1. The Human Vestibular Aqueduct: Anatomical Characteristics and Enlargement Criteria
Åpne denne publikasjonen i ny fane eller vindu >>The Human Vestibular Aqueduct: Anatomical Characteristics and Enlargement Criteria
2016 (engelsk)Inngår i: Otology and Neurotology, ISSN 1531-7129, E-ISSN 1537-4505, Vol. 37, nr 10, s. 1637-1645Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Hypothesis: The human vestibular aqueduct (VA) shows great anatomical variations, and imaging can be difficult, so we need more data on the normal anatomy of the VA for better radiologic evaluation of large vestibular aqueduct syndrome (LVAS). Background: The normal anatomy of the human VA was analyzed in micro-dissected human temporal bones. Methods: The study is based on two sets of human temporal bones. One set of 32 human temporal bones was selected from a collection of 50 micro-dissected specimens. The outline of the intraosseous portion of the VA was drawn and digitized, and dimensions were assessed. The other set of 20 plastic molds were randomly selected from a collection of 324 specimens, and the VA dimensions were assessed. Results: Measurements from this study are presented in means, standard deviations, and ranges. The results from these measurements are considered normal and compared with previously published data. The variations in the normal anatomy of the VA are presented and discussed. Conclusion: The VA courses sagittal in the human skull. Therefore, we recommend the lateral projection (reformatted) to demonstrate the VA in LVAS patients. We advocate assessing: 1) the width (or height) of the external aperture (EA), 2) the width at the half distance between the EA and the common crus (CC), and if possible 3) the width of the proximal portion of the VA. Based on the measurements, our criteria for enlargement are 2.0mm or greater, 1.5mm or greater, and more than 1mm at these sites.

Emneord
LVAS, Pendrin, SLC26A4, Vestibular aqueduct
HSV kategori
Identifikatorer
urn:nbn:se:uu:diva-311179 (URN)10.1097/MAO.0000000000001203 (DOI)000388185000036 ()27631836 (PubMedID)
Tilgjengelig fra: 2016-12-22 Laget: 2016-12-22 Sist oppdatert: 2020-03-13bibliografisk kontrollert
2. The Human Endolymphatic Sac and Inner Ear Immunity: Macrophage Interaction and Molecular Expression
Åpne denne publikasjonen i ny fane eller vindu >>The Human Endolymphatic Sac and Inner Ear Immunity: Macrophage Interaction and Molecular Expression
Vise andre…
2019 (engelsk)Inngår i: Frontiers in Immunology, E-ISSN 1664-3224, Vol. 9, artikkel-id 3181Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Background: The endolymphatic sac (ES) is endowed with a multitude of white blood cells that may trap and process antigens that reach the inner ear from nearby infection-prone areas, it thus serves as an immunologic defense organ. The human ES, and unexpectedly the rest of the inner ear, has been recently shown to contain numerous resident macrophages. In this paper, we describe ES macrophages using super-resolution structured fluorescence microscopy (SR-SIM) and speculate on these macrophages' roles in human inner ear defense.

Material and Methods: After ethical permission was obtained, human vestibular aqueducts were collected during trans-labyrinthine surgery for acoustic neuroma removal. Tissues were placed in fixative before being decalcified, rapidly frozen, and cryostat sectioned. Antibodies against IBA1, cytokine fractalkine (CX3CL1), toll-like receptor 4 (TLR4), cluster of differentiation (CD) 68, CD11b, CD4, CD8, and the major histocompatibility complex type II (MHCII) were used for immunohistochemistry.

Results: A large number of IBA1-positive cells with different morphologies were found to reside in the ES; the cells populated surrounding connective tissue and the epithelium. Macrophages interacted with other cells, showed migrant behavior, and expressed immune cell markers, all of which suggest their active role in the innate and adaptive inner ear defense and tolerance.

Discussion: High-resolution immunohistochemistry shows that antigens reaching the ear may be trapped and processed by an immune cell machinery located in the ES. Thereby inflammatory activity may be evaded near the vulnerable inner ear sensory structures. We speculate on the immune defensive link between the ES and the rest of the inner ear.

Emneord
human, cochlea, macrophages, IBA1, structured illumination microscopy
HSV kategori
Identifikatorer
urn:nbn:se:uu:diva-377333 (URN)10.3389/fimmu.2018.03181 (DOI)000457362000001 ()30774637 (PubMedID)
Tilgjengelig fra: 2019-02-25 Laget: 2019-02-25 Sist oppdatert: 2024-01-17bibliografisk kontrollert
3. A Micro-CT and Synchrotron Imaging Study of the Human Endolymphatic Duct with Special Reference to Endolymph Outflow and Meniere's Disease
Åpne denne publikasjonen i ny fane eller vindu >>A Micro-CT and Synchrotron Imaging Study of the Human Endolymphatic Duct with Special Reference to Endolymph Outflow and Meniere's Disease
Vise andre…
2020 (engelsk)Inngår i: Scientific Reports, E-ISSN 2045-2322, Vol. 10, nr 1, artikkel-id 8295Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Meniere’s disease remains enigmatic, and has no treatment with sufficient evidence. The characteristic histopathological finding is endolymphatic hydrops, suggesting either an overproduction or decreased reabsorption of endolymph in the human inner ear. This study presents the first analysis of the vascular plexus around the human endolymphatic duct using micro computed tomography and coherent synchrotron radiation with phase contrast imaging. Using a software program, data were processed by volume-rendering with scalar opacity mapping to create transparent three-dimensional reconstructions. A rich vascular plexus was discovered around the endolymphatic duct that drained into collecting channels, linked to the vestibular venous outflow system. This network is believed to make up the principal route for endolymph outflow, and its associated malfunction may result in endolymphatic hydrops and Meniere’s disease.

HSV kategori
Identifikatorer
urn:nbn:se:uu:diva-406752 (URN)10.1038/s41598-020-65110-0 (DOI)000540568100088 ()32427861 (PubMedID)
Forskningsfinansiär
Swedish Research Council, 2017-03801
Merknad

De tre sista författarna delar sistaförfattarskapet

Tilgjengelig fra: 2020-03-11 Laget: 2020-03-11 Sist oppdatert: 2022-09-15bibliografisk kontrollert
4. "Reversed polarization" of Na/K-ATPase — a sign of inverted transport in the human endolymphatic sac: a super-resolution structured illumination microscopy (SR-SIM) study
Åpne denne publikasjonen i ny fane eller vindu >>"Reversed polarization" of Na/K-ATPase — a sign of inverted transport in the human endolymphatic sac: a super-resolution structured illumination microscopy (SR-SIM) study
2020 (engelsk)Inngår i: Cell and Tissue Research, ISSN 0302-766X, E-ISSN 1432-0878, Vol. 379, nr 3, s. 445-457Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

The human endolymphatic sac (ES) is believed to regulate inner ear fluid homeostasis and to be associated with Meniere's disease (MD). We analyzed the ion transport protein sodium/potassium-ATPase (Na/K-ATPase) and its isoforms in the human ES using super-resolution structured illumination microscopy (SR-SIM). Human vestibular aqueducts were collected during trans-labyrinthine vestibular schwannoma surgery after obtaining ethical permission. Antibodies against various isoforms of Na/K-ATPase and additional solute-transporting proteins, believed to be essential for ion and fluid transport, were used for immunohistochemistry. A population of epithelial cells of the human ES strongly expressed Na/K-ATPase α1, β1, and β3 subunit isoforms in either the lateral/basolateral or apical plasma membrane domains. The β1 isoform was expressed in the lateral/basolateral plasma membranes in mostly large cylindrical cells, while β3 and α1 both were expressed with "reversed polarity" in the apical cell membrane in lower epithelial cells. The heterogeneous expression of Na/K-ATPase subunits substantiates earlier notions that the ES is a dynamic structure where epithelial cells show inverted epithelial transport. Dual absorption and secretion processes may regulate and maintain inner ear fluid homeostasis. These findings may shed new light on the etiology of endolymphatic hydrops and MD.

sted, utgiver, år, opplag, sider
Springer Nature, 2020
Emneord
Endolymphatic sac, Human, Na/K-ATPase, Reversed polarity, SIM
HSV kategori
Identifikatorer
urn:nbn:se:uu:diva-406751 (URN)10.1007/s00441-019-03106-7 (DOI)000495969500003 ()31713726 (PubMedID)
Tilgjengelig fra: 2020-03-11 Laget: 2020-03-11 Sist oppdatert: 2021-03-25bibliografisk kontrollert

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