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Kämpfe Nordström, CharlottaORCID iD iconorcid.org/0000-0001-5825-9160
Publications (9 of 9) Show all publications
Liu, W., Li, H., Kämpfe Nordström, C., Danckwardt-Lillieström, N., Agrawal, S., Ladak, H. M. & Rask-Andersen, H. (2024). Immuno-surveillance and protection of the human cochlea. Frontiers in Neurology, 15, Article ID 1355785.
Open this publication in new window or tab >>Immuno-surveillance and protection of the human cochlea
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2024 (English)In: Frontiers in Neurology, E-ISSN 1664-2295, Vol. 15, article id 1355785Article in journal (Refereed) Published
Abstract [en]

Background: Despite its location near infection-prone areas, the human inner ear demonstrates remarkable resilience. This suggests that there are inherent instruments deterring the invasion and spread of pathogens into the inner ear. Here, we combined high-resolution light microscopy, super-resolution immunohistochemistry (SR-SIM) and synchrotron phase contrast imaging (SR-PCI) to identify the protection and barrier systems in the various parts of the human inner ear, focusing on the lateral wall, spiral ganglion, and endolymphatic sac.

Materials and methods: Light microscopy was conducted on mid-modiolar, semi-thin sections, after direct glutaraldehyde/osmium tetroxide fixation. The tonotopic locations were estimated using SR-PCI and 3D reconstruction in cadaveric specimens. The sections were analyzed for leucocyte and macrophage activity, and the results were correlated with immunohistochemistry using confocal microscopy and SR-SIM.

Results: Light microscopy revealed unprecedented preservation of cell anatomy and several macrophage-like cells that were localized in the cochlea. Immunohistochemistry demonstrated IBA1 cells frequently co-expressing MHC II in the spiral ganglion, nerve fibers, lateral wall, spiral limbus, and tympanic covering layer at all cochlear turns as well as in the endolymphatic sac. RNAscope assays revealed extensive expression of fractalkine gene transcripts in type I spiral ganglion cells. CD4 and CD8 cells occasionally surrounded blood vessels in the modiolus and lateral wall. TMEM119 and P2Y12 were not expressed, indicating that the cells labeled with IBA1 were not microglia. The round window niche, compact basilar membrane, and secondary spiral lamina may form protective shields in the cochlear base.

Discussion: The results suggest that the human cochlea is surveilled by dwelling and circulating immune cells. Resident and blood-borne macrophages may initiate protective immune responses via chemokine signaling in the lateral wall, spiral lamina, and spiral ganglion at different frequency locations. Synchrotron imaging revealed intriguing protective barriers in the base of the cochlea. The role of the endolymphatic sac in human inner ear innate and adaptive immunity is discussed.

Place, publisher, year, edition, pages
Frontiers Media S.A., 2024
Keywords
human cochlea, IBA1, immuno-surveillance, super resolution microscopy, synchrotron phase-contrast imaging
National Category
Otorhinolaryngology Surgery
Identifiers
urn:nbn:se:uu:diva-531093 (URN)10.3389/fneur.2024.1355785 (DOI)001234599300001 ()38817543 (PubMedID)
Funder
Swedish Research Council, 2022-03339
Available from: 2024-06-13 Created: 2024-06-13 Last updated: 2024-06-13Bibliographically approved
Kämpfe Nordström, C., Li, H., Ladak, H. M., Agrawal, S. & Rask-Andersen, H. (2020). A Micro-CT and Synchrotron Imaging Study of the Human Endolymphatic Duct with Special Reference to Endolymph Outflow and Meniere's Disease. Scientific Reports, 10(1), Article ID 8295.
Open this publication in new window or tab >>A Micro-CT and Synchrotron Imaging Study of the Human Endolymphatic Duct with Special Reference to Endolymph Outflow and Meniere's Disease
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2020 (English)In: Scientific Reports, E-ISSN 2045-2322, Vol. 10, no 1, article id 8295Article in journal (Refereed) 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.

National Category
Medical Image Processing Biomedical Laboratory Science/Technology
Identifiers
urn:nbn:se:uu:diva-406752 (URN)10.1038/s41598-020-65110-0 (DOI)000540568100088 ()32427861 (PubMedID)
Funder
Swedish Research Council, 2017-03801
Note

De tre sista författarna delar sistaförfattarskapet

Available from: 2020-03-11 Created: 2020-03-11 Last updated: 2022-09-15Bibliographically approved
Kämpfe Nordström, C., Danckwardt-Lillieström, N., Liu, W. & Rask-Andersen, H. (2020). "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. Cell and Tissue Research, 379(3), 445-457
Open this publication in new window or tab >>"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 (English)In: Cell and Tissue Research, ISSN 0302-766X, E-ISSN 1432-0878, Vol. 379, no 3, p. 445-457Article in journal (Refereed) 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.

Place, publisher, year, edition, pages
Springer Nature, 2020
Keywords
Endolymphatic sac, Human, Na/K-ATPase, Reversed polarity, SIM
National Category
Cell and Molecular Biology
Identifiers
urn:nbn:se:uu:diva-406751 (URN)10.1007/s00441-019-03106-7 (DOI)000495969500003 ()31713726 (PubMedID)
Available from: 2020-03-11 Created: 2020-03-11 Last updated: 2021-03-25Bibliographically approved
Kämpfe Nordström, C. (2020). The Human Vestibular Aqueduct, Endolymphatic Duct and Sac: A Morphological Study Using Micro-CT, Super Resolution Immunohistochemistry and Synchrotron Phase Contrast Imaging. (Doctoral dissertation). Uppsala: Acta Universitatis Upsaliensis
Open this publication in new window or tab >>The Human Vestibular Aqueduct, Endolymphatic Duct and Sac: A Morphological Study Using Micro-CT, Super Resolution Immunohistochemistry and Synchrotron Phase Contrast Imaging
2020 (English)Doctoral thesis, comprehensive summary (Other academic)
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.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2020. p. 71
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1647
Keywords
Endolymphatic sac, endolymphatic duct, vestibular aqueduct, Meniere's disease, LVAS, micro-CT, synchrotron phase contrast imaging
National Category
Otorhinolaryngology
Research subject
Medical Science
Identifiers
urn:nbn:se:uu:diva-406848 (URN)978-91-513-0901-9 (ISBN)
Public defence
2020-05-07, Enghoffsalen, Akademiska sjukhuset, Ing 50, Uppsala, 09:00 (Swedish)
Opponent
Supervisors
Available from: 2020-04-16 Created: 2020-03-13 Last updated: 2020-05-19
Liu, W., Luque, M., Glueckert, R., Danckwardt-Lillieström, N., Kämpfe Nordström, C., Schrott-Fischer, A. & Rask-Andersen, H. (2019). Expression of Na/K-ATPase subunits in the human cochlea: a confocal and super-resolution microscopy study with special reference to auditory nerve excitation and cochlear implantation. Upsala Journal of Medical Sciences, 124(3), 168-179
Open this publication in new window or tab >>Expression of Na/K-ATPase subunits in the human cochlea: a confocal and super-resolution microscopy study with special reference to auditory nerve excitation and cochlear implantation
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2019 (English)In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 124, no 3, p. 168-179Article in journal (Refereed) Published
Abstract [en]

Background: For the first time the expression of the ion transport protein sodium/potassium-ATPase and its isoforms was analyzed in the human cochlea using light- and confocal microscopy as well as super-resolution structured illumination microscopy. It may increase our understanding of its role in the propagation and processing of action potentials in the human auditory nerve and how electric nerve responses are elicited from auditory prostheses.

Material and methods: Archival human cochlear sections were obtained from trans-cochlear surgeries. Antibodies against the Na/K-ATPase beta 1 isoform together with alpha 1 and alpha 3 were used for immunohistochemistry. An algorithm was applied to assess the expression in various domains.

Results: Na/K ATPase beta 1 subunit was expressed, mostly combined with the alpha 1 isoform. Neurons expressed the beta 1 subunit combined with alpha 3, while satellite glial cells expressed the alpha 1 isoform without recognized association with beta 1. Types I and II spiral ganglion neurons and efferent fibers expressed the Na/K-ATPase alpha 3 subunit. Inner hair cells, nerve fibers underneath, and efferent and afferent fibers in the organ of Corti also expressed alpha 1. The highest activity of Na/K-ATPase beta 1 was at the inner hair cell/nerve junction and spiral prominence.

Conclusion: The human auditory nerve displays distinct morphologic features represented in its molecular expression. It was found that electric signals generated via hair cells may not go uninterrupted across the spiral ganglion, but are locally processed. This may be related to particular filtering properties in the human acoustic pathway.

Place, publisher, year, edition, pages
TAYLOR & FRANCIS LTD, 2019
Keywords
Auditory nerve, cochlea, human, Na, K-ATPase, structured illumination microscopy
National Category
Neurosciences
Identifiers
urn:nbn:se:uu:diva-396105 (URN)10.1080/03009734.2019.1653408 (DOI)000484398600001 ()31460814 (PubMedID)
Available from: 2019-11-01 Created: 2019-11-01 Last updated: 2019-11-01Bibliographically approved
Liu, W., Kämpfe Nordström, C., Danckwardt-Lillieström, N. & Rask-Andersen, H. (2019). Human Inner Ear Immune Activity: A Super-Resolution Immunohistochemistry Study. Frontiers in Neurology, 10, Article ID 728.
Open this publication in new window or tab >>Human Inner Ear Immune Activity: A Super-Resolution Immunohistochemistry Study
2019 (English)In: Frontiers in Neurology, E-ISSN 1664-2295, Vol. 10, article id 728Article in journal (Refereed) Published
Abstract [en]

Background: Like the brain, the human inner ear was long thought to be devoid of immune activity. Only the endolymphatic sac (ES) was known to be endowed with white blood cells that could process antigens and serve as an immunologic defense organ for the entire inner ear. Unexpectedly, the cochlear and vestibular organs, including the eighth cranial nerve, were recently shown to contain macrophages whose functions and implication in ear disease are somewhat undefined. Here, we review recent inner ear findings in man and extend the analyses to the vestibular nerve using super-resolution structured illumination microscopy (SR-SIM).

Materials and Methods: Human ESs and cochleae were collected during surgery to treat patients with vestibular schwannoma and life-threatening petro-clival meningioma compressing the brainstem. The ESs and cochleae were placed in fixative, decalcified, and rapidly frozen and cryostat sectioned. Antibodies against ionized calcium-binding adaptor molecule 1-expressing cells (IBA1 cells), laminin beta 2 and type IV collagen TUJ1, cytokine fractalkine (CX3CL1), toll-like receptor 4 (TLR4), CD68, CD11b, CD4, CD8, the major histocompatibility complex type II (MHCII), and the microglial marker TEME119 were used.

Results: IBA1-positive cells were present in the ESs, the cochlea, central and peripheral axons of the cochlear nerve, and the vestibular nerve trunk. IBA1 cells were found in the cochlear lateral wall, spiral limbus, and spiral ganglion. Notable variants of IBA1 cells adhered to neurons with "synapse-like" specializations and cytoplasmic projections. Slender IBA1 cells occasionally protracted into the basal lamina of the Schwann cells and had intimate contact with surrounding axons.

Discussion: The human eighth nerve may be under the control of a well-developed macrophage cell system. A small number of CD4+ and CD8+ cells were found in the ES and occasionally in the cochlea, mostly located in the peripheral region of Rosenthal's canal. A neuro-immunologic axis may exist in the human inner ear that could play a role in the protection of the auditory nerve. The implication of the macrophage system during disease, surgical interventions, and cell-based transplantation should be further explored.

Place, publisher, year, edition, pages
FRONTIERS MEDIA SA, 2019
Keywords
human, inner ear, IBA1, macrophages, structured illumination microscopy
National Category
Neurosciences Otorhinolaryngology
Identifiers
urn:nbn:se:uu:diva-390794 (URN)10.3389/fneur.2019.00728 (DOI)000474785100001 ()31354608 (PubMedID)
Available from: 2019-08-14 Created: 2019-08-14 Last updated: 2023-08-28Bibliographically approved
Kämpfe Nordström, C., Danckwardt-Lillieström, N., Laurell, G., Liu, W. & Rask-Andersen, H. (2019). The Human Endolymphatic Sac and Inner Ear Immunity: Macrophage Interaction and Molecular Expression. Frontiers in Immunology, 9, Article ID 3181.
Open this publication in new window or tab >>The Human Endolymphatic Sac and Inner Ear Immunity: Macrophage Interaction and Molecular Expression
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2019 (English)In: Frontiers in Immunology, E-ISSN 1664-3224, Vol. 9, article id 3181Article in journal (Refereed) 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.

Keywords
human, cochlea, macrophages, IBA1, structured illumination microscopy
National Category
Otorhinolaryngology Immunology in the medical area
Identifiers
urn:nbn:se:uu:diva-377333 (URN)10.3389/fimmu.2018.03181 (DOI)000457362000001 ()30774637 (PubMedID)
Available from: 2019-02-25 Created: 2019-02-25 Last updated: 2024-01-17Bibliographically approved
Kämpfe Nordström, C., Laurell, G. & Rask-Andersen, H. (2016). The Human Vestibular Aqueduct: Anatomical Characteristics and Enlargement Criteria. Otology and Neurotology, 37(10), 1637-1645
Open this publication in new window or tab >>The Human Vestibular Aqueduct: Anatomical Characteristics and Enlargement Criteria
2016 (English)In: Otology and Neurotology, ISSN 1531-7129, E-ISSN 1537-4505, Vol. 37, no 10, p. 1637-1645Article in journal (Refereed) 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.

Keywords
LVAS, Pendrin, SLC26A4, Vestibular aqueduct
National Category
Otorhinolaryngology
Identifiers
urn:nbn:se:uu:diva-311179 (URN)10.1097/MAO.0000000000001203 (DOI)000388185000036 ()27631836 (PubMedID)
Available from: 2016-12-22 Created: 2016-12-22 Last updated: 2020-03-13Bibliographically approved
Idrizbegovic, E., Hederstierna, C., Dahlquist, M., Kämpfe Nordström, C., Jelic, V. & Rosenhall, U. (2011). Central auditory function in early Alzheimer's disease and in mild cognitive impairment.. Age and Ageing, 40(2)
Open this publication in new window or tab >>Central auditory function in early Alzheimer's disease and in mild cognitive impairment.
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2011 (English)In: Age and Ageing, ISSN 0002-0729, E-ISSN 1468-2834, Vol. 40, no 2Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE: to investigate auditory function in subjects with early Alzheimer's disease, mild cognitive impairment and with subjective memory complaints, in search of signs of central auditory processing dysfunction even in early stages of cognitive impairment.

DESIGN AND SUBJECTS: a consecutive group of men and women, referred to the Memory Clinic at the Karolinska University Hospital, was approached for inclusion in this prospective study. One hundred and thirty-six subjects, mean age 64 years (range 50-78 years), diagnosed with Alzheimer's disease (n = 43), mild cognitive impairment (n = 59) or with subjective memory complaints (n = 34), were included.

METHODS: auditory function was assessed with pure tone audiometry, speech perception in quiet and in background noise and dichotic digits tests with two or three digits.

RESULTS: pure tone audiometry and speech perception scores in quiet and in background noise were normal for age and without between-group differences. Dichotic digits tests showed strongly significant differences between the three groups, where the Alzheimer's disease group performed significantly poorer than the other two groups, with the mild cognitive impairment group in an intermediate position.

CONCLUSIONS: our results demonstrate that central auditory processing dysfunction is highly evident in subjects with Alzheimer's disease, and to a considerable extent even in subjects with mild cognitive impairment.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-269484 (URN)10.1093/ageing/afq168 (DOI)21233090 (PubMedID)
Available from: 2015-12-16 Created: 2015-12-16 Last updated: 2017-12-01
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ORCID iD: ORCID iD iconorcid.org/0000-0001-5825-9160

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