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  1. Article ; Online: Deciphering the heterogeneity of myeloid cells during neuroinflammation in the single-cell era.

    Borst, Katharina / Prinz, Marco

    Brain pathology (Zurich, Switzerland)

    2020  Volume 30, Issue 6, Page(s) 1192–1207

    Abstract: Multiple sclerosis (MS) is a disabling neuroinflammatory disease, which is little understood and lacks a sufficient therapeutic regimen. Myeloid cells have repeatedly shown to play a pivotal role in the disease progression. During homeostasis, only the ... ...

    Abstract Multiple sclerosis (MS) is a disabling neuroinflammatory disease, which is little understood and lacks a sufficient therapeutic regimen. Myeloid cells have repeatedly shown to play a pivotal role in the disease progression. During homeostasis, only the CNS-resident microglia and CNS-associated macrophages are present in the CNS. Neuroinflammation causes peripheral immune cells to infiltrate the CNS contributing to disease progression and neurological sequelae. The differential involvement of the diverse peripheral and resident myeloid cell subsets to the disease pathogenesis and outcome are highly debated and difficult to assess. However, novel technological advances (new mouse models, single-cell RNA-Sequencing, and CYTOF) have improved the depth of immune profiling, which allows the characterization of distinct myeloid subsets. This review provides an overview of current knowledge on the phenotypes and roles of these different myeloid subsets in neuroinflammatory disease and their therapeutic relevance.
    MeSH term(s) Animals ; Brain/pathology ; Inflammation/pathology ; Macrophages/pathology ; Microglia/pathology ; Myeloid Cells/pathology ; Single-Cell Analysis
    Language English
    Publishing date 2020-11-06
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1051484-3
    ISSN 1750-3639 ; 1015-6305
    ISSN (online) 1750-3639
    ISSN 1015-6305
    DOI 10.1111/bpa.12910
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    Zs.A 3585: Show issues Location:
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  2. Article ; Online: Microglia: Immune and non-immune functions.

    Borst, Katharina / Dumas, Anaelle Aurelie / Prinz, Marco

    Immunity

    2021  Volume 54, Issue 10, Page(s) 2194–2208

    Abstract: As resident macrophages of the central nervous system (CNS), microglia are associated with diverse functions essential to the developing and adult brain during homeostasis and disease. They are aided in their tasks by intricate bidirectional ... ...

    Abstract As resident macrophages of the central nervous system (CNS), microglia are associated with diverse functions essential to the developing and adult brain during homeostasis and disease. They are aided in their tasks by intricate bidirectional communication with other brain cells under steady-state conditions as well as with infiltrating peripheral immune cells during perturbations. Harmonious cell-cell communication involving microglia are considered crucial to maintain the healthy state of the tissue environment and to overcome pathology such as neuroinflammation. Analyses of such intercellular pathways have contributed to our understanding of the heterogeneous but context-associated microglial responses to environmental cues across neuropathology, including inflammatory conditions such as infections and autoimmunity, as well as immunosuppressive states as seen in brain tumors. Here, we summarize the latest evidence demonstrating how these interactions drive microglia immune and non-immune functions, which coordinate the transition from homeostatic to disease-related cellular states.
    MeSH term(s) Animals ; Central Nervous System/cytology ; Central Nervous System/physiology ; Homeostasis/physiology ; Humans ; Microglia/cytology ; Microglia/physiology
    Language English
    Publishing date 2021-10-10
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 1217235-2
    ISSN 1097-4180 ; 1074-7613
    ISSN (online) 1097-4180
    ISSN 1074-7613
    DOI 10.1016/j.immuni.2021.09.014
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    Zs.MG 69: Show issues

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  3. Article ; Online: Current tools to interrogate microglial biology.

    Dumas, Anaelle Aurelie / Borst, Katharina / Prinz, Marco

    Neuron

    2021  Volume 109, Issue 18, Page(s) 2805–2819

    Abstract: Microglial cells perform a plethora of functions in the central nervous system (CNS), involving them in brain development, maintenance of homeostasis in adulthood, and CNS diseases. Significant technical advancements have prompted the development of ... ...

    Abstract Microglial cells perform a plethora of functions in the central nervous system (CNS), involving them in brain development, maintenance of homeostasis in adulthood, and CNS diseases. Significant technical advancements have prompted the development of novel systems adapted to analyze microglia with increasing specificity and intricacy. The advent of single-cell technologies combined with targeted mouse models has been decisive in deciphering microglia heterogeneity and dissecting microglial functions. However sophisticated these tools have become, clear limitations remain. Understanding their pitfalls and advantages ensures their correct application. Therefore, we provide a guide to the cutting-edge methods currently available to dissect microglial biology.
    MeSH term(s) Animals ; Brain/physiology ; Central Nervous System Diseases/diagnosis ; Central Nervous System Diseases/genetics ; Central Nervous System Diseases/metabolism ; Gene Expression Profiling/methods ; Humans ; Metabolomics/methods ; Microglia/physiology ; Neurons/physiology ; Proteomics/methods
    Language English
    Publishing date 2021-08-13
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 808167-0
    ISSN 1097-4199 ; 0896-6273
    ISSN (online) 1097-4199
    ISSN 0896-6273
    DOI 10.1016/j.neuron.2021.07.004
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    Zs.A 2496: Show issues Location:
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    Zs.MG 92: Show issues

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  4. Conference proceedings: Auswirkung der Kraftsteigerung des Musculus supraspinatus und der vollständigen Resektion des Ligamentum coracoacromiale auf den subakromialen Druck – eine in vitro Schulter-Studie

    Borst, Katharina / Santos, Inês / Müller, Peter / Chevalier, Yan / Pietschmann, Matthias

    2022  , Page(s) AB48–179

    Event/congress Deutscher Kongress für Orthopädie und Unfallchirurgie (DKOU 2022); Berlin; ; Berufsverband für Orthopädie und Unfallchirurgie; 2022
    Keywords Medizin, Gesundheit ; Schulter ; Arthroskopische subacromiale Dekompression Subakromialer Druck ; Musculus supraspinatus ; Resektion Ligamentum coracoacromiale ; Subakromiales Impingement
    Publishing date 2022-10-25
    Publisher German Medical Science GMS Publishing House; Düsseldorf
    Document type Conference proceedings
    DOI 10.3205/22dkou352
    Database German Medical Science

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  5. Article ; Online: Reply to: "Unveiling the depletion of Kupffer cells in experimental hepatocarcinogenesis through liver macrophage subtype-specific markers".

    Borst, Katharina / Graalmann, Theresa / Kalinke, Ulrich

    Journal of hepatology

    2019  Volume 71, Issue 3, Page(s) 633–635

    MeSH term(s) Animals ; Carcinogenesis ; Hepatitis ; Kupffer Cells ; Liver ; Receptor, Interferon alpha-beta
    Chemical Substances Receptor, Interferon alpha-beta (156986-95-7)
    Language English
    Publishing date 2019-06-18
    Publishing country Netherlands
    Document type Letter ; Comment
    ZDB-ID 605953-3
    ISSN 1600-0641 ; 0168-8278
    ISSN (online) 1600-0641
    ISSN 0168-8278
    DOI 10.1016/j.jhep.2019.05.012
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    Zs.A 2027: Show issues Location:
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  6. Article ; Online: Reply to: "Lack of Kupffer cell depletion in diethylnitrosamine-induced hepatic inflammation".

    Borst, Katharina / Graalmann, Theresa / Kalinke, Ulrich

    Journal of hepatology

    2019  Volume 70, Issue 4, Page(s) 815–816

    MeSH term(s) Diethylnitrosamine ; Hepatitis ; Humans ; Inflammation ; Kupffer Cells ; Receptor, Interferon alpha-beta
    Chemical Substances Receptor, Interferon alpha-beta (156986-95-7) ; Diethylnitrosamine (3IQ78TTX1A)
    Language English
    Publishing date 2019-02-01
    Publishing country Netherlands
    Document type Letter ; Comment
    ZDB-ID 605953-3
    ISSN 1600-0641 ; 0168-8278
    ISSN (online) 1600-0641
    ISSN 0168-8278
    DOI 10.1016/j.jhep.2018.12.034
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    Zs.A 2027: Show issues Location:
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  7. Article ; Online: Microglia metabolism in health and disease.

    Borst, Katharina / Schwabenland, Marius / Prinz, Marco

    Neurochemistry international

    2018  Volume 130, Page(s) 104331

    Abstract: In the last decade tremendous progress has been made in understanding how the immune system reacts to insults. During this progress it became obvious that those immune responses are tightly regulated and cross-linked with distinct metabolic changes in ... ...

    Abstract In the last decade tremendous progress has been made in understanding how the immune system reacts to insults. During this progress it became obvious that those immune responses are tightly regulated and cross-linked with distinct metabolic changes in immune cells. Extensive research has been conducted mainly on subtypes of T cells, which use different metabolic pathways during differentiation processes and activation states. In addition, it has also been established later, that the innate immune cell lineage of myeloid cells includes a variety of different subsets of bone marrow-derived as well as tissue-specific macrophages, which elicit much more functions than simply killing bacteria. To execute this high variety of functions, also macrophages use different metabolic pathways and are tightly regulated by key metabolic regulators, such as the mechanistic target of rapamycin (mTOR). Upon activation, metabolic changes within the cell occur to meet the requirements of the phenotypic switch. In addition, metabolic changes correlate with the ability of innate immune cells to show hallmarks of adaptive immune responses. Little is known about specific metabolic changes of myeloid cells and specifically microglia in vivo. Microglia are key players in neurodegenerative and neuroinflammatory diseases and have become a major target of medical research. Here, we review the existing data on microglia metabolism and the connection of microglia phenotypes with neuroinflammatory and neurodegenerative diseases. Lastly, we will discuss how our knowledge about the cellular metabolism might be used to develop new treatment options for neurological diseases.
    MeSH term(s) Animals ; Brain/metabolism ; Brain/pathology ; Energy Metabolism/physiology ; Humans ; Inflammation/metabolism ; Inflammation/pathology ; Microglia/metabolism ; Microglia/pathology ; Neurodegenerative Diseases/metabolism ; Neurodegenerative Diseases/pathology
    Language English
    Publishing date 2018-11-10
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 283190-9
    ISSN 1872-9754 ; 0197-0186
    ISSN (online) 1872-9754
    ISSN 0197-0186
    DOI 10.1016/j.neuint.2018.11.006
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    Zs.A 1610: Show issues Location:
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  8. Article ; Online: Insulin-like growth factor-1 receptor controls the function of CNS-resident macrophages and their contribution to neuroinflammation.

    Ivan, Daniela C / Berve, Kristina Carolin / Walthert, Sabrina / Monaco, Gianni / Borst, Katharina / Bouillet, Elisa / Ferreira, Filipa / Lee, Henry / Steudler, Jasmin / Buch, Thorsten / Prinz, Marco / Engelhardt, Britta / Locatelli, Giuseppe

    Acta neuropathologica communications

    2023  Volume 11, Issue 1, Page(s) 35

    Abstract: Signaling by insulin-like growth factor-1 (IGF-1) is essential for the development of the central nervous system (CNS) and regulates neuronal survival and myelination in the adult CNS. In neuroinflammatory conditions including multiple sclerosis (MS) and ...

    Abstract Signaling by insulin-like growth factor-1 (IGF-1) is essential for the development of the central nervous system (CNS) and regulates neuronal survival and myelination in the adult CNS. In neuroinflammatory conditions including multiple sclerosis (MS) and its animal model experimental autoimmune encephalomyelitis (EAE), IGF-1 can regulate cellular survival and activation in a context-dependent and cell-specific manner. Notwithstanding its importance, the functional outcome of IGF-1 signaling in microglia/macrophages, which maintain CNS homeostasis and regulate neuroinflammation, remains undefined. As a result, contradictory reports on the disease-ameliorating efficacy of IGF-1 are difficult to interpret, together precluding its potential use as a therapeutic agent. To fill this gap, we here investigated the role of IGF-1 signaling in CNS-resident microglia and border associated macrophages (BAMs) by conditional genetic deletion of the receptor Igf1r in these cell types. Using a series of techniques including histology, bulk RNA sequencing, flow cytometry and intravital imaging, we show that absence of IGF-1R significantly impacted the morphology of both BAMs and microglia. RNA analysis revealed minor changes in microglia. In BAMs however, we detected an upregulation of functional pathways associated with cellular activation and a decreased expression of adhesion molecules. Notably, genetic deletion of Igf1r from CNS-resident macrophages led to a significant weight gain in mice, suggesting that absence of IGF-1R from CNS-resident myeloid cells indirectly impacts the somatotropic axis. Lastly, we observed a more severe EAE disease course upon Igf1r genetic ablation, thus highlighting an important immunomodulatory role of this signaling pathway in BAMs/microglia. Taken together, our work shows that IGF-1R signaling in CNS-resident macrophages regulates the morphology and transcriptome of these cells while significantly decreasing the severity of autoimmune CNS inflammation.
    MeSH term(s) Animals ; Mice ; Central Nervous System/metabolism ; Central Nervous System/pathology ; Encephalomyelitis, Autoimmune, Experimental/metabolism ; Encephalomyelitis, Autoimmune, Experimental/pathology ; Insulin-Like Growth Factor I/metabolism ; Macrophages/metabolism ; Mice, Inbred C57BL ; Microglia/metabolism ; Multiple Sclerosis/pathology ; Neuroinflammatory Diseases
    Chemical Substances Insulin-Like Growth Factor I (67763-96-6)
    Language English
    Publishing date 2023-03-08
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2715589-4
    ISSN 2051-5960 ; 2051-5960
    ISSN (online) 2051-5960
    ISSN 2051-5960
    DOI 10.1186/s40478-023-01535-8
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  9. Article ; Online: Higher patient knowledge and resilience improve the functional outcome of primary total knee arthroplasty.

    Bumberger, Alexander / Borst, Katharina / Hobusch, Gerhard M / Willegger, Madeleine / Stelzeneder, David / Windhager, Reinhard / Domayer, Stephan / Waldstein, Wenzel

    Wiener klinische Wochenschrift

    2021  Volume 133, Issue 11-12, Page(s) 543–549

    Abstract: Background: A significant percentage of patients have an unfavorable outcome following primary total knee arthroplasty (TKA). This study aimed to evaluate whether specific knowledge about the implant and resilience can influence the functional outcome ... ...

    Abstract Background: A significant percentage of patients have an unfavorable outcome following primary total knee arthroplasty (TKA). This study aimed to evaluate whether specific knowledge about the implant and resilience can influence the functional outcome following TKA.
    Methods: A consecutive series of 163 patients following primary TKA at a mean age of 70 years (SD 9.1 years) were included at a regional rehabilitation center between December 2015 and December 2016. Specific patient knowledge (scale 0-7), Connor Davidson Resilience Scale (CD-RISC), Western Ontario and McMaster Universities (WOMAC) score, University of California and Los Angeles (UCLA) score and constitutional parameters were assessed on admission. Pearson's correlation analysis and stepwise linear regression analysis were performed to investigate associations between knowledge, resilience and functional scores.
    Results: The mean overall knowledge score was 3.5 out of 7 and the mean resilience score was 72.9 out of 100. Mean WOMAC and UCLA scores on admission were 23.8 and 5.5, respectively. Stepwise linear regression analysis identified knowledge and age as significant predictors of WOMAC scores (R
    Conclusion: This study highlights the importance of patient-related factors as part of an integral patient care concept in TKA. Although the identified predictors still need to be refined, it could be demonstrated how better patient knowledge might ultimately lead to better functional outcome following TKA. Routinely assessing patients' resilience might be a useful tool to identify patients at risk for low activity levels.
    Level of evidence: III. Patient-reported outcome study.
    MeSH term(s) Aged ; Arthroplasty, Replacement, Knee ; Humans ; Knee Joint/surgery ; Osteoarthritis, Knee/surgery ; Retrospective Studies ; Treatment Outcome
    Language English
    Publishing date 2021-03-19
    Publishing country Austria
    Document type Journal Article
    ZDB-ID 200462-8
    ISSN 1613-7671 ; 0043-5325 ; 0300-5178
    ISSN (online) 1613-7671
    ISSN 0043-5325 ; 0300-5178
    DOI 10.1007/s00508-021-01829-8
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    Zs.A 902: Show issues Location:
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  10. Article ; Online: Specific knowledge and resilience affect short-term outcome in patients following primary total hip arthroplasty.

    Bumberger, Alexander / Borst, Katharina / Willegger, Madeleine / Hobusch, Gerhard M / Windhager, Reinhard / Waldstein, Wenzel / Domayer, Stephan

    Archives of orthopaedic and trauma surgery

    2021  Volume 142, Issue 6, Page(s) 1229–1237

    Abstract: Purpose: The aim of the present study was to investigate the potential associations between specific knowledge, resilience and patient-reported outcome measures (PROMS) following primary total hip arthroplasty (THA).: Methods: In a cross-sectional ... ...

    Abstract Purpose: The aim of the present study was to investigate the potential associations between specific knowledge, resilience and patient-reported outcome measures (PROMS) following primary total hip arthroplasty (THA).
    Methods: In a cross-sectional prospective study, consecutive patients following primary THA were included at a rehabilitation center. A novel knowledge score and the validated Connor Davidson Resilience Scale (CD-RISC) were utilized to assess patients' specific knowledge and resilience, respectively. Additionally, patients completed a qualitative questionnaire regarding the information they had received. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), as well as the University of California and Los Angeles Score (UCLA) served as primary outcome measures. Stepwise multiple regression analysis was performed to identify potential predictors of outcome.
    Results: A total of 103 patients at a mean age of 67.5 years (SD 10.5, 38-88) were included in the analysis at a median of 55.5 days (IQR 43-81) following primary THA. The mean knowledge and resilience scores were 3.8 (SD 1.6, 0-7) and 69.5 (SD 18.5, 0-100), respectively. Forty-seven percent of patients were afraid of harming their prosthesis and these patients had up to 59% worse WOMAC scores (p < 0.001). WOMAC scores on admission to rehabilitation were predicted by resilience and knowledge scores (R
    Conclusion: The present study demonstrated that patients with a feeling of uncertainty had an inferior short-term functional outcome following primary THA. Moreover, it could be shown that higher specific knowledge and resilience are associated with a better functional outcome according to validated PROMS. While these findings need to be prospectively validated in future studies, specific patient knowledge and resilience may have a direct impact on the outcome of primary THA.
    MeSH term(s) Adult ; Aged ; Aged, 80 and over ; Arthroplasty, Replacement, Hip ; Cross-Sectional Studies ; Health Knowledge, Attitudes, Practice ; Humans ; Middle Aged ; Prospective Studies ; Resilience, Psychological ; Treatment Outcome
    Language English
    Publishing date 2021-06-03
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 80407-1
    ISSN 1434-3916 ; 0003-9330 ; 0344-8444
    ISSN (online) 1434-3916
    ISSN 0003-9330 ; 0344-8444
    DOI 10.1007/s00402-021-03967-0
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