66 results on '"Wälchli, T"'
Search Results
2. Endovascular Management of Intracranial Dural AVFs: Transvenous Approach
- Author
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Bhatia, K.D., primary, Lee, H., additional, Kortman, H., additional, Klostranec, J., additional, Guest, W., additional, Wälchli, T., additional, Radovanovic, I., additional, Krings, T., additional, and Pereira, V.M., additional
- Published
- 2021
- Full Text
- View/download PDF
3. Endovascular Management of Intracranial Dural Arteriovenous Fistulas: Transarterial Approach
- Author
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Bhatia, K.D., primary, Lee, H., additional, Kortman, H., additional, Klostranec, J., additional, Guest, W., additional, Wälchli, T., additional, Radovanovic, I., additional, Krings, T., additional, and Pereira, V.M., additional
- Published
- 2021
- Full Text
- View/download PDF
4. Endovascular Management of Intracranial Dural AVFs: Transvenous Approach.
- Author
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Bhatia, K. D., Lee, H., Kortman, H., Klostranec, J., Guest, W., Wälchli, T., Radovanovic, I., Krings, T., and Pereira, V. M.
- Published
- 2022
- Full Text
- View/download PDF
5. Endovascular Management of Intracranial Dural Arteriovenous Fistulas: Transarterial Approach.
- Author
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Bhatia, K. D., Lee, H., Kortman, H., Klostranec, J., Guest, W., Wälchli, T., Radovanovic, I., Krings, T., and Pereira, V. M.
- Published
- 2022
- Full Text
- View/download PDF
6. Endovascular Management of Intracranial Dural AVFs: Principles.
- Author
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Bhatia, K. D., Lee, H., Kortman, H., Klostranec, J., Guest, W., Wälchli, T., Radovanovic, I., Krings, T., and Pereira, V. M.
- Published
- 2022
- Full Text
- View/download PDF
7. Artery of Davidoff and Schechter Supply in Dural Arteriovenous Fistulas
- Author
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Bhatia, K.D., primary, Kortman, H., additional, Wälchli, T., additional, Radovanovic, I., additional, Pereira, V.M., additional, and Krings, T., additional
- Published
- 2020
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- View/download PDF
8. Translation laboratory: Oskar Pastior’s applied translation research
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Caduff, Corina, Wälchli, Tan, Caduff, C ( Corina ), Wälchli, T ( Tan ), Strässle, Thomas, Caduff, Corina, Wälchli, Tan, Caduff, C ( Corina ), Wälchli, T ( Tan ), and Strässle, Thomas
- Abstract
In his intonations to a poem by Charles Baudelaire, which appeared in 2002 under the title o du roher iasmin, Oskar Pastior conducts a piece of applied translation research. He meets the challenges of literary translation, as they are most prominently shown in lyrics, in a translation laboratory in which, in 43 attempts, the different sides of the Baudelaire poem are set out and examined. The act of translating is methodically segmented and explored regarding its latitude, and it is systematically and polyperspectively put in reference to the many different aspects of the body of language. By serialising the individual attempts, the literary text gains an argumentative structure that makes it readable as artistic research: it produces aesthetic knowledge in artistic practice.
- Published
- 2019
9. Nogo-A and S1PR2 as novel regulators of developmental and tumor angiogenesis in the CNS
- Author
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Wälchli, T, Schwab, ME, Weller, M, Bozinov, O, Regli, L, and Hoerstrup, SP
- Subjects
ddc: 610 ,genetic structures ,Angiogenesis ,Nogo-A ,610 Medical sciences ,Medicine ,Glioblastoma ,eye diseases ,nervous system diseases - Abstract
Objective: One hallmark of glioblastoma (GBM) growth is angiogenesis, the growth of blood vessels. Classical approaches to target glioblastoma angiogenesis – for instance using the anti-VEGF-A antibody bevacizumab/Avastin® – have not led to the desired improvement of patient [for full text, please go to the a.m. URL], 67. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), 1. Joint Meeting mit der Koreanischen Gesellschaft für Neurochirurgie (KNS)
- Published
- 2016
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10. Efficacy of Intraoperative Epidural Triamcinolone (Kenacort®) Application in Lumbar Microdiscectomy: A Matched-Control Study
- Author
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Stienen, M.N., additional, Neidert, M.C., additional, Bellut, D., additional, Wälchli, T., additional, Regli, L., additional, Schaller, K., additional, and Gautschi, O.P., additional
- Published
- 2017
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11. Characterization of angiogenesis and the neurovascular unit in chronic subdural hematoma
- Author
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Wälchli, T, Burkhardt, JK, Neidert, MC, Regli, L, Hoerstrup, SP, Bozinov, O, Wälchli, T, Burkhardt, JK, Neidert, MC, Regli, L, Hoerstrup, SP, and Bozinov, O
- Published
- 2016
12. The CXCL12/CXCR4/CXCR7 ligand-receptor system regulates neuro-glio-vascular interactions and vessel growth during human brain development
- Author
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Virgintino, D, Errede, M, Girolamo, F, Strippoli, M, Wälchli, T, Robertson, D, Frei, K, Roncali, L, University of Zurich, and Virgintino, D
- Subjects
10180 Clinic for Neurosurgery ,2716 Genetics (clinical) ,1311 Genetics ,610 Medicine & health - Published
- 2013
13. Expression of nogo-a is decreased with increasing gestational age in the human fetal brain
- Author
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Haybaeck, J, Lienos, I C, Dulay, R J, Bettermann, K, Miller, C L, Wälchli, T, Frei, K, Virgintino, D, Rizzi, M, Weis, S, Haybaeck, J, Lienos, I C, Dulay, R J, Bettermann, K, Miller, C L, Wälchli, T, Frei, K, Virgintino, D, Rizzi, M, and Weis, S
- Abstract
Nogo is a member of the reticulon family. Our understanding of the physiological functions of the Nogo-A protein has grown over the last few years, and this molecule is now recognized as one of the most important axonal regrowth inhibitors present in central nervous system (CNS) myelin. Nogo-A plays other important roles in nervous system development, epilepsy, vascular physiology, muscle pathology, stroke, inflammation, and CNS tumors. Since the exact role of Nogo-A protein in human brain development is still poorly understood, we studied its cellular and regional distribution by immunohistochemistry in the frontal lobe of 30 human fetal brains. Nogo-A was expressed in the following cortical zones: ependyma, ventricular zone, subventricular zone, intermediate zone, subplate, cortical plate, and marginal zone. The number of positive cells decreased significantly with increasing gestational age in the subplate and marginal zone. Using different antibodies, changes in isoform expression and dimerization states could be shown between various cortical zones. The results demonstrate a significant change in the expression of Nogo-A during the development of the human brain. The effects of its time- and region-specific regulation have to be further studied in detail.
- Published
- 2012
14. Playgiarism Rules: Hermann Burgers Poetologie
- Author
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Hughes, Peter, Fries, Thomas, Wälchli, Tan, Hughes, P ( Peter ), Fries, T ( Thomas ), Wälchli, T ( Tan ), Zumsteg, Simon, Hughes, Peter, Fries, Thomas, Wälchli, Tan, Hughes, P ( Peter ), Fries, T ( Thomas ), Wälchli, T ( Tan ), and Zumsteg, Simon
- Published
- 2008
15. Verschriftete Bilder: Gottfried Kellers Bildpoetik im Prozess der Säkularisierung
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Hughes, Peter, Fries, Thomas, Wälchli, Tan, Hughes, P ( Peter ), Fries, T ( Thomas ), Wälchli, T ( Tan ), Amrein, Ursula, Hughes, Peter, Fries, Thomas, Wälchli, Tan, Hughes, P ( Peter ), Fries, T ( Thomas ), Wälchli, T ( Tan ), and Amrein, Ursula
- Published
- 2008
16. Von der Krise der Historie zum Prozess des Schreibens: Nietzsches zweite 'Unzeitgemässe Betrachtung'
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Hughes, Peter, Fries, Thomas, Wälchli, Tan, Hughes, P ( Peter ), Fries, T ( Thomas ), Wälchli, T ( Tan ), Most, Glenn, Hughes, Peter, Fries, Thomas, Wälchli, Tan, Hughes, P ( Peter ), Fries, T ( Thomas ), Wälchli, T ( Tan ), and Most, Glenn
- Published
- 2008
17. Vom Malen zum Schreiben: Gottfried Kellers Berliner Schreibunterlage
- Author
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Hughes, Peter, Fries, Thomas, Wälchli, Tan, Hughes, P ( Peter ), Fries, T ( Thomas ), Wälchli, T ( Tan ), Kasper, Monika, Hughes, Peter, Fries, Thomas, Wälchli, Tan, Hughes, P ( Peter ), Fries, T ( Thomas ), Wälchli, T ( Tan ), and Kasper, Monika
- Published
- 2008
18. The neutrino oscillation OPERA experiment Target Tracker
- Author
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Baussan, E., Borer, Kurt, Campagne, Jean Eric, Chon-Sen, Nathalie, Dracos, M., Gornushkin, Y., Guyonnet, Jean Louis, Janicsko Csathy, J., Jollet, C., Juget, Frédéric, Krasnoperov, Alexei, Krumstein, Z., Moser, U., Nozdrin, A., Olchevski, A., Sadovski, A., Vilain, Pierre, Wälchli, T., Wilquet, Gaston, Baussan, E., Borer, Kurt, Campagne, Jean Eric, Chon-Sen, Nathalie, Dracos, M., Gornushkin, Y., Guyonnet, Jean Louis, Janicsko Csathy, J., Jollet, C., Juget, Frédéric, Krasnoperov, Alexei, Krumstein, Z., Moser, U., Nozdrin, A., Olchevski, A., Sadovski, A., Vilain, Pierre, Wälchli, T., and Wilquet, Gaston
- Abstract
The main task of the Target Tracker of the long baseline neutrino oscillation OPERA experiment, is to locate in which of the target elementary constituents, the lead/emulsion bricks, the neutrino interactions have occurred and also to give calorimetric information about each event. The technology used consists in walls of two planes of long plastic scintillator strips, one per transverse direction. Wavelength shifting fibres collect the light signal emitted by the scintillator strips and guide it to both ends where it is read by multi-anode photomultiplier tubes. The Target Tracker is composed of 62 scintillating walls of a total surface of about 6000 m2. Each wall is made by assembling 4 horizontal and 4 vertical modules of 64.7 m long, scintillating strips. This detector has observed the first neutrino interactions during August 2006. In this paper we will describe all elements used for the construction and operation of this detector and we will also give its main characteristics. © 2007 Elsevier B.V. All rights reserved., SCOPUS: ar.j, info:eu-repo/semantics/published
- Published
- 2007
19. The OPERA experiment Target Tracker
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Adam, T., Baussan, E., Borer, Kurt, Campagne, J.E., Chon-Sen, Nathalie, de La Taille, Christophe, Dick, N., Dracos, M., Gaudiot, G., Goeltzenlichter, T., Gornushkin, Y., Grapton, J.N., Guyonnet, Jean Louis, Hess, M., Igersheim, R., Janicsko Csathy, J., Jollet, C., Juget, Frédéric, Kocher, H., Krasnoperov, Alexei, Krumstein, Z., Martin-Chassard, Gisèle, Moser, U., Nozdrin, A., Olchevski, A., Porokhovoi, Yu S., Raux, Ludovic, Sadovski, A., Schuler, Joachim, Schütz, Harald H.U., Schwab, Claude, Smolnikov, Anatoly, Van Beek, Guy, Vilain, Pierre, Wälchli, T., Wilquet, Gaston, Wurtz, Jacques, Adam, T., Baussan, E., Borer, Kurt, Campagne, J.E., Chon-Sen, Nathalie, de La Taille, Christophe, Dick, N., Dracos, M., Gaudiot, G., Goeltzenlichter, T., Gornushkin, Y., Grapton, J.N., Guyonnet, Jean Louis, Hess, M., Igersheim, R., Janicsko Csathy, J., Jollet, C., Juget, Frédéric, Kocher, H., Krasnoperov, Alexei, Krumstein, Z., Martin-Chassard, Gisèle, Moser, U., Nozdrin, A., Olchevski, A., Porokhovoi, Yu S., Raux, Ludovic, Sadovski, A., Schuler, Joachim, Schütz, Harald H.U., Schwab, Claude, Smolnikov, Anatoly, Van Beek, Guy, Vilain, Pierre, Wälchli, T., Wilquet, Gaston, and Wurtz, Jacques
- Abstract
The main task of the Target Tracker detector of the long baseline neutrino oscillation OPERA experiment is to locate in which of the target elementary constituents, the lead/emulsion bricks, the neutrino interactions have occurred and also to give calorimetric information about each event. The technology used consists in walls of two planes of plastic scintillator strips, one per transverse direction. Wavelength shifting fibres collect the light signal emitted by the scintillator strips and guide it to both ends where it is read by multi-anode photomultiplier tubes. All the elements used in the construction of this detector and its main characteristics are described. © 2007 Elsevier B.V. All rights reserved., SCOPUS: ar.j, info:eu-repo/semantics/published
- Published
- 2007
20. Expression of Nogo-A Is Decreased with Increasing Gestational Age in the Human Fetal Brain
- Author
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Haybaeck, J., primary, Llenos, I.C., additional, Dulay, R.J., additional, Bettermann, K., additional, Miller, C.L., additional, Wälchli, T., additional, Frei, K., additional, Virgintino, D., additional, Rizzi, M., additional, and Weis, S., additional
- Published
- 2012
- Full Text
- View/download PDF
21. The neutrino oscillation OPERA experiment Target Tracker
- Author
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Baussan, E., primary, Borer, K., additional, Campagne, J.-E., additional, Chon-Sen, N., additional, Dracos, M., additional, Gornushkin, Y., additional, Guyonnet, J.-L., additional, Janicsko Csathy, J., additional, Jollet, C., additional, Juget, F., additional, Krasnoperov, A., additional, Krumstein, Z., additional, Moser, U., additional, Nozdrin, A., additional, Olchevski, A., additional, Sadovski, A., additional, Vilain, P., additional, Wälchli, T., additional, and Wilquet, G., additional
- Published
- 2007
- Full Text
- View/download PDF
22. The OPERA experiment Target Tracker
- Author
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Adam, T., primary, Baussan, E., additional, Borer, K., additional, Campagne, J-E., additional, Chon-Sen, N., additional, de La Taille, C., additional, Dick, N., additional, Dracos, M., additional, Gaudiot, G., additional, Goeltzenlichter, T., additional, Gornushkin, Y., additional, Grapton, J-N., additional, Guyonnet, J-L., additional, Hess, M., additional, Igersheim, R., additional, Janicsko Csathy, J., additional, Jollet, C., additional, Juget, F., additional, Kocher, H., additional, Krasnoperov, A., additional, Krumstein, Z., additional, Martin-Chassard, G., additional, Moser, U., additional, Nozdrin, A., additional, Olchevski, A., additional, Porokhovoi, S., additional, Raux, L., additional, Sadovski, A., additional, Schuler, J., additional, Schütz, H-U., additional, Schwab, C., additional, Smolnikov, A., additional, Van Beek, G., additional, Vilain, P., additional, Wälchli, T., additional, Wilquet, G., additional, and Wurtz, J., additional
- Published
- 2007
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- View/download PDF
23. A novel automatic film changer for high-speed analysis of nuclear emulsions
- Author
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Borer, K., primary, Damet, J., additional, Hess, M., additional, Kreslo, I., additional, Moser, U., additional, Pretzl, K., additional, Savvinov, N., additional, Schütz, H.-U., additional, Wälchli, T., additional, and Weber, M., additional
- Published
- 2006
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24. Expression of Nogo-A Is Decreased with Increasing Gestational Age in the Human Fetal Brain.
- Author
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Haybaeck, J., Llenos, I.C., Dulay, R.J., Bettermann, K., Miller, C.L., Wälchli, T., Frei, K., Virgintino, D., Rizzi, M., and Weis, S.
- Abstract
Nogo is a member of the reticulon family. Our understanding of the physiological functions of the Nogo-A protein has grown over the last few years, and this molecule is now recognized as one of the most important axonal regrowth inhibitors present in central nervous system (CNS) myelin. Nogo-A plays other important roles in nervous system development, epilepsy, vascular physiology, muscle pathology, stroke, inflammation, and CNS tumors. Since the exact role of Nogo-A protein in human brain development is still poorly understood, we studied its cellular and regional distribution by immunohistochemistry in the frontal lobe of 30 human fetal brains. Nogo-A was expressed in the following cortical zones: ependyma, ventricular zone, subventricular zone, intermediate zone, subplate, cortical plate, and marginal zone. The number of positive cells decreased significantly with increasing gestational age in the subplate and marginal zone. Using different antibodies, changes in isoform expression and dimerization states could be shown between various cortical zones. The results demonstrate a significant change in the expression of Nogo-A during the development of the human brain. The effects of its time- and region-specific regulation have to be further studied in detail. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]
- Published
- 2013
- Full Text
- View/download PDF
25. Artistic Research and Literature
- Author
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Caduff, Corina and Wälchli, Tan
- Subjects
Literature and literary studies ,bic Book Industry Communication::D Literature & literary studies - Abstract
What is practice-based literary research? While literature as a discipline is currently not represented in the artistic research discourse, individual writers and scholars have ties to a variety of institutional constellations in which overlaps between literature, art, and research become manifest. 16 of them expand on their methodological approaches as well as their practice, and they analyse exemplary case studies.
- Published
- 2019
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26. Single-cell atlas of the human brain vasculature across development, adulthood and disease.
- Author
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Wälchli T, Ghobrial M, Schwab M, Takada S, Zhong H, Suntharalingham S, Vetiska S, Gonzalez DR, Wu R, Rehrauer H, Dinesh A, Yu K, Chen ELY, Bisschop J, Farnhammer F, Mansur A, Kalucka J, Tirosh I, Regli L, Schaller K, Frei K, Ketela T, Bernstein M, Kongkham P, Carmeliet P, Valiante T, Dirks PB, Suva ML, Zadeh G, Tabar V, Schlapbach R, Jackson HW, De Bock K, Fish JE, Monnier PP, Bader GD, and Radovanovic I
- Subjects
- Female, Humans, Male, Cell Communication, HLA-D Antigens metabolism, Adult, Health, Brain blood supply, Brain pathology, Brain embryology, Brain metabolism, Brain Neoplasms blood supply, Brain Neoplasms pathology, Endothelial Cells metabolism, Endothelial Cells pathology, Endothelial Cells cytology, Fetus blood supply, Fetus cytology, Fetus embryology, RNA-Seq, Single-Cell Gene Expression Analysis, Central Nervous System Vascular Malformations pathology
- Abstract
A broad range of brain pathologies critically relies on the vasculature, and cerebrovascular disease is a leading cause of death worldwide. However, the cellular and molecular architecture of the human brain vasculature remains incompletely understood
1 . Here we performed single-cell RNA sequencing analysis of 606,380 freshly isolated endothelial cells, perivascular cells and other tissue-derived cells from 117 samples, from 68 human fetuses and adult patients to construct a molecular atlas of the developing fetal, adult control and diseased human brain vasculature. We identify extensive molecular heterogeneity of the vasculature of healthy fetal and adult human brains and across five vascular-dependent central nervous system (CNS) pathologies, including brain tumours and brain vascular malformations. We identify alteration of arteriovenous differentiation and reactivated fetal as well as conserved dysregulated genes and pathways in the diseased vasculature. Pathological endothelial cells display a loss of CNS-specific properties and reveal an upregulation of MHC class II molecules, indicating atypical features of CNS endothelial cells. Cell-cell interaction analyses predict substantial endothelial-to-perivascular cell ligand-receptor cross-talk, including immune-related and angiogenic pathways, thereby revealing a central role for the endothelium within brain neurovascular unit signalling networks. Our single-cell brain atlas provides insights into the molecular architecture and heterogeneity of the developing, adult/control and diseased human brain vasculature and serves as a powerful reference for future studies., (© 2024. Crown.)- Published
- 2024
- Full Text
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27. The liver and muscle secreted HFE2-protein maintains central nervous system blood vessel integrity.
- Author
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Wang XF, Vigouroux R, Syonov M, Baglaenko Y, Nikolakopoulou AM, Ringuette D, Rus H, DiStefano PV, Dufour S, Shabanzadeh AP, Lee S, Mueller BK, Charish J, Harada H, Fish JE, Wither J, Wälchli T, Cloutier JF, Zlokovic BV, Carlen PL, and Monnier PP
- Subjects
- Animals, Female, Mice, Central Nervous System metabolism, Endothelial Cells metabolism, Liver metabolism, Muscles metabolism, Blood-Brain Barrier metabolism, Encephalomyelitis, Autoimmune, Experimental
- Abstract
Liver failure causes breakdown of the Blood CNS Barrier (BCB) leading to damages of the Central-Nervous-System (CNS), however the mechanisms whereby the liver influences BCB-integrity remain elusive. One possibility is that the liver secretes an as-yet to be identified molecule(s) that circulate in the serum to directly promote BCB-integrity. To study BCB-integrity, we developed light-sheet imaging for three-dimensional analysis. We show that liver- or muscle-specific knockout of Hfe2/Rgmc induces BCB-breakdown, leading to accumulation of toxic-blood-derived fibrinogen in the brain, lower cortical neuron numbers, and behavioral deficits in mice. Soluble HFE2 competes with its homologue RGMa for binding to Neogenin, thereby blocking RGMa-induced downregulation of PDGF-B and Claudin-5 in endothelial cells, triggering BCB-disruption. HFE2 administration in female mice with experimental autoimmune encephalomyelitis, a model for multiple sclerosis, prevented paralysis and immune cell infiltration by inhibiting RGMa-mediated BCB alteration. This study has implications for the pathogenesis and potential treatment of diseases associated with BCB-dysfunction., (© 2024. The Author(s).)
- Published
- 2024
- Full Text
- View/download PDF
28. Ultrasound-Targeted Microbubble Destruction Increases BBB Permeability and Promotes Stem Cell-Induced Regeneration of Stroke by Downregulating MMP8.
- Author
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Bai Y, Du Y, Yang Y, Wälchli T, Constanthin PE, and Li F
- Subjects
- Animals, Rats, Blood-Brain Barrier, Matrix Metalloproteinase 8, Microbubbles, Cerebral Infarction, Stem Cells, Brain Edema, Stroke therapy, Brain Ischemia
- Abstract
The objective of this study was to evaluate the feasibility, safety, and effectiveness of intravenous stem cell delivery utilizing ultrasound-targeted microbubble destruction (UTMD) in a rat model of middle cerebral artery occlusion (MCAO), while investigating the underlying mechanisms. Acute cerebral infarction (ACI) was induced surgically in adult rats to create the MCAO rat model. Intravenous injection of SonoVue microbubbles and bone marrow-derived mesenchymal stem cells (BMSC) was performed concurrently, with or without ultrasound targeting the stroke. The animals were divided into four groups: sham-operated group, ACI-MCAO rats treated with phosphate-buffered saline (ACI+PBS), rats receiving intravenous delivery of BMSC expressing green fluorescent protein (GFP-BMSC; ACI+BMSC), and rats receiving intravenous GFP-BMSC with simultaneous UTMD exposure (ACI+BMSC+UTMD). The efficacy of the treatments was assessed by evaluating the animals' neurological function using the Longa score and examining histopathological changes such as cerebral infarct volume, cerebral edema, and cell apoptosis. A rat cytokine array was utilized to identify the potential cytokines that may be responsible for the therapeutic effect of UTMD-mediated BMSC treatment. Optimal UTMD parameters resulted in an increase in blood-brain barrier (BBB) permeability after 30 min, which returned to baseline 72 h later without causing any residual injury. UTMD application significantly increased the homing of intravenously delivered BMSC, resulting in a 2.2-fold increase in GFP-BMSC cell count on day 3 and a 2.6-fold increase on day 7 compared with intravenous delivery alone. This effect persisted for up to 6 weeks after injection. Intravenous BMSC delivery significantly reduced the volume of cerebral infarct and decreased cerebral edema, leading to a lower Longa score. Furthermore, this effect was further enhanced by UTMD. Acute cerebral infarction induced by MCAO led to elevated matrix metalloproteinase 8 (MMP8) levels in the cerebrospinal fluid, which were significantly reduced following UTMD-mediated BMSC treatment. U ltrasound-targeted microbubble destruction facilitates the migration and homing of BMSC into the brain, possibly by transiently increasing blood-brain barrier (BBB) permeability, thereby improving therapeutic outcomes in an ACI rat model. The observed effect may be partly attributed to modulation of MMP8 levels. Advances in knowledge: UTMD-mediated intravenously delivered BMSC transplantation led to a significant increase in cell homing and reduction of MMP8 levels, resulting in increased therapeutic effect in an acute ischemic cerebral infarction model., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
- Published
- 2024
- Full Text
- View/download PDF
29. Endoscopic endonasal surgery for prolactinomas: prognostic factors for disease control and management of persistent disease.
- Author
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Kalyvas A, Almeida JP, Nassiri F, Lau R, O'Halloran PJ, Mohan N, Wälchli T, Ye VC, Tang DM, Soni P, Potter T, Ezzat S, Kshettry VR, Zadeh G, Recinos PF, and Gentili F
- Subjects
- Humans, Female, Prognosis, Treatment Outcome, Retrospective Studies, Prolactinoma surgery, Prolactinoma pathology, Pituitary Neoplasms surgery, Pituitary Neoplasms pathology
- Abstract
Only a limited number of studies have focused on the results of the Endoscopic Endonasal Approach (EEA) for treatment of prolactinomas. We sought to assess the effectiveness of EEA for prolactinoma surgery, identify factors for disease remission, and present our approach for the management of persistent disease. Forty-seven prolactinomas operated over 10 years, with a mean follow-up of 59.9 months, were included. The primary endpoints were early disease remission and remission at last follow-up. Resistance/intolerance to DA were surgical indications in 76.7%. Disease remission was achieved in 80% of microprolactinomas and 100% of microprolactinomas enclosed by the pituitary. Early disease remission was correlated with female gender (p=0.03), lower preoperative PRL levels (p=0.014), microadenoma (p=0.001), lack of radiological hemorrhage (p=0.001), absence of cavernous sinus (CS) invasion (p<0.001), and extent of resection (EOR) (p<0.001). Persistent disease was reported in 48.9% of patients, with 47% of them achieving remission at last follow-up with DA therapy alone. Repeat EEA and/or radiotherapy were utilized in 6 patients, with 66.7% achieving remission. Last follow-up remission was achieved in 76.6%, with symptomatic improvement in 95.8%. Factors predicting last follow-up remission were no previous operation (p=0.001), absence of CS invasion (p=0.01), and EOR (p<0.001). Surgery is effective for disease control in microprolactinomas. In giant and invasive tumors, it may significantly reduce the tumor volume. A multidisciplinary approach may lead to long-term disease control in three-quarters of patients, with symptomatic improvement in an even greater proportion., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
- Published
- 2023
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30. Decreased eukaryotic initiation factors expression upon temozolomide treatment-potential novel implications for eIFs in glioma therapy.
- Author
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Krassnig S, Leber SL, Orthmann A, Golob-Schwarzl N, Huber HJ, Wohlrab C, Skofler C, Pennauer M, Raicht A, Birkl-Toeglhofer AM, Naumann M, Mahdy-Ali K, von Campe G, Leoni M, Alcaniz J, Hoffmann J, Wälchli T, Weis S, Benesch M, and Haybaeck J
- Subjects
- Humans, Temozolomide therapeutic use, Temozolomide pharmacology, Proto-Oncogene Proteins c-akt metabolism, Phosphatidylinositol 3-Kinases metabolism, Dacarbazine therapeutic use, Dacarbazine pharmacology, Cell Line, Tumor, TOR Serine-Threonine Kinases metabolism, Brain Neoplasms genetics, Glioma drug therapy, Glioma pathology, Glioblastoma drug therapy, Glioblastoma pathology
- Abstract
Purpose: Since glioma therapy is currently still limited until today, new treatment options for this heterogeneous group of tumours are of great interest. Eukaryotic initiation factors (eIFs) are altered in various cancer entities, including gliomas. The purpose of our study was to evaluate the potential of eIFs as novel targets in glioma treatment., Methods: We evaluated eIF protein expression and regulation in 22 glioblastoma patient-derived xenografts (GBM PDX) after treatment with established cytostatics and with regards to mutation profile analyses of GBM PDX., Results: We observed decreased expression of several eIFs upon temozolomide (TMZ) treatment independent from the phosphatidylinositol 3-kinase (PI3K)/ AKT/ mammalian target of the rapamycin (mTOR) signalling pathway. These effects of TMZ treatment were not present in TMZ-resistant PDX. Combination therapy of regorafenib and TMZ re- established the eIF/AKT/mTOR axis., Conclusion: Our study provides novel insights into chemotherapeutic effects on eIF regulation in gliomas and suggests that eIFs are interesting candidates for future research to improve glioma therapy., (© 2023. The Author(s).)
- Published
- 2023
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31. Shaping the brain vasculature in development and disease in the single-cell era.
- Author
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Wälchli T, Bisschop J, Carmeliet P, Zadeh G, Monnier PP, De Bock K, and Radovanovic I
- Subjects
- Humans, Neovascularization, Physiologic physiology, Brain, Signal Transduction, Brain Neoplasms, Central Nervous System Vascular Malformations
- Abstract
The CNS critically relies on the formation and proper function of its vasculature during development, adult homeostasis and disease. Angiogenesis - the formation of new blood vessels - is highly active during brain development, enters almost complete quiescence in the healthy adult brain and is reactivated in vascular-dependent brain pathologies such as brain vascular malformations and brain tumours. Despite major advances in the understanding of the cellular and molecular mechanisms driving angiogenesis in peripheral tissues, developmental signalling pathways orchestrating angiogenic processes in the healthy and the diseased CNS remain incompletely understood. Molecular signalling pathways of the 'neurovascular link' defining common mechanisms of nerve and vessel wiring have emerged as crucial regulators of peripheral vascular growth, but their relevance for angiogenesis in brain development and disease remains largely unexplored. Here we review the current knowledge of general and CNS-specific mechanisms of angiogenesis during brain development and in brain vascular malformations and brain tumours, including how key molecular signalling pathways are reactivated in vascular-dependent diseases. We also discuss how these topics can be studied in the single-cell multi-omics era., (© 2023. Springer Nature Limited.)
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- 2023
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32. Nucleolin promotes angiogenesis and endothelial metabolism along the oncofetal axis in the human brain vasculature.
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Schwab M, de Trizio I, Ghobrial M, Shiu JY, Sürücü O, Girolamo F, Errede M, Yilmaz M, Haybaeck J, Moiraghi A, Monnier PP, Lawler SE, Greenfield JP, Radovanovic I, Frei K, Schlapbach R, Vogel V, Virgintino D, De Bock K, and Wälchli T
- Subjects
- Adult, Humans, Phosphoproteins metabolism, Brain metabolism, Nucleolin, Glioma metabolism, Brain Neoplasms pathology
- Abstract
Glioblastomas are among the deadliest human cancers and are highly vascularized. Angiogenesis is dynamic during brain development, almost quiescent in the adult brain but reactivated in vascular-dependent CNS pathologies, including brain tumors. The oncofetal axis describes the reactivation of fetal programs in tumors, but its relevance in endothelial and perivascular cells of the human brain vasculature in glial brain tumors is unexplored. Nucleolin is a regulator of cell proliferation and angiogenesis, but its roles in the brain vasculature remain unknown. Here, we studied the expression of Nucleolin in the neurovascular unit in human fetal brains, adult brains, and human gliomas in vivo as well as its effects on sprouting angiogenesis and endothelial metabolism in vitro. Nucleolin is highly expressed in endothelial and perivascular cells during brain development, downregulated in the adult brain, and upregulated in glioma. Moreover, Nucleolin expression correlated with glioma malignancy in vivo. In culture, siRNA-mediated Nucleolin knockdown reduced human brain endothelial cell (HCMEC) and HUVEC sprouting angiogenesis, proliferation, filopodia extension, and glucose metabolism. Furthermore, inhibition of Nucleolin with the aptamer AS1411 decreased brain endothelial cell proliferation in vitro. Mechanistically, Nucleolin knockdown in HCMECs and HUVECs uncovered regulation of angiogenesis involving VEGFR2 and of endothelial glycolysis. These findings identify Nucleolin as a neurodevelopmental factor reactivated in glioma that promotes sprouting angiogenesis and endothelial metabolism, characterizing Nucleolin as an oncofetal protein. Our findings have potential implications in the therapeutic targeting of glioma.
- Published
- 2023
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33. The Dyslexia-associated gene KIAA0319L is involved in neuronal migration in the developing chick visual system.
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Charish J, Harada H, Chen X, Wälchli T, Barr CL, and Monnier PP
- Subjects
- Chick Embryo, Mice, Animals, Rats, Neurons physiology, Neurogenesis physiology, Mice, Knockout, Dyslexia genetics
- Abstract
The gene KIAA0319-Like (KIAA0319L) is thought to confer susceptibility for developmental dyslexia. Dyslexia may be caused by alterations in neuronal migration, and in utero knockdown of KIAA0319L in rats indicated migration errors. However, studies carried out with KIAA0319L knockout mice did not reveal an altered neuronal migration phenotype. Gene knockout may activate compensatory mechanisms to buffer against genetic mutations during development. Here we assessed the role of KIAA0319L on migrating neurons in the chick developing tectum. Whole mount in situ hybridization was performed for KIAA0319L on embryonic day (E)3 - E5 chick embryos and in situ hybridization on sections was performed at later stages. The specificity and efficiency of engineered microRNA (miRNA) constructs targeting KIAA0319L for knocking down KIAA0319L were verified. miRNAs were electroporated into E5 chick optic tecta. Our studies demonstrate that KIAA0319L is expressed in the developing chick visual system, as well as in the otic vesicles. Knockdown of KIAA0319L in the optic tectum results in abnormal neuronal migration, strengthening the argument that KIAA0319L is involved in this developmental process.
- Published
- 2023
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- View/download PDF
34. Molecular and genetic mechanisms in brain arteriovenous malformations: new insights and future perspectives.
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Vetiska S, Wälchli T, Radovanovic I, and Berhouma M
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- Humans, Brain pathology, Intracranial Hemorrhages etiology, Cerebral Arteries, Intracranial Arteriovenous Malformations genetics, Intracranial Arteriovenous Malformations surgery
- Abstract
Brain arteriovenous malformations (bAVMs) are rare vascular lesions made of shunts between cerebral arteries and veins without the interposition of a capillary bed. The majority of bAVMs are asymptomatic, but some may be revealed by seizures and potentially life-threatening brain hemorrhage. The management of unruptured bAVMs remains a matter of debate. Significant progress in the understanding of their pathogenesis has been made during the last decade, particularly using genome sequencing and biomolecular analysis. Herein, we comprehensively review the recent molecular and genetic advances in the study of bAVMs that not only allow a better understanding of the genesis and growth of bAVMs, but also open new insights in medical treatment perspectives., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
- Published
- 2022
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35. Endovascular Management of Intracranial Dural AVFs: Transvenous Approach.
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Bhatia KD, Lee H, Kortman H, Klostranec J, Guest W, Wälchli T, Radovanovic I, Krings T, and Pereira VM
- Subjects
- Humans, Cavernous Sinus, Central Nervous System Vascular Malformations diagnostic imaging, Central Nervous System Vascular Malformations surgery, Cerebral Veins diagnostic imaging, Cerebral Veins surgery, Embolization, Therapeutic, Endovascular Procedures
- Abstract
In this third review article on the endovascular management of intracranial dural AVFs, we discuss transvenous embolization approaches. Transvenous embolization is increasingly popular and now the first-line approach for ventral dural AVFs involving the cavernous sinus and hypoglossal canal. In addition, transvenous embolization is increasingly used in lateral epidural dural AVFs in high-risk locations such as the petrous and ethmoid regions. The advantage of transvenous embolization in these locations is the ability to retrogradely embolize the draining vein and fistula while reducing the risk of ischemic cranial neuropathy or brain parenchymal infarction commonly feared from a transarterial approach. By means of coils ± ethylene-vinyl alcohol copolymer, transvenous embolization can achieve angiographic cure rates of 80%-90% in ventral locations. Potential complications include transient cranial neuropathy, neurologic deterioration due to venous outflow obstruction, and perforation while navigating pial veins. Transvenous embolization should be considered when dural AVFs arise in proximity to the vasa nervosum or extracranial-intracranial anastomoses., (© 2022 by American Journal of Neuroradiology.)
- Published
- 2022
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36. Endovascular Management of Intracranial Dural Arteriovenous Fistulas: Transarterial Approach.
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Bhatia KD, Lee H, Kortman H, Klostranec J, Guest W, Wälchli T, Radovanovic I, Krings T, and Pereira VM
- Subjects
- Cerebral Angiography, Cranial Sinuses, Humans, Treatment Outcome, Central Nervous System Vascular Malformations diagnostic imaging, Central Nervous System Vascular Malformations surgery, Embolization, Therapeutic, Endovascular Procedures, Transverse Sinuses
- Abstract
In this second of 3 review articles on the endovascular management of intracranial dural AVFs, we discuss transarterial treatment approaches. The treatment goal is to occlude the fistulous point, including the most distal portion of the arterial supply together with the most proximal portion of the draining vein (ie, the "foot" of the vein), which can be accomplished with liquid embolic agents via transarterial access. Anatomic factors to consider when assessing the safety and efficacy of a transarterial approach using liquid embolic agents include location, angioarchitecture, and proximity of arterial feeders to both the vasa nervosum of adjacent cranial nerves and the external carotid-internal carotid/vertebral artery anastomoses. Anatomic locations typically favorable for transarterial approaches include but are not limited to the transverse/sigmoid sinus, cerebral convexity, and superior sagittal sinus. In this review article, we discuss the technical approaches, outcomes, potential complications, and complication avoidance strategies for transarterial embolization., (© 2022 by American Journal of Neuroradiology.)
- Published
- 2022
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37. MicroRNA-Based Regulation of Embryonic Endothelial Cell Heterogeneity at Single-Cell Resolution.
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Wälchli T, Farnhammer F, and Fish JE
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- Embryonic Stem Cells, Endothelial Cells, MicroRNAs genetics
- Published
- 2022
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38. Endovascular Management of Intracranial Dural AVFs: Principles.
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Bhatia KD, Lee H, Kortman H, Klostranec J, Guest W, Wälchli T, Radovanovic I, Krings T, and Pereira VM
- Subjects
- Cerebral Angiography, Drainage, Dura Mater blood supply, Dura Mater diagnostic imaging, Dura Mater surgery, Humans, Veins, Central Nervous System Vascular Malformations diagnostic imaging, Central Nervous System Vascular Malformations surgery, Embolization, Therapeutic, Endovascular Procedures
- Abstract
Intracranial dural AVFs are abnormal communications between arteries that supply the dura mater and draining cortical veins or venous sinuses. They are believed to form as a response to venous insults such as thrombosis, trauma, or infection. Classification and management are dependent on the presence of drainage/reflux into cortical veins because such drainage markedly elevates the risk of hemorrhage or venous congestion, resulting in neurologic deficits. AVFs with tolerable symptoms and benign drainage patterns can be managed conservatively. Intolerable symptoms, presentation with hemorrhage/neurologic deficits, or aggressive drainage patterns are indications for intervention. Treatment options include microsurgical disconnection, endovascular transarterial embolization, transvenous embolization, or a combination. This is the first in a series of 3 articles on endovascular management of intracranial dural AVFs, in which we outline the principles and outcomes of endovascular treatment., (© 2022 by American Journal of Neuroradiology.)
- Published
- 2022
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39. In Reply to the Letter to the Editor Regarding 'Symptomatic Unruptured Arteriovenous Malformations: Focal Oedema, Thrombosis and Vessel Wall Enhancement. A Retrospective Cohort Study'.
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Kortman H, Bhatia KD, Nicholson P, Wälchli T, and Krings T
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- Brain Edema complications, Humans, Image Enhancement, Intracranial Arteriovenous Malformations complications, Magnetic Resonance Imaging, Thrombosis complications, Intracranial Arteriovenous Malformations diagnostic imaging, Intracranial Arteriovenous Malformations pathology
- Published
- 2021
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40. Hierarchical imaging and computational analysis of three-dimensional vascular network architecture in the entire postnatal and adult mouse brain.
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Wälchli T, Bisschop J, Miettinen A, Ulmann-Schuler A, Hintermüller C, Meyer EP, Krucker T, Wälchli R, Monnier PP, Carmeliet P, Vogel J, and Stampanoni M
- Subjects
- Animals, Mice, Microscopy, Electron, Scanning methods, Corrosion Casting methods, Blood Vessels diagnostic imaging, Blood Vessels growth & development, Blood Vessels anatomy & histology, Brain blood supply, Brain diagnostic imaging, Brain growth & development, Imaging, Three-Dimensional methods, X-Ray Microtomography methods
- Abstract
The formation of new blood vessels and the establishment of vascular networks are crucial during brain development, in the adult healthy brain, as well as in various diseases of the central nervous system. Here, we describe a step-by-step protocol for our recently developed method that enables hierarchical imaging and computational analysis of vascular networks in postnatal and adult mouse brains. The different stages of the procedure include resin-based vascular corrosion casting, scanning electron microscopy, synchrotron radiation and desktop microcomputed tomography imaging, and computational network analysis. Combining these methods enables detailed visualization and quantification of the 3D brain vasculature. Network features such as vascular volume fraction, branch point density, vessel diameter, length, tortuosity and directionality as well as extravascular distance can be obtained at any developmental stage from the early postnatal to the adult brain. This approach can be used to provide a detailed morphological atlas of the entire mouse brain vasculature at both the postnatal and the adult stage of development. Our protocol allows the characterization of brain vascular networks separately for capillaries and noncapillaries. The entire protocol, from mouse perfusion to vessel network analysis, takes ~10 d., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)
- Published
- 2021
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41. Symptomatic Unruptured Arteriovenous Malformations: Focal Edema, Thrombosis, and Vessel Wall Enhancement: A Retrospective Cohort Study.
- Author
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Kortman H, Bhatia KD, Wälchli T, Nicholson P, and Krings T
- Subjects
- Aged, Angiography, Digital Subtraction, Brain pathology, Brain Edema etiology, Brain Edema surgery, Cerebrovascular Circulation, Cohort Studies, Endovascular Procedures methods, Female, Humans, Image Processing, Computer-Assisted, Intracranial Arteriovenous Malformations complications, Intracranial Arteriovenous Malformations surgery, Intracranial Thrombosis etiology, Intracranial Thrombosis surgery, Magnetic Resonance Imaging, Male, Middle Aged, Retrospective Studies, Young Adult, Blood Vessels pathology, Brain Edema therapy, Intracranial Arteriovenous Malformations therapy, Intracranial Thrombosis therapy
- Abstract
Background: Focal brain edema in unruptured brain arteriovenous malformations (AVMs) is rare and associated with venous outflow abnormalities and aneurysm growth. These patients have an increased rate of progressive neurologic symptoms, as well as a potentially increased risk of hemorrhage. In this study, we aim to assess in further detail the relationship between perifocal edema and enhancement of the vessel wall in symptomatic patients with an unruptured brain AVM., Methods: A single-center retrospective cohort study of all patients presenting with an unruptured AVM at Toronto Western Hospital from 2009 to 2019 was performed. Patients were included for review if they had focal edema surrounding an AVM on magnetic resonance imaging (MRI) and a contrast-enhanced MRI scan. Associated digital subtraction angiography studies were reviewed., Results: A total of 122 patients presented with an unruptured AVM. Twelve symptomatic patients presented with focal edema surrounding the AVM. Six patients had focal edema and contrast-enhanced MRI performed. All 6 demonstrated luminal thrombosis at the level of the brain edema on MRI. Moreover, the vessel wall demonstrated enhancement at the level of the luminal thrombus in all., Conclusions: Vessel wall enhancement, perifocal edema, and luminal thrombosis demonstrated in all patients with unruptured AVM points towards a common mechanism. We suspect an interplay between vascular hypoxia, the innate immune system, and thrombosis formation. Current research in the field of immunothrombosis supports this theory. Unravelling the mechanisms involved is important because it might guide therapy for patients with an unruptured AVM towards noninvasive options., (Crown Copyright © 2021. Published by Elsevier Inc. All rights reserved.)
- Published
- 2021
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42. Cholesterol synthesis inhibition promotes axonal regeneration in the injured central nervous system.
- Author
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Shabanzadeh AP, Charish J, Tassew NG, Farhani N, Feng J, Qin X, Sugita S, Mothe AJ, Wälchli T, Koeberle PD, and Monnier PP
- Subjects
- Animals, Anticholesteremic Agents pharmacology, Axons drug effects, Axons pathology, Cell Survival, Chick Embryo, Membrane Microdomains drug effects, Membrane Microdomains metabolism, Membrane Proteins drug effects, Membrane Proteins metabolism, Myelin Sheath, Neurons metabolism, Optic Nerve metabolism, Optic Nerve pathology, Optic Nerve Injuries metabolism, Optic Nerve Injuries pathology, Photoreceptor Cells, Prenylation, Prodrugs, Rats, Retina, Retinitis Pigmentosa, trans-1,4-Bis(2-chlorobenzaminomethyl)cyclohexane Dihydrochloride pharmacology, Hydroxymethylglutaryl-CoA Reductase Inhibitors pharmacology, Lovastatin pharmacology, Nerve Regeneration drug effects, Neurons drug effects, Optic Nerve drug effects
- Abstract
Neuronal regeneration in the injured central nervous system is hampered by multiple extracellular proteins. These proteins exert their inhibitory action through interactions with receptors that are located in cholesterol rich compartments of the membrane termed lipid rafts. Here we show that cholesterol-synthesis inhibition prevents the association of the Neogenin receptor with lipid rafts. Furthermore, we show that cholesterol-synthesis inhibition enhances axonal growth both on inhibitory -myelin and -RGMa substrates. Following optic nerve injury, lowering cholesterol synthesis with both drugs and siRNA-strategies allows for robust axonal regeneration and promotes neuronal survival. Cholesterol inhibition also enhanced photoreceptor survival in a model of Retinitis Pigmentosa. Our data reveal that Lovastatin leads to several opposing effects on regenerating axons: cholesterol synthesis inhibition promotes regeneration whereas altered prenylation impairs regeneration. We also show that the lactone prodrug form of lovastatin has differing effects on regeneration when compared to the ring-open hydroxy-acid form. Thus the association of cell surface receptors with lipid rafts contributes to axonal regeneration inhibition, and blocking cholesterol synthesis provides a potential therapeutic approach to promote neuronal regeneration and survival in the diseased Central Nervous System. SIGNIFICANCE STATEMENT: Statins have been intensively used to treat high levels of cholesterol in humans. However, the effect of cholesterol inhibition in both the healthy and the diseased brain remains controversial. In particular, it is unclear whether cholesterol inhibition with statins can promote regeneration and survival following injuries. Here we show that late stage cholesterol inhibition promotes robust axonal regeneration following optic nerve injury. We identified distinct mechanisms of action for activated vs non-activated Lovastatin that may account for discrepancies found in the literature. We show that late stage cholesterol synthesis inhibition alters Neogenin association with lipid rafts, thereby i) neutralizing the inhibitory function of its ligand and ii) offering a novel opportunity to promote CNS regeneration and survival following injuries., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Published
- 2021
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43. CGRP Receptor Antagonism in COVID-19: Potential Cardiopulmonary Adverse Effects.
- Author
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Skaria T, Wälchli T, and Vogel J
- Subjects
- Animals, Humans, COVID-19 metabolism, COVID-19 pathology, Calcitonin Gene-Related Peptide Receptor Antagonists adverse effects, Calcitonin Gene-Related Peptide Receptor Antagonists therapeutic use, Heart Diseases chemically induced, Heart Diseases metabolism, Heart Diseases pathology, Receptors, Calcitonin Gene-Related Peptide metabolism, SARS-CoV-2 metabolism, COVID-19 Drug Treatment
- Abstract
Recently, the US FDA has authorized a drug repurposing trial with calcitonin gene-related peptide (CGRP) receptor antagonists to reduce lung inflammation in coronavirus 2019 (COVID-19). However, the well-established cardiopulmonary protective effects of CGRP raise concerns about the safety of antagonizing CGRP in COVID-19. Awareness regarding potential cardiopulmonary adverse effects may enable their early detection and prevent illness from worsening., (Copyright © 2020 Elsevier Ltd. All rights reserved.)
- Published
- 2021
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44. Role of the GLUT1 Glucose Transporter in Postnatal CNS Angiogenesis and Blood-Brain Barrier Integrity.
- Author
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Veys K, Fan Z, Ghobrial M, Bouché A, García-Caballero M, Vriens K, Conchinha NV, Seuwen A, Schlegel F, Gorski T, Crabbé M, Gilardoni P, Ardicoglu R, Schaffenrath J, Casteels C, De Smet G, Smolders I, Van Laere K, Abel ED, Fendt SM, Schroeter A, Kalucka J, Cantelmo AR, Wälchli T, Keller A, Carmeliet P, and De Bock K
- Subjects
- AMP-Activated Protein Kinases metabolism, Animals, Brain cytology, Cell Movement, Cell Proliferation, Endothelial Cells physiology, Endothelium, Endothelium, Vascular physiology, Energy Metabolism, Glucose metabolism, Glucose Transporter Type 1 antagonists & inhibitors, Glycolysis, Humans, Mice, Retina cytology, Blood-Brain Barrier physiology, Brain blood supply, Endothelial Cells metabolism, Glucose Transporter Type 1 physiology, Neovascularization, Physiologic, Retinal Vessels
- Abstract
Rationale: Endothelial cells (ECs) are highly glycolytic and generate the majority of their energy via the breakdown of glucose to lactate. At the same time, a main role of ECs is to allow the transport of glucose to the surrounding tissues. GLUT1 (glucose transporter isoform 1/ Slc2a1 ) is highly expressed in ECs of the central nervous system (CNS) and is often implicated in blood-brain barrier (BBB) dysfunction, but whether and how GLUT1 controls EC metabolism and function is poorly understood., Objective: We evaluated the role of GLUT1 in endothelial metabolism and function during postnatal CNS development as well as at the adult BBB., Methods and Results: Inhibition of GLUT1 decreases EC glucose uptake and glycolysis, leading to energy depletion and the activation of the cellular energy sensor AMPK (AMP-activated protein kinase), and decreases EC proliferation without affecting migration. Deletion of GLUT1 from the developing postnatal retinal endothelium reduces retinal EC proliferation and lowers vascular outgrowth, without affecting the number of tip cells. In contrast, in the brain, we observed a lower number of tip cells in addition to reduced brain EC proliferation, indicating that within the CNS, organotypic differences in EC metabolism exist. Interestingly, when ECs become quiescent, endothelial glycolysis is repressed, and GLUT1 expression increases in a Notch-dependent fashion. GLUT1 deletion from quiescent adult ECs leads to severe seizures, accompanied by neuronal loss and CNS inflammation. Strikingly, this does not coincide with BBB leakiness, altered expression of genes crucial for BBB barrier functioning nor reduced vascular function. Instead, we found a selective activation of inflammatory and extracellular matrix related gene sets., Conclusions: GLUT1 is the main glucose transporter in ECs and becomes uncoupled from glycolysis during quiescence in a Notch-dependent manner. It is crucial for developmental CNS angiogenesis and adult CNS homeostasis but does not affect BBB barrier function.
- Published
- 2020
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45. Navigated Intraoperative 2-Dimensional Ultrasound in High-Grade Glioma Surgery: Impact on Extent of Resection and Patient Outcome.
- Author
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Moiraghi A, Prada F, Delaidelli A, Guatta R, May A, Bartoli A, Saini M, Perin A, Wälchli T, Momjian S, Bijlenga P, Schaller K, and DiMeco F
- Subjects
- Humans, Neuronavigation, Retrospective Studies, Ultrasonography, Brain Neoplasms diagnostic imaging, Brain Neoplasms surgery, Glioma diagnostic imaging, Glioma surgery
- Abstract
Background: Maximizing extent of resection (EOR) and reducing residual tumor volume (RTV) while preserving neurological functions is the main goal in the surgical treatment of gliomas. Navigated intraoperative ultrasound (N-ioUS) combining the advantages of ultrasound and conventional neuronavigation (NN) allows for overcoming the limitations of the latter., Objective: To evaluate the impact of real-time NN combining ioUS and preoperative magnetic resonance imaging (MRI) on maximizing EOR in glioma surgery compared to standard NN., Methods: We retrospectively reviewed a series of 60 cases operated on for supratentorial gliomas: 31 operated under the guidance of N-ioUS and 29 resected with standard NN. Age, location of the tumor, pre- and postoperative Karnofsky Performance Status (KPS), EOR, RTV, and, if any, postoperative complications were evaluated., Results: The rate of gross total resection (GTR) in NN group was 44.8% vs 61.2% in N-ioUS group. The rate of RTV > 1 cm3 for glioblastomas was significantly lower for the N-ioUS group (P < .01). In 13/31 (42%), RTV was detected at the end of surgery with N-ioUS. In 8 of 13 cases, (25.8% of the cohort) surgeons continued with the operation until complete resection. Specificity was greater in N-ioUS (42% vs 31%) and negative predictive value (73% vs 54%). At discharge, the difference between pre- and postoperative KPS was significantly higher for the N-ioUS (P < .01)., Conclusion: The use of an N-ioUS-based real-time has been beneficial for resection in noneloquent high-grade glioma in terms of both EOR and neurological outcome, compared to standard NN. N-ioUS has proven usefulness in detecting RTV > 1 cm3., (Copyright © 2019 by the Congress of Neurological Surgeons.)
- Published
- 2020
- Full Text
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46. Artery of Davidoff and Schechter Supply in Dural Arteriovenous Fistulas.
- Author
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Bhatia KD, Kortman H, Wälchli T, Radovanovic I, Pereira VM, and Krings T
- Subjects
- Aged, Angiography, Digital Subtraction methods, Cerebral Angiography, Embolization, Therapeutic methods, Endovascular Procedures methods, Female, Humans, Male, Middle Aged, Retrospective Studies, Central Nervous System Vascular Malformations therapy, Dura Mater blood supply, Meningeal Arteries diagnostic imaging
- Abstract
The artery of Davidoff and Schechter is a dural branch of the posterior cerebral artery that can supply the meninges close to the falcotentorial junction. It is usually not identified on angiography except when enlarged in the setting of a dural AVF or meningioma. The impact on treatment of the artery of Davidoff and Schechter supply to a fistula is not well-described in the literature. Our retrospective analysis of patients with dural AVFs treated at the Toronto Western Hospital between 2006 and 2018 identified 6 patients with dural AVFs receiving supply from artery of Davidoff and Schechter (of a total of 173 patients with dural AVFs). All patients were initially treated by transarterial embolization using liquid embolic agents. Three patients required a second endovascular procedure partly due to residual supply from artery of Davidoff and Schechter, and in all cases, angiographic cure was obtained. The treatment approach, challenges encountered, and potential complications of treating such fistulas are described., (© 2020 by American Journal of Neuroradiology.)
- Published
- 2020
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47. Blood Pressure Normalization-Independent Cardioprotective Effects of Endogenous, Physical Activity-Induced αCGRP (α Calcitonin Gene-Related Peptide) in Chronically Hypertensive Mice.
- Author
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Skaria T, Mitchell KJ, Vogel O, Wälchli T, Gassmann M, and Vogel J
- Subjects
- Animals, Biomarkers blood, Cells, Cultured, Chronic Disease, Hypertension prevention & control, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Treatment Outcome, Blood Pressure physiology, Calcitonin Gene-Related Peptide blood, Hypertension blood, Hypertension therapy, Physical Conditioning, Animal methods, Physical Conditioning, Animal physiology
- Abstract
Rationale: αCGRP (α calcitonin gene-related peptide), one of the strongest vasodilators, is cardioprotective in hypertension by reducing the elevated blood pressure., Objective: However, we hypothesize that endogenous, physical activity-induced αCGRP has blood pressure-independent cardioprotective effects in chronic hypertension., Methods and Results: Chronically hypertensive (one-kidney-one-clip surgery) wild-type and αCGRP
-/- sedentary or voluntary wheel running mice were treated with vehicle, αCGRP, or the αCGRP receptor antagonist CGRP8-37. Cardiac function and myocardial phenotype were evaluated echocardiographically and by molecular, cellular, and histological analysis, respectively. Blood pressure was similar among all hypertensive experimental groups. Endogenous αCGRP limited pathological remodeling and heart failure in sedentary, chronically hypertensive wild-type mice. In these mice, voluntary wheel running significantly improved myocardial phenotype and function, which was abolished by CGRP8-37 treatment. In αCGRP-/- mice, αCGRP treatment, in contrast to voluntary wheel running, improved myocardial phenotype and function. Specific inhibition of proliferation and myofibroblast differentiation of primary, murine cardiac fibroblasts by αCGRP suggests involvement of these cells in αCGRP-dependent blunting of pathological cardiac remodeling., Conclusions: Endogenous, physical activity-induced αCGRP has blood pressure-independent cardioprotective effects and is crucial for maintaining cardiac function in chronic hypertension. Consequently, inhibiting endogenous αCGRP signaling, as currently approved for migraine prophylaxis, could endanger patients with hypertension.- Published
- 2019
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48. Efficacy of intraoperative epidural triamcinolone application in lumbar microdiscectomy: a matched-control study.
- Author
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Stienen MN, Joswig H, Chau I, Neidert MC, Bellut D, Wälchli T, Schaller K, and Gautschi OP
- Subjects
- Adult, Aged, Female, Humans, Male, Middle Aged, Pain surgery, Quality of Life, Retrospective Studies, Treatment Outcome, Young Adult, Intervertebral Disc Degeneration therapy, Lumbar Vertebrae surgery, Pain Management, Triamcinolone therapeutic use
- Abstract
OBJECTIVE The purpose of this study was to investigate whether the intraoperative application of an epidural steroid (ES) on the decompressed nerve root improves short- and midterm subjective and objective clinical outcomes after lumbar microdiscectomy. METHODS This study was a retrospective analysis of a 2-center database including consecutive cases in which patients underwent lumbar microdiscectomy. All patients who received ES application (40 mg triamcinolone, ES group) were matched by age and sex to patients who had not received ES application (control group). Objective functional impairment (OFI) was determined using age- and sex-adjusted T-scores of the Timed Up and Go (TUG) test. Back and leg pain (visual analog scale), functional impairment (Oswestry Disability Index [ODI], Roland-Morris Disability Index [RMDI], and health-related quality of life (hrQoL; 12-Item Short Form Health Survey [SF-12] physical component summary [PSC] score and EuroQol [EQ-5D index]) were measured at baseline, on postoperative day 3, and at postoperative week 6. RESULTS Fifty-three patients who received ES application were matched with 101 controls. There were no baseline demographic or disease-specific differences between the study groups, and preoperative pain, functional impairment, and hrQoL were similar. On postoperative day 3, the ES group had less disability on the RMDI (mean 7.4 vs 10.3, p = 0.003) and higher hrQoL as determined by the SF-12 PCS (36.5 vs 32.7, p = 0.004). At week 6, the ES group had less disability on the RMDI (3.6 vs 5.7, p = 0.050) and on the ODI by trend (17.0 vs 24.4, p = 0.056); better hrQoL, determined by the SF-12 PCS (44.3 vs 39.9, p = 0.018); and lower OFI (TUG test T-score 100.5 vs 110.2, p = 0.005). The week 6 responder status based on the minimum clinically important difference (MCID) was similar in the ES and control groups for each metric. The rates and severity of complications were similar, with a 3.8% and 4.0% reoperation rate in the ES group and control group, respectively (p = 0.272). There was a tendency for shorter hospitalization in the ES group (5.0 vs 5.8 days, p = 0.066). CONCLUSIONS Intraoperative ES application on the decompressed nerve root is an effective adjunct treatment that may lower subjective and objective functional impairment and increase hrQoL in the short and intermediate term after lumbar microdiscectomy. However, group differences were lower than the commonly accepted MCIDs for each metric, indicating that the effect size of the benefit is limited. ■ CLASSIFICATION OF EVIDENCE Type of question: therapeutic; study design: retrospective cohort trial; evidence: Class II.
- Published
- 2018
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49. Reliable? The Value of Early Postoperative Magnetic Resonance Imaging after Cerebral Cavernous Malformation Surgery.
- Author
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Chen B, Göricke S, Wrede K, Jabbarli R, Wälchli T, Jägersberg M, Sure U, and Dammann P
- Subjects
- Adolescent, Adult, Aged, Brain Neoplasms complications, Brain Neoplasms metabolism, Brain Neoplasms surgery, Child, Child, Preschool, Cohort Studies, Epilepsy, Female, Hemangioma, Cavernous, Central Nervous System complications, Hemangioma, Cavernous, Central Nervous System metabolism, Hemangioma, Cavernous, Central Nervous System surgery, Hemosiderin metabolism, Humans, Male, Middle Aged, Neoplasm, Residual, Predictive Value of Tests, Prospective Studies, Reproducibility of Results, Sensitivity and Specificity, Young Adult, Brain Neoplasms diagnostic imaging, Hemangioma, Cavernous, Central Nervous System diagnostic imaging, Magnetic Resonance Imaging methods, Postoperative Period
- Abstract
Background: Cerebral cavernous malformations (CCM) can cause intracerebral hemorrhage. The lesions themselves are frequently associated with perifocal hemosiderin deposits caused by repetitive microhemorrhages. Main indications for a surgical treatment are recurrent symptomatic hemorrhages or cavernoma-related epilepsy. After surgical resection, follow-up magnetic resonance imaging (MRI) is usually performed to confirm 1) the complete resection of the CCM and, especially in cases of cavernoma-related epilepsy, 2) the complete resection of the hemosiderin deposits., Methods: This prospective study evaluates the value of early postoperative MRI (within 72 hours) regarding the detection of CCM or hemosiderin remnants compared with a standard 3-6 months postoperative MRI control in 61 CCM cases., Results: Sensitivity of early postoperative MRI for CCM remnant detection was 66.67% (95% confidence interval [CI], 9.43%-99.16%), specificity was 76.74% (95% CI, 61.37%-88.24%), positive predictive value was 16.67% (95% CI, 2.09%-48.41%), and negative predictive value was 97.06% (95% CI, 84.67%-99.93%). Because of the high number of patients who could not be evaluated because of imaging artifacts, sensitivity and specificity analysis was not performed for early postoperative MRI using T2*/susceptibility-weighted imaging to assess hemosiderin remnants. Sensitivity of early postoperative MRI for hemosiderin remnant detection using T2-weighted sequences was 85.71% (95% CI, 63.66%-96.95%), specificity was 66.67% (95% CI, 44.68%-84.37%), positive predictive value was 69.23% (95% CI, 55.45%-80.27%), and negative predictive value was 84.21% (95% CI, 64.31%-94.04%)., Conclusions: Our data suggest that early postoperative MRI after CCM surgery is often hampered by imaging artifacts creating false-positive results and therefore ineligible for a resection control. However, reliability of a negative result on early postoperative T2-weighted MRI is relatively high regarding both CCM and hemosiderin remnants., (Copyright © 2017 Elsevier Inc. All rights reserved.)
- Published
- 2017
- Full Text
- View/download PDF
50. Nogo-A regulates vascular network architecture in the postnatal brain.
- Author
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Wälchli T, Ulmann-Schuler A, Hintermüller C, Meyer E, Stampanoni M, Carmeliet P, Emmert MY, Bozinov O, Regli L, Schwab ME, Vogel J, and Hoerstrup SP
- Subjects
- Animals, Central Nervous System blood supply, Cerebral Cortex blood supply, Gene Deletion, Imaging, Three-Dimensional methods, Mice, Nogo Proteins genetics, Central Nervous System growth & development, Neovascularization, Physiologic, Nogo Proteins physiology
- Abstract
Recently, we discovered a new role for the well-known axonal growth inhibitory molecule Nogo-A as a negative regulator of angiogenesis in the developing central nervous system. However, how Nogo-A affected the three-dimensional (3D) central nervous system (CNS) vascular network architecture remained unknown. Here, using vascular corrosion casting, hierarchical, synchrotron radiation μCT-based network imaging and computer-aided network analysis, we found that genetic ablation of Nogo-A significantly increased the three-dimensional vascular volume fraction in the postnatal day 10 (P10) mouse brain. More detailed analysis of the cerebral cortex revealed that this effect was mainly due to an increased number of capillaries and capillary branchpoints. Interestingly, other vascular parameters such as vessel diameter, -length, -tortuosity, and -volume were comparable between both genotypes for non-capillary vessels and capillaries. Taken together, our three-dimensional data showing more vessel segments and branchpoints at unchanged vessel morphology suggest that stimulated angiogenesis upon Nogo-A gene deletion results in the insertion of complete capillary micro-networks and not just single vessels into existing vascular networks. These findings significantly enhance our understanding of how angiogenesis, vascular remodeling, and three-dimensional vessel network architecture are regulated during central nervous system development. Nogo-A may therefore be a potential novel target for angiogenesis-dependent central nervous system pathologies such as brain tumors or stroke.
- Published
- 2017
- Full Text
- View/download PDF
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