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Research Article

Post-Stroke Inhibition of Induced NADPH Oxidase Type 4 Prevents Oxidative Stress and Neurodegeneration

  • Christoph Kleinschnitz mail,

    h.schmidt@farmaco.unimaas.nl (HHHWS); christoph.kleinschnitz@mail.uni-wuerzburg.de (CK)

    Affiliation: Neurologische Klinik und Poliklinik, Universität Würzburg, Würzburg, Germany

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  • Henrike Grund,

    Affiliation: Rudolf-Buchheim-Institut für Pharmakologie & Medizinische Klinik, Justus-Liebig-Universität, Gießen, Germany

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  • Kirstin Wingler,

    Affiliations: Rudolf-Buchheim-Institut für Pharmakologie & Medizinische Klinik, Justus-Liebig-Universität, Gießen, Germany, Department of Pharmacology and Centre for Vascular Health, Monash University, Melbourne, Australia, Department of Pharmacology and Toxicology and Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, The Netherlands, National Stroke Research Institute, Florey Neuroscience Institutes, Melbourne, Australia

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  • Melanie E. Armitage,

    Affiliations: Department of Pharmacology and Centre for Vascular Health, Monash University, Melbourne, Australia, National Stroke Research Institute, Florey Neuroscience Institutes, Melbourne, Australia

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  • Emma Jones,

    Affiliation: Department of Pharmacology and Centre for Vascular Health, Monash University, Melbourne, Australia

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  • Manish Mittal,

    Affiliation: Rudolf-Buchheim-Institut für Pharmakologie & Medizinische Klinik, Justus-Liebig-Universität, Gießen, Germany

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  • David Barit,

    Affiliation: Baker IDI Heart and Diabetes Institute, Juvenile Diabetes Research Foundation (JDRF) International Center for Diabetic Complications Research, Melbourne, Australia

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  • Tobias Schwarz,

    Affiliation: Neurologische Klinik und Poliklinik, Universität Würzburg, Würzburg, Germany

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  • Christian Geis,

    Affiliation: Neurologische Klinik und Poliklinik, Universität Würzburg, Würzburg, Germany

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  • Peter Kraft,

    Affiliation: Neurologische Klinik und Poliklinik, Universität Würzburg, Würzburg, Germany

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  • Konstanze Barthel,

    Affiliation: Abteilung Neurologie, Georg-August Universität Göttingen, Göttingen, Germany

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  • Michael K. Schuhmann,

    Affiliations: Neurologische Klinik und Poliklinik, Universität Würzburg, Würzburg, Germany, Universitätsklinik Münster, Klinik und Poliklinik für Neurologie—Entzündliche Erkrankungen des Nervensystems und Neuroonkologie, Münster, Germany

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  • Alexander M. Herrmann,

    Affiliations: Neurologische Klinik und Poliklinik, Universität Würzburg, Würzburg, Germany, Universitätsklinik Münster, Klinik und Poliklinik für Neurologie—Entzündliche Erkrankungen des Nervensystems und Neuroonkologie, Münster, Germany

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  • Sven G. Meuth,

    Affiliations: Neurologische Klinik und Poliklinik, Universität Würzburg, Würzburg, Germany, Universitätsklinik Münster, Klinik und Poliklinik für Neurologie—Entzündliche Erkrankungen des Nervensystems und Neuroonkologie, Münster, Germany

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  • Guido Stoll,

    Affiliation: Neurologische Klinik und Poliklinik, Universität Würzburg, Würzburg, Germany

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  • Sabine Meurer,

    Affiliation: Department of Pharmacology and Centre for Vascular Health, Monash University, Melbourne, Australia

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  • Anja Schrewe,

    Affiliation: Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, München, Germany

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  • Lore Becker,

    Affiliations: Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, München, Germany, Friedrich-Baur-Institut an der Neurologischen Klinik, Klinikum der Ludwig-Maximilians-Universität München, München, Germany

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  • Valérie Gailus-Durner,

    Affiliation: Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, München, Germany

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  • Helmut Fuchs,

    Affiliation: Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, München, Germany

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  • Thomas Klopstock,

    Affiliation: Friedrich-Baur-Institut an der Neurologischen Klinik, Klinikum der Ludwig-Maximilians-Universität München, München, Germany

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  • Martin Hrabé de Angelis,

    Affiliations: Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, München, Germany, Lehrstuhl für Experimentelle Genetik, Technische Universität München, Freising-Weihenstephan, Germany

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  • Karin Jandeleit-Dahm,

    Affiliation: Baker IDI Heart and Diabetes Institute, Juvenile Diabetes Research Foundation (JDRF) International Center for Diabetic Complications Research, Melbourne, Australia

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  • Ajay M. Shah,

    Affiliation: King's College London School of Medicine, The James Black Centre, Cardiovascular Division, London, United Kingdom

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  • Norbert Weissmann,

    Affiliation: Rudolf-Buchheim-Institut für Pharmakologie & Medizinische Klinik, Justus-Liebig-Universität, Gießen, Germany

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  • Harald H. H. W. Schmidt mail

    h.schmidt@farmaco.unimaas.nl (HHHWS); christoph.kleinschnitz@mail.uni-wuerzburg.de (CK)

    Affiliations: Rudolf-Buchheim-Institut für Pharmakologie & Medizinische Klinik, Justus-Liebig-Universität, Gießen, Germany, Department of Pharmacology and Centre for Vascular Health, Monash University, Melbourne, Australia, Department of Pharmacology and Toxicology and Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, The Netherlands, National Stroke Research Institute, Florey Neuroscience Institutes, Melbourne, Australia

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  • Published: September 21, 2010
  • DOI: 10.1371/journal.pbio.1000479

About the Authors

Christoph Kleinschnitz, Tobias Schwarz, Christian Geis, Peter Kraft, Michael K. Schuhmann, Alexander M. Herrmann, Sven G. Meuth, Guido Stoll
Neurologische Klinik und Poliklinik, Universität Würzburg, Würzburg, Germany
Henrike Grund, Kirstin Wingler, Manish Mittal, Norbert Weissmann, Harald H. H. W. Schmidt
Rudolf-Buchheim-Institut für Pharmakologie & Medizinische Klinik, Justus-Liebig-Universität, Gießen, Germany
Kirstin Wingler, Melanie E. Armitage, Emma Jones, Sabine Meurer, Harald H. H. W. Schmidt
Department of Pharmacology and Centre for Vascular Health, Monash University, Melbourne, Australia
Kirstin Wingler, Harald H. H. W. Schmidt
Department of Pharmacology and Toxicology and Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, The Netherlands
Kirstin Wingler, Melanie E. Armitage, Harald H. H. W. Schmidt
National Stroke Research Institute, Florey Neuroscience Institutes, Melbourne, Australia
David Barit, Karin Jandeleit-Dahm
Baker IDI Heart and Diabetes Institute, Juvenile Diabetes Research Foundation (JDRF) International Center for Diabetic Complications Research, Melbourne, Australia
Konstanze Barthel
Abteilung Neurologie, Georg-August Universität Göttingen, Göttingen, Germany
Michael K. Schuhmann, Alexander M. Herrmann, Sven G. Meuth
Universitätsklinik Münster, Klinik und Poliklinik für Neurologie—Entzündliche Erkrankungen des Nervensystems und Neuroonkologie, Münster, Germany
Anja Schrewe, Lore Becker, Valérie Gailus-Durner, Helmut Fuchs, Martin Hrabé de Angelis
Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, München, Germany
Lore Becker, Thomas Klopstock
Friedrich-Baur-Institut an der Neurologischen Klinik, Klinikum der Ludwig-Maximilians-Universität München, München, Germany
Martin Hrabé de Angelis
Lehrstuhl für Experimentelle Genetik, Technische Universität München, Freising-Weihenstephan, Germany
Ajay M. Shah
King's College London School of Medicine, The James Black Centre, Cardiovascular Division, London, United Kingdom

Corresponding Authors

Competing Interests

HHHWS and KW declare a potential competing interest as shareholder and previous employee, respectively, of Vasopharm GmbH, which develops NADPH oxidase inhibitors such as VAS2870. All authors declare that they adhere to all PLoS Biology policies on sharing data and materials as detailed in the PLoS Biology guide for authors.

Author Contributions

The author(s) have made the following declarations about their contributions: Conceived and designed the experiments: CK AS MHdA KJD NW HHS. Performed the experiments: CK HG MEA EJ MM DB TS CG PK KB MKS AMH SGM GS SM AS LB VGD HF TK. Analyzed the data: CK MEA EJ MM DB LB VGD HF TK MHdA KJD NW HHHWS. Contributed reagents/materials/analysis tools: CK HG KW AMS HHHWS. Wrote the paper: CK KW HHHWS.