Increased Remyelination and Proregenerative Microglia Under Siponimod Therapy in Mechanistic Models.

Animals Azetidines Benzyl Compounds / pharmacology Cuprizone / pharmacology Mice Microglia Remyelination / physiology

Journal

Neurology(R) neuroimmunology & neuroinflammation
ISSN: 2332-7812
Titre abrégé: Neurol Neuroimmunol Neuroinflamm
Pays: United States
ID NLM: 101636388

Informations de publication

Date de publication:
05 2022
Historique:
received: 20 09 2021
accepted: 27 01 2022
entrez: 31 3 2022
pubmed: 1 4 2022
medline: 2 4 2022
Statut: epublish

Résumé

Siponimod is an oral, selective sphingosine-1-phosphate receptor-1/5 modulator approved for treatment of multiple sclerosis. Mouse MRI was used to investigate remyelination in the cuprizone model. We then used a conditional demyelination An increased remyelination was observed in the cuprizone model. Siponimod treatment of demyelinated tadpoles improved remyelination in comparison to control in a bell-shaped dose-response curve. Siponimod in the EAEON model attenuated the clinical score, reduced the retinal degeneration, and improved the visual function after prophylactic and therapeutic treatment, also in a bell-shaped manner. Inflammatory infiltrates and demyelination of the optic nerve were reduced, the latter even after therapeutic treatment, which also shifted microglial differentiation to a promyelinating phenotype. These results confirm the immunomodulatory effects of siponimod and suggest additional regenerative and promyelinating effects, which follow the dynamics of a bell-shaped curve with high being less efficient than low concentrations.

Sections du résumé

BACKGROUND AND OBJECTIVES
Siponimod is an oral, selective sphingosine-1-phosphate receptor-1/5 modulator approved for treatment of multiple sclerosis.
METHODS
Mouse MRI was used to investigate remyelination in the cuprizone model. We then used a conditional demyelination
RESULTS
An increased remyelination was observed in the cuprizone model. Siponimod treatment of demyelinated tadpoles improved remyelination in comparison to control in a bell-shaped dose-response curve. Siponimod in the EAEON model attenuated the clinical score, reduced the retinal degeneration, and improved the visual function after prophylactic and therapeutic treatment, also in a bell-shaped manner. Inflammatory infiltrates and demyelination of the optic nerve were reduced, the latter even after therapeutic treatment, which also shifted microglial differentiation to a promyelinating phenotype.
DISCUSSION
These results confirm the immunomodulatory effects of siponimod and suggest additional regenerative and promyelinating effects, which follow the dynamics of a bell-shaped curve with high being less efficient than low concentrations.

Identifiants

DOI: 10.1212/NXI.0000000000001161 PMID: 35354603 PMC: PMC8969301
pubmed: 35354603
pii: 9/3/e1161
doi: 10.1212/NXI.0000000000001161
pmc: PMC8969301
pii:
doi:

Substances chimiques

Azetidines 0
Benzyl Compounds 0
Cuprizone 5N16U7E0AO
siponimod RR6P8L282I

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

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Auteurs

Michael Dietrich (M)

From the Department of Neurology (M.D., C.H., M.G., J.G., P.G., A.I., M.N., H.-P.H., P.K., S.G.M.), Heinrich Heine University Düsseldorf, Medical Faculty (P.A.), Düsseldorf, Germany; Sorbonne Université (E.M., D.L., B.S., C.L., D.A., B.Z.), Inserm, CNRS, Institut du Cerveau, Pitié-Salpêtrière Hospital; AP-HP (B.S.), Saint-Antoine Hospital; AP-HP (C.L.), Pitié-Salpêtrière Hospital, Paris, France; Novartis Institutes for BioMedical Research (P.R., C.B., S.T., N.B., D.S., M.B.), Basel, Switzerland; Biological and Medical Research Center (BMFZ) (P.P., K.K.), Heinrich Heine University Düsseldorf, Medical Faculty; Institute for Molecular Medicine III (B.L.), University Hospital Düsseldorf and Heinrich Heine University Düsseldorf; Institute of Pharmaceutical and Medicinal Chemistry (H.S.), Heinrich Heine University Düsseldorf, Duesseldorf, Germany; Brain and Mind Center (H.-P.H.), University of Sydney, NSW, Australia; and Medical University of Vienna (H.-P.H.), Vienna, Austria.

Christina Hecker (C)

From the Department of Neurology (M.D., C.H., M.G., J.G., P.G., A.I., M.N., H.-P.H., P.K., S.G.M.), Heinrich Heine University Düsseldorf, Medical Faculty (P.A.), Düsseldorf, Germany; Sorbonne Université (E.M., D.L., B.S., C.L., D.A., B.Z.), Inserm, CNRS, Institut du Cerveau, Pitié-Salpêtrière Hospital; AP-HP (B.S.), Saint-Antoine Hospital; AP-HP (C.L.), Pitié-Salpêtrière Hospital, Paris, France; Novartis Institutes for BioMedical Research (P.R., C.B., S.T., N.B., D.S., M.B.), Basel, Switzerland; Biological and Medical Research Center (BMFZ) (P.P., K.K.), Heinrich Heine University Düsseldorf, Medical Faculty; Institute for Molecular Medicine III (B.L.), University Hospital Düsseldorf and Heinrich Heine University Düsseldorf; Institute of Pharmaceutical and Medicinal Chemistry (H.S.), Heinrich Heine University Düsseldorf, Duesseldorf, Germany; Brain and Mind Center (H.-P.H.), University of Sydney, NSW, Australia; and Medical University of Vienna (H.-P.H.), Vienna, Austria.

Elodie Martin (E)

From the Department of Neurology (M.D., C.H., M.G., J.G., P.G., A.I., M.N., H.-P.H., P.K., S.G.M.), Heinrich Heine University Düsseldorf, Medical Faculty (P.A.), Düsseldorf, Germany; Sorbonne Université (E.M., D.L., B.S., C.L., D.A., B.Z.), Inserm, CNRS, Institut du Cerveau, Pitié-Salpêtrière Hospital; AP-HP (B.S.), Saint-Antoine Hospital; AP-HP (C.L.), Pitié-Salpêtrière Hospital, Paris, France; Novartis Institutes for BioMedical Research (P.R., C.B., S.T., N.B., D.S., M.B.), Basel, Switzerland; Biological and Medical Research Center (BMFZ) (P.P., K.K.), Heinrich Heine University Düsseldorf, Medical Faculty; Institute for Molecular Medicine III (B.L.), University Hospital Düsseldorf and Heinrich Heine University Düsseldorf; Institute of Pharmaceutical and Medicinal Chemistry (H.S.), Heinrich Heine University Düsseldorf, Duesseldorf, Germany; Brain and Mind Center (H.-P.H.), University of Sydney, NSW, Australia; and Medical University of Vienna (H.-P.H.), Vienna, Austria.

Dominique Langui (D)

From the Department of Neurology (M.D., C.H., M.G., J.G., P.G., A.I., M.N., H.-P.H., P.K., S.G.M.), Heinrich Heine University Düsseldorf, Medical Faculty (P.A.), Düsseldorf, Germany; Sorbonne Université (E.M., D.L., B.S., C.L., D.A., B.Z.), Inserm, CNRS, Institut du Cerveau, Pitié-Salpêtrière Hospital; AP-HP (B.S.), Saint-Antoine Hospital; AP-HP (C.L.), Pitié-Salpêtrière Hospital, Paris, France; Novartis Institutes for BioMedical Research (P.R., C.B., S.T., N.B., D.S., M.B.), Basel, Switzerland; Biological and Medical Research Center (BMFZ) (P.P., K.K.), Heinrich Heine University Düsseldorf, Medical Faculty; Institute for Molecular Medicine III (B.L.), University Hospital Düsseldorf and Heinrich Heine University Düsseldorf; Institute of Pharmaceutical and Medicinal Chemistry (H.S.), Heinrich Heine University Düsseldorf, Duesseldorf, Germany; Brain and Mind Center (H.-P.H.), University of Sydney, NSW, Australia; and Medical University of Vienna (H.-P.H.), Vienna, Austria.

Michael Gliem (M)

From the Department of Neurology (M.D., C.H., M.G., J.G., P.G., A.I., M.N., H.-P.H., P.K., S.G.M.), Heinrich Heine University Düsseldorf, Medical Faculty (P.A.), Düsseldorf, Germany; Sorbonne Université (E.M., D.L., B.S., C.L., D.A., B.Z.), Inserm, CNRS, Institut du Cerveau, Pitié-Salpêtrière Hospital; AP-HP (B.S.), Saint-Antoine Hospital; AP-HP (C.L.), Pitié-Salpêtrière Hospital, Paris, France; Novartis Institutes for BioMedical Research (P.R., C.B., S.T., N.B., D.S., M.B.), Basel, Switzerland; Biological and Medical Research Center (BMFZ) (P.P., K.K.), Heinrich Heine University Düsseldorf, Medical Faculty; Institute for Molecular Medicine III (B.L.), University Hospital Düsseldorf and Heinrich Heine University Düsseldorf; Institute of Pharmaceutical and Medicinal Chemistry (H.S.), Heinrich Heine University Düsseldorf, Duesseldorf, Germany; Brain and Mind Center (H.-P.H.), University of Sydney, NSW, Australia; and Medical University of Vienna (H.-P.H.), Vienna, Austria.

Bruno Stankoff (B)

From the Department of Neurology (M.D., C.H., M.G., J.G., P.G., A.I., M.N., H.-P.H., P.K., S.G.M.), Heinrich Heine University Düsseldorf, Medical Faculty (P.A.), Düsseldorf, Germany; Sorbonne Université (E.M., D.L., B.S., C.L., D.A., B.Z.), Inserm, CNRS, Institut du Cerveau, Pitié-Salpêtrière Hospital; AP-HP (B.S.), Saint-Antoine Hospital; AP-HP (C.L.), Pitié-Salpêtrière Hospital, Paris, France; Novartis Institutes for BioMedical Research (P.R., C.B., S.T., N.B., D.S., M.B.), Basel, Switzerland; Biological and Medical Research Center (BMFZ) (P.P., K.K.), Heinrich Heine University Düsseldorf, Medical Faculty; Institute for Molecular Medicine III (B.L.), University Hospital Düsseldorf and Heinrich Heine University Düsseldorf; Institute of Pharmaceutical and Medicinal Chemistry (H.S.), Heinrich Heine University Düsseldorf, Duesseldorf, Germany; Brain and Mind Center (H.-P.H.), University of Sydney, NSW, Australia; and Medical University of Vienna (H.-P.H.), Vienna, Austria.

Catherine Lubetzki (C)

From the Department of Neurology (M.D., C.H., M.G., J.G., P.G., A.I., M.N., H.-P.H., P.K., S.G.M.), Heinrich Heine University Düsseldorf, Medical Faculty (P.A.), Düsseldorf, Germany; Sorbonne Université (E.M., D.L., B.S., C.L., D.A., B.Z.), Inserm, CNRS, Institut du Cerveau, Pitié-Salpêtrière Hospital; AP-HP (B.S.), Saint-Antoine Hospital; AP-HP (C.L.), Pitié-Salpêtrière Hospital, Paris, France; Novartis Institutes for BioMedical Research (P.R., C.B., S.T., N.B., D.S., M.B.), Basel, Switzerland; Biological and Medical Research Center (BMFZ) (P.P., K.K.), Heinrich Heine University Düsseldorf, Medical Faculty; Institute for Molecular Medicine III (B.L.), University Hospital Düsseldorf and Heinrich Heine University Düsseldorf; Institute of Pharmaceutical and Medicinal Chemistry (H.S.), Heinrich Heine University Düsseldorf, Duesseldorf, Germany; Brain and Mind Center (H.-P.H.), University of Sydney, NSW, Australia; and Medical University of Vienna (H.-P.H.), Vienna, Austria.

Joel Gruchot (J)

From the Department of Neurology (M.D., C.H., M.G., J.G., P.G., A.I., M.N., H.-P.H., P.K., S.G.M.), Heinrich Heine University Düsseldorf, Medical Faculty (P.A.), Düsseldorf, Germany; Sorbonne Université (E.M., D.L., B.S., C.L., D.A., B.Z.), Inserm, CNRS, Institut du Cerveau, Pitié-Salpêtrière Hospital; AP-HP (B.S.), Saint-Antoine Hospital; AP-HP (C.L.), Pitié-Salpêtrière Hospital, Paris, France; Novartis Institutes for BioMedical Research (P.R., C.B., S.T., N.B., D.S., M.B.), Basel, Switzerland; Biological and Medical Research Center (BMFZ) (P.P., K.K.), Heinrich Heine University Düsseldorf, Medical Faculty; Institute for Molecular Medicine III (B.L.), University Hospital Düsseldorf and Heinrich Heine University Düsseldorf; Institute of Pharmaceutical and Medicinal Chemistry (H.S.), Heinrich Heine University Düsseldorf, Duesseldorf, Germany; Brain and Mind Center (H.-P.H.), University of Sydney, NSW, Australia; and Medical University of Vienna (H.-P.H.), Vienna, Austria.

Peter Göttle (P)

From the Department of Neurology (M.D., C.H., M.G., J.G., P.G., A.I., M.N., H.-P.H., P.K., S.G.M.), Heinrich Heine University Düsseldorf, Medical Faculty (P.A.), Düsseldorf, Germany; Sorbonne Université (E.M., D.L., B.S., C.L., D.A., B.Z.), Inserm, CNRS, Institut du Cerveau, Pitié-Salpêtrière Hospital; AP-HP (B.S.), Saint-Antoine Hospital; AP-HP (C.L.), Pitié-Salpêtrière Hospital, Paris, France; Novartis Institutes for BioMedical Research (P.R., C.B., S.T., N.B., D.S., M.B.), Basel, Switzerland; Biological and Medical Research Center (BMFZ) (P.P., K.K.), Heinrich Heine University Düsseldorf, Medical Faculty; Institute for Molecular Medicine III (B.L.), University Hospital Düsseldorf and Heinrich Heine University Düsseldorf; Institute of Pharmaceutical and Medicinal Chemistry (H.S.), Heinrich Heine University Düsseldorf, Duesseldorf, Germany; Brain and Mind Center (H.-P.H.), University of Sydney, NSW, Australia; and Medical University of Vienna (H.-P.H.), Vienna, Austria.

Andrea Issberner (A)

From the Department of Neurology (M.D., C.H., M.G., J.G., P.G., A.I., M.N., H.-P.H., P.K., S.G.M.), Heinrich Heine University Düsseldorf, Medical Faculty (P.A.), Düsseldorf, Germany; Sorbonne Université (E.M., D.L., B.S., C.L., D.A., B.Z.), Inserm, CNRS, Institut du Cerveau, Pitié-Salpêtrière Hospital; AP-HP (B.S.), Saint-Antoine Hospital; AP-HP (C.L.), Pitié-Salpêtrière Hospital, Paris, France; Novartis Institutes for BioMedical Research (P.R., C.B., S.T., N.B., D.S., M.B.), Basel, Switzerland; Biological and Medical Research Center (BMFZ) (P.P., K.K.), Heinrich Heine University Düsseldorf, Medical Faculty; Institute for Molecular Medicine III (B.L.), University Hospital Düsseldorf and Heinrich Heine University Düsseldorf; Institute of Pharmaceutical and Medicinal Chemistry (H.S.), Heinrich Heine University Düsseldorf, Duesseldorf, Germany; Brain and Mind Center (H.-P.H.), University of Sydney, NSW, Australia; and Medical University of Vienna (H.-P.H.), Vienna, Austria.

Milad Nasiri (M)

From the Department of Neurology (M.D., C.H., M.G., J.G., P.G., A.I., M.N., H.-P.H., P.K., S.G.M.), Heinrich Heine University Düsseldorf, Medical Faculty (P.A.), Düsseldorf, Germany; Sorbonne Université (E.M., D.L., B.S., C.L., D.A., B.Z.), Inserm, CNRS, Institut du Cerveau, Pitié-Salpêtrière Hospital; AP-HP (B.S.), Saint-Antoine Hospital; AP-HP (C.L.), Pitié-Salpêtrière Hospital, Paris, France; Novartis Institutes for BioMedical Research (P.R., C.B., S.T., N.B., D.S., M.B.), Basel, Switzerland; Biological and Medical Research Center (BMFZ) (P.P., K.K.), Heinrich Heine University Düsseldorf, Medical Faculty; Institute for Molecular Medicine III (B.L.), University Hospital Düsseldorf and Heinrich Heine University Düsseldorf; Institute of Pharmaceutical and Medicinal Chemistry (H.S.), Heinrich Heine University Düsseldorf, Duesseldorf, Germany; Brain and Mind Center (H.-P.H.), University of Sydney, NSW, Australia; and Medical University of Vienna (H.-P.H.), Vienna, Austria.

Pamela Ramseier (P)

From the Department of Neurology (M.D., C.H., M.G., J.G., P.G., A.I., M.N., H.-P.H., P.K., S.G.M.), Heinrich Heine University Düsseldorf, Medical Faculty (P.A.), Düsseldorf, Germany; Sorbonne Université (E.M., D.L., B.S., C.L., D.A., B.Z.), Inserm, CNRS, Institut du Cerveau, Pitié-Salpêtrière Hospital; AP-HP (B.S.), Saint-Antoine Hospital; AP-HP (C.L.), Pitié-Salpêtrière Hospital, Paris, France; Novartis Institutes for BioMedical Research (P.R., C.B., S.T., N.B., D.S., M.B.), Basel, Switzerland; Biological and Medical Research Center (BMFZ) (P.P., K.K.), Heinrich Heine University Düsseldorf, Medical Faculty; Institute for Molecular Medicine III (B.L.), University Hospital Düsseldorf and Heinrich Heine University Düsseldorf; Institute of Pharmaceutical and Medicinal Chemistry (H.S.), Heinrich Heine University Düsseldorf, Duesseldorf, Germany; Brain and Mind Center (H.-P.H.), University of Sydney, NSW, Australia; and Medical University of Vienna (H.-P.H.), Vienna, Austria.

Christian Beerli (C)

From the Department of Neurology (M.D., C.H., M.G., J.G., P.G., A.I., M.N., H.-P.H., P.K., S.G.M.), Heinrich Heine University Düsseldorf, Medical Faculty (P.A.), Düsseldorf, Germany; Sorbonne Université (E.M., D.L., B.S., C.L., D.A., B.Z.), Inserm, CNRS, Institut du Cerveau, Pitié-Salpêtrière Hospital; AP-HP (B.S.), Saint-Antoine Hospital; AP-HP (C.L.), Pitié-Salpêtrière Hospital, Paris, France; Novartis Institutes for BioMedical Research (P.R., C.B., S.T., N.B., D.S., M.B.), Basel, Switzerland; Biological and Medical Research Center (BMFZ) (P.P., K.K.), Heinrich Heine University Düsseldorf, Medical Faculty; Institute for Molecular Medicine III (B.L.), University Hospital Düsseldorf and Heinrich Heine University Düsseldorf; Institute of Pharmaceutical and Medicinal Chemistry (H.S.), Heinrich Heine University Düsseldorf, Duesseldorf, Germany; Brain and Mind Center (H.-P.H.), University of Sydney, NSW, Australia; and Medical University of Vienna (H.-P.H.), Vienna, Austria.

Sarah Tisserand (S)

From the Department of Neurology (M.D., C.H., M.G., J.G., P.G., A.I., M.N., H.-P.H., P.K., S.G.M.), Heinrich Heine University Düsseldorf, Medical Faculty (P.A.), Düsseldorf, Germany; Sorbonne Université (E.M., D.L., B.S., C.L., D.A., B.Z.), Inserm, CNRS, Institut du Cerveau, Pitié-Salpêtrière Hospital; AP-HP (B.S.), Saint-Antoine Hospital; AP-HP (C.L.), Pitié-Salpêtrière Hospital, Paris, France; Novartis Institutes for BioMedical Research (P.R., C.B., S.T., N.B., D.S., M.B.), Basel, Switzerland; Biological and Medical Research Center (BMFZ) (P.P., K.K.), Heinrich Heine University Düsseldorf, Medical Faculty; Institute for Molecular Medicine III (B.L.), University Hospital Düsseldorf and Heinrich Heine University Düsseldorf; Institute of Pharmaceutical and Medicinal Chemistry (H.S.), Heinrich Heine University Düsseldorf, Duesseldorf, Germany; Brain and Mind Center (H.-P.H.), University of Sydney, NSW, Australia; and Medical University of Vienna (H.-P.H.), Vienna, Austria.

Nicolau Beckmann (N)

From the Department of Neurology (M.D., C.H., M.G., J.G., P.G., A.I., M.N., H.-P.H., P.K., S.G.M.), Heinrich Heine University Düsseldorf, Medical Faculty (P.A.), Düsseldorf, Germany; Sorbonne Université (E.M., D.L., B.S., C.L., D.A., B.Z.), Inserm, CNRS, Institut du Cerveau, Pitié-Salpêtrière Hospital; AP-HP (B.S.), Saint-Antoine Hospital; AP-HP (C.L.), Pitié-Salpêtrière Hospital, Paris, France; Novartis Institutes for BioMedical Research (P.R., C.B., S.T., N.B., D.S., M.B.), Basel, Switzerland; Biological and Medical Research Center (BMFZ) (P.P., K.K.), Heinrich Heine University Düsseldorf, Medical Faculty; Institute for Molecular Medicine III (B.L.), University Hospital Düsseldorf and Heinrich Heine University Düsseldorf; Institute of Pharmaceutical and Medicinal Chemistry (H.S.), Heinrich Heine University Düsseldorf, Duesseldorf, Germany; Brain and Mind Center (H.-P.H.), University of Sydney, NSW, Australia; and Medical University of Vienna (H.-P.H.), Vienna, Austria.

Derya Shimshek (D)

From the Department of Neurology (M.D., C.H., M.G., J.G., P.G., A.I., M.N., H.-P.H., P.K., S.G.M.), Heinrich Heine University Düsseldorf, Medical Faculty (P.A.), Düsseldorf, Germany; Sorbonne Université (E.M., D.L., B.S., C.L., D.A., B.Z.), Inserm, CNRS, Institut du Cerveau, Pitié-Salpêtrière Hospital; AP-HP (B.S.), Saint-Antoine Hospital; AP-HP (C.L.), Pitié-Salpêtrière Hospital, Paris, France; Novartis Institutes for BioMedical Research (P.R., C.B., S.T., N.B., D.S., M.B.), Basel, Switzerland; Biological and Medical Research Center (BMFZ) (P.P., K.K.), Heinrich Heine University Düsseldorf, Medical Faculty; Institute for Molecular Medicine III (B.L.), University Hospital Düsseldorf and Heinrich Heine University Düsseldorf; Institute of Pharmaceutical and Medicinal Chemistry (H.S.), Heinrich Heine University Düsseldorf, Duesseldorf, Germany; Brain and Mind Center (H.-P.H.), University of Sydney, NSW, Australia; and Medical University of Vienna (H.-P.H.), Vienna, Austria.

Patrick Petzsch (P)

From the Department of Neurology (M.D., C.H., M.G., J.G., P.G., A.I., M.N., H.-P.H., P.K., S.G.M.), Heinrich Heine University Düsseldorf, Medical Faculty (P.A.), Düsseldorf, Germany; Sorbonne Université (E.M., D.L., B.S., C.L., D.A., B.Z.), Inserm, CNRS, Institut du Cerveau, Pitié-Salpêtrière Hospital; AP-HP (B.S.), Saint-Antoine Hospital; AP-HP (C.L.), Pitié-Salpêtrière Hospital, Paris, France; Novartis Institutes for BioMedical Research (P.R., C.B., S.T., N.B., D.S., M.B.), Basel, Switzerland; Biological and Medical Research Center (BMFZ) (P.P., K.K.), Heinrich Heine University Düsseldorf, Medical Faculty; Institute for Molecular Medicine III (B.L.), University Hospital Düsseldorf and Heinrich Heine University Düsseldorf; Institute of Pharmaceutical and Medicinal Chemistry (H.S.), Heinrich Heine University Düsseldorf, Duesseldorf, Germany; Brain and Mind Center (H.-P.H.), University of Sydney, NSW, Australia; and Medical University of Vienna (H.-P.H.), Vienna, Austria.

David Akbar (D)

From the Department of Neurology (M.D., C.H., M.G., J.G., P.G., A.I., M.N., H.-P.H., P.K., S.G.M.), Heinrich Heine University Düsseldorf, Medical Faculty (P.A.), Düsseldorf, Germany; Sorbonne Université (E.M., D.L., B.S., C.L., D.A., B.Z.), Inserm, CNRS, Institut du Cerveau, Pitié-Salpêtrière Hospital; AP-HP (B.S.), Saint-Antoine Hospital; AP-HP (C.L.), Pitié-Salpêtrière Hospital, Paris, France; Novartis Institutes for BioMedical Research (P.R., C.B., S.T., N.B., D.S., M.B.), Basel, Switzerland; Biological and Medical Research Center (BMFZ) (P.P., K.K.), Heinrich Heine University Düsseldorf, Medical Faculty; Institute for Molecular Medicine III (B.L.), University Hospital Düsseldorf and Heinrich Heine University Düsseldorf; Institute of Pharmaceutical and Medicinal Chemistry (H.S.), Heinrich Heine University Düsseldorf, Duesseldorf, Germany; Brain and Mind Center (H.-P.H.), University of Sydney, NSW, Australia; and Medical University of Vienna (H.-P.H.), Vienna, Austria.

Bodo Levkau (B)

From the Department of Neurology (M.D., C.H., M.G., J.G., P.G., A.I., M.N., H.-P.H., P.K., S.G.M.), Heinrich Heine University Düsseldorf, Medical Faculty (P.A.), Düsseldorf, Germany; Sorbonne Université (E.M., D.L., B.S., C.L., D.A., B.Z.), Inserm, CNRS, Institut du Cerveau, Pitié-Salpêtrière Hospital; AP-HP (B.S.), Saint-Antoine Hospital; AP-HP (C.L.), Pitié-Salpêtrière Hospital, Paris, France; Novartis Institutes for BioMedical Research (P.R., C.B., S.T., N.B., D.S., M.B.), Basel, Switzerland; Biological and Medical Research Center (BMFZ) (P.P., K.K.), Heinrich Heine University Düsseldorf, Medical Faculty; Institute for Molecular Medicine III (B.L.), University Hospital Düsseldorf and Heinrich Heine University Düsseldorf; Institute of Pharmaceutical and Medicinal Chemistry (H.S.), Heinrich Heine University Düsseldorf, Duesseldorf, Germany; Brain and Mind Center (H.-P.H.), University of Sydney, NSW, Australia; and Medical University of Vienna (H.-P.H.), Vienna, Austria.

Holger Stark (H)

From the Department of Neurology (M.D., C.H., M.G., J.G., P.G., A.I., M.N., H.-P.H., P.K., S.G.M.), Heinrich Heine University Düsseldorf, Medical Faculty (P.A.), Düsseldorf, Germany; Sorbonne Université (E.M., D.L., B.S., C.L., D.A., B.Z.), Inserm, CNRS, Institut du Cerveau, Pitié-Salpêtrière Hospital; AP-HP (B.S.), Saint-Antoine Hospital; AP-HP (C.L.), Pitié-Salpêtrière Hospital, Paris, France; Novartis Institutes for BioMedical Research (P.R., C.B., S.T., N.B., D.S., M.B.), Basel, Switzerland; Biological and Medical Research Center (BMFZ) (P.P., K.K.), Heinrich Heine University Düsseldorf, Medical Faculty; Institute for Molecular Medicine III (B.L.), University Hospital Düsseldorf and Heinrich Heine University Düsseldorf; Institute of Pharmaceutical and Medicinal Chemistry (H.S.), Heinrich Heine University Düsseldorf, Duesseldorf, Germany; Brain and Mind Center (H.-P.H.), University of Sydney, NSW, Australia; and Medical University of Vienna (H.-P.H.), Vienna, Austria.

Karl Köhrer (K)

From the Department of Neurology (M.D., C.H., M.G., J.G., P.G., A.I., M.N., H.-P.H., P.K., S.G.M.), Heinrich Heine University Düsseldorf, Medical Faculty (P.A.), Düsseldorf, Germany; Sorbonne Université (E.M., D.L., B.S., C.L., D.A., B.Z.), Inserm, CNRS, Institut du Cerveau, Pitié-Salpêtrière Hospital; AP-HP (B.S.), Saint-Antoine Hospital; AP-HP (C.L.), Pitié-Salpêtrière Hospital, Paris, France; Novartis Institutes for BioMedical Research (P.R., C.B., S.T., N.B., D.S., M.B.), Basel, Switzerland; Biological and Medical Research Center (BMFZ) (P.P., K.K.), Heinrich Heine University Düsseldorf, Medical Faculty; Institute for Molecular Medicine III (B.L.), University Hospital Düsseldorf and Heinrich Heine University Düsseldorf; Institute of Pharmaceutical and Medicinal Chemistry (H.S.), Heinrich Heine University Düsseldorf, Duesseldorf, Germany; Brain and Mind Center (H.-P.H.), University of Sydney, NSW, Australia; and Medical University of Vienna (H.-P.H.), Vienna, Austria.

Hans-Peter Hartung (HP)

From the Department of Neurology (M.D., C.H., M.G., J.G., P.G., A.I., M.N., H.-P.H., P.K., S.G.M.), Heinrich Heine University Düsseldorf, Medical Faculty (P.A.), Düsseldorf, Germany; Sorbonne Université (E.M., D.L., B.S., C.L., D.A., B.Z.), Inserm, CNRS, Institut du Cerveau, Pitié-Salpêtrière Hospital; AP-HP (B.S.), Saint-Antoine Hospital; AP-HP (C.L.), Pitié-Salpêtrière Hospital, Paris, France; Novartis Institutes for BioMedical Research (P.R., C.B., S.T., N.B., D.S., M.B.), Basel, Switzerland; Biological and Medical Research Center (BMFZ) (P.P., K.K.), Heinrich Heine University Düsseldorf, Medical Faculty; Institute for Molecular Medicine III (B.L.), University Hospital Düsseldorf and Heinrich Heine University Düsseldorf; Institute of Pharmaceutical and Medicinal Chemistry (H.S.), Heinrich Heine University Düsseldorf, Duesseldorf, Germany; Brain and Mind Center (H.-P.H.), University of Sydney, NSW, Australia; and Medical University of Vienna (H.-P.H.), Vienna, Austria.

Patrick Küry (P)

From the Department of Neurology (M.D., C.H., M.G., J.G., P.G., A.I., M.N., H.-P.H., P.K., S.G.M.), Heinrich Heine University Düsseldorf, Medical Faculty (P.A.), Düsseldorf, Germany; Sorbonne Université (E.M., D.L., B.S., C.L., D.A., B.Z.), Inserm, CNRS, Institut du Cerveau, Pitié-Salpêtrière Hospital; AP-HP (B.S.), Saint-Antoine Hospital; AP-HP (C.L.), Pitié-Salpêtrière Hospital, Paris, France; Novartis Institutes for BioMedical Research (P.R., C.B., S.T., N.B., D.S., M.B.), Basel, Switzerland; Biological and Medical Research Center (BMFZ) (P.P., K.K.), Heinrich Heine University Düsseldorf, Medical Faculty; Institute for Molecular Medicine III (B.L.), University Hospital Düsseldorf and Heinrich Heine University Düsseldorf; Institute of Pharmaceutical and Medicinal Chemistry (H.S.), Heinrich Heine University Düsseldorf, Duesseldorf, Germany; Brain and Mind Center (H.-P.H.), University of Sydney, NSW, Australia; and Medical University of Vienna (H.-P.H.), Vienna, Austria.

Sven Günther Meuth (SG)

From the Department of Neurology (M.D., C.H., M.G., J.G., P.G., A.I., M.N., H.-P.H., P.K., S.G.M.), Heinrich Heine University Düsseldorf, Medical Faculty (P.A.), Düsseldorf, Germany; Sorbonne Université (E.M., D.L., B.S., C.L., D.A., B.Z.), Inserm, CNRS, Institut du Cerveau, Pitié-Salpêtrière Hospital; AP-HP (B.S.), Saint-Antoine Hospital; AP-HP (C.L.), Pitié-Salpêtrière Hospital, Paris, France; Novartis Institutes for BioMedical Research (P.R., C.B., S.T., N.B., D.S., M.B.), Basel, Switzerland; Biological and Medical Research Center (BMFZ) (P.P., K.K.), Heinrich Heine University Düsseldorf, Medical Faculty; Institute for Molecular Medicine III (B.L.), University Hospital Düsseldorf and Heinrich Heine University Düsseldorf; Institute of Pharmaceutical and Medicinal Chemistry (H.S.), Heinrich Heine University Düsseldorf, Duesseldorf, Germany; Brain and Mind Center (H.-P.H.), University of Sydney, NSW, Australia; and Medical University of Vienna (H.-P.H.), Vienna, Austria.

Marc Bigaud (M)

From the Department of Neurology (M.D., C.H., M.G., J.G., P.G., A.I., M.N., H.-P.H., P.K., S.G.M.), Heinrich Heine University Düsseldorf, Medical Faculty (P.A.), Düsseldorf, Germany; Sorbonne Université (E.M., D.L., B.S., C.L., D.A., B.Z.), Inserm, CNRS, Institut du Cerveau, Pitié-Salpêtrière Hospital; AP-HP (B.S.), Saint-Antoine Hospital; AP-HP (C.L.), Pitié-Salpêtrière Hospital, Paris, France; Novartis Institutes for BioMedical Research (P.R., C.B., S.T., N.B., D.S., M.B.), Basel, Switzerland; Biological and Medical Research Center (BMFZ) (P.P., K.K.), Heinrich Heine University Düsseldorf, Medical Faculty; Institute for Molecular Medicine III (B.L.), University Hospital Düsseldorf and Heinrich Heine University Düsseldorf; Institute of Pharmaceutical and Medicinal Chemistry (H.S.), Heinrich Heine University Düsseldorf, Duesseldorf, Germany; Brain and Mind Center (H.-P.H.), University of Sydney, NSW, Australia; and Medical University of Vienna (H.-P.H.), Vienna, Austria.

Bernard Zalc (B)

From the Department of Neurology (M.D., C.H., M.G., J.G., P.G., A.I., M.N., H.-P.H., P.K., S.G.M.), Heinrich Heine University Düsseldorf, Medical Faculty (P.A.), Düsseldorf, Germany; Sorbonne Université (E.M., D.L., B.S., C.L., D.A., B.Z.), Inserm, CNRS, Institut du Cerveau, Pitié-Salpêtrière Hospital; AP-HP (B.S.), Saint-Antoine Hospital; AP-HP (C.L.), Pitié-Salpêtrière Hospital, Paris, France; Novartis Institutes for BioMedical Research (P.R., C.B., S.T., N.B., D.S., M.B.), Basel, Switzerland; Biological and Medical Research Center (BMFZ) (P.P., K.K.), Heinrich Heine University Düsseldorf, Medical Faculty; Institute for Molecular Medicine III (B.L.), University Hospital Düsseldorf and Heinrich Heine University Düsseldorf; Institute of Pharmaceutical and Medicinal Chemistry (H.S.), Heinrich Heine University Düsseldorf, Duesseldorf, Germany; Brain and Mind Center (H.-P.H.), University of Sydney, NSW, Australia; and Medical University of Vienna (H.-P.H.), Vienna, Austria.

Philipp Albrecht (P)

From the Department of Neurology (M.D., C.H., M.G., J.G., P.G., A.I., M.N., H.-P.H., P.K., S.G.M.), Heinrich Heine University Düsseldorf, Medical Faculty (P.A.), Düsseldorf, Germany; Sorbonne Université (E.M., D.L., B.S., C.L., D.A., B.Z.), Inserm, CNRS, Institut du Cerveau, Pitié-Salpêtrière Hospital; AP-HP (B.S.), Saint-Antoine Hospital; AP-HP (C.L.), Pitié-Salpêtrière Hospital, Paris, France; Novartis Institutes for BioMedical Research (P.R., C.B., S.T., N.B., D.S., M.B.), Basel, Switzerland; Biological and Medical Research Center (BMFZ) (P.P., K.K.), Heinrich Heine University Düsseldorf, Medical Faculty; Institute for Molecular Medicine III (B.L.), University Hospital Düsseldorf and Heinrich Heine University Düsseldorf; Institute of Pharmaceutical and Medicinal Chemistry (H.S.), Heinrich Heine University Düsseldorf, Duesseldorf, Germany; Brain and Mind Center (H.-P.H.), University of Sydney, NSW, Australia; and Medical University of Vienna (H.-P.H.), Vienna, Austria.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Increased Remyelination and Proregenerative...
questionsmedicales.fr › Composés hétérocycliques › Composés hétéromonocycliques › Azétines › Azétidines › Increased Remyelination and Proregenerative...
questionsmedicales.fr › Composés chimiques organiques › Hydrocarbures › Hydrocarbures cycliques › Hydrocarbures aromatiques › Dérivés du benzène › Composés benzyliques › Increased Remyelination and Proregenerative...
questionsmedicales.fr › Composés chimiques organiques › Hydrocarbures › Hydrocarbures cycliques › Hydrocarbures alicycliques › Cyclohexanes › Cuprizone › Increased Remyelination and Proregenerative...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Increased Remyelination and Proregenerative...
questionsmedicales.fr › Cellules › Névroglie › Microglie › Increased Remyelination and Proregenerative...
questionsmedicales.fr › Phénomènes biologiques › Régénération › Régénération nerveuse › Remyélinisation › Increased Remyelination and Proregenerative...