title: The Neural Cell Adhesion Molecule-Derived (NCAM)-Peptide FG Loop (FGL) Mobilizes Endogenous Neural Stem Cells and Promotes Endogenous Regenerative Capacity after Stroke.
abstract: The neural cell adhesion molecule (NCAM)-derived peptide FG loop (FGL) modulates synaptogenesis, neurogenesis, and stem cell proliferation, enhances cognitive capacities, and conveys neuroprotection after stroke. Here we investigated the effect of subcutaneously injected FGL on cellular compartments affected by degeneration and regeneration after stroke due to middle cerebral artery occlusion (MCAO), namely endogenous neural stem cells (NSC), oligodendrocytes, and microglia. In addition to immunohistochemistry, we used non-invasive positron emission tomography (PET) imaging with the tracer [18F]-fluoro-L-thymidine ([18F]FLT) to visualize endogenous NSC in vivo. FGL significantly increased endogenous NSC mobilization in the neurogenic niches as evidenced by in vivo and ex vivo methods, and it induced remyelination. Moreover, FGL affected neuroinflammation. Extending previous in vitro results, our data show that the NCAM mimetic peptide FGL mobilizes endogenous NSC after focal ischemia and enhances regeneration by amplifying remyelination and modulating neuroinflammation via affecting microglia. Results suggest FGL as a promising candidate to promote recovery after stroke.
authors.affiliation: Department of Neurology, University Hospital of Cologne, Kerpener Strasse 62, 50924, Cologne, Germany. Rebecca.klein@uk-koeln.de.|Max Planck Institute for Metabolism Research, Cologne, Germany. Rebecca.klein@uk-koeln.de.
authors.forename: Rebecca
authors.identifier: 0000-0002-4258-6965
authors.initials: R
authors.lastname: Klein
authors.affiliation: Department of Neurology, University Hospital of Cologne, Kerpener Strasse 62, 50924, Cologne, Germany.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Mahlberg
authors.affiliation: Department of Neurology, University Hospital of Cologne, Kerpener Strasse 62, 50924, Cologne, Germany.
authors.forename: Maurice
authors.initials: M
authors.lastname: Ohren
authors.affiliation: Department of Neurology, University Hospital of Cologne, Kerpener Strasse 62, 50924, Cologne, Germany.|Max Planck Institute for Metabolism Research, Cologne, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Ladwig
authors.affiliation: Max Planck Institute for Metabolism Research, Cologne, Germany.|Department of Nuclear Medicine, University Hospital of Cologne, Cologne, Germany.
authors.forename: Bernd
authors.initials: B
authors.lastname: Neumaier
authors.affiliation: Max Planck Institute for Metabolism Research, Cologne, Germany.
authors.forename: Rudolf
authors.initials: R
authors.lastname: Graf
authors.affiliation: Max Planck Institute for Metabolism Research, Cologne, Germany.
authors.forename: Mathias
authors.initials: M
authors.lastname: Hoehn
authors.affiliation: Enkam Pharmaceuticals A/S, Copenhagen, Denmark.
authors.forename: Morten
authors.initials: M
authors.lastname: Albrechtsen
authors.affiliation: Enkam Pharmaceuticals A/S, Copenhagen, Denmark.
authors.forename: Stephen
authors.initials: S
authors.lastname: Rees
authors.affiliation: Department of Neurology, University Hospital of Cologne, Kerpener Strasse 62, 50924, Cologne, Germany.|Cognitive Neurology Section, Institute of Neuroscience and Medicine (INM-3), Research Centre Juelich, Juelich, Germany.
authors.forename: Gereon Rudolf
authors.initials: GR
authors.lastname: Fink
authors.affiliation: Department of Neurology, University Hospital of Cologne, Kerpener Strasse 62, 50924, Cologne, Germany.|Max Planck Institute for Metabolism Research, Cologne, Germany.|Cognitive Neurology Section, Institute of Neuroscience and Medicine (INM-3), Research Centre Juelich, Juelich, Germany.
authors.forename: Maria Adele
authors.initials: MA
authors.lastname: Rueger
authors.affiliation: Department of Neurology, University Hospital of Cologne, Kerpener Strasse 62, 50924, Cologne, Germany.|Max Planck Institute for Metabolism Research, Cologne, Germany.|Cognitive Neurology Section, Institute of Neuroscience and Medicine (INM-3), Research Centre Juelich, Juelich, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Schroeter
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D007279:Injections, Subcutaneous; D008297:Male; D009416:Nerve Regeneration / Q000187:drug effects / Q000502:physiology*; D019006:Neural Cell Adhesion Molecules / Q000008:administration & dosage*; D058953:Neural Stem Cells / Q000187:drug effects / Q000502:physiology*; D055495:Neurogenesis / Q000187:drug effects / Q000502:physiology*; D010455:Peptides / Q000008:administration & dosage*; D049268:Positron-Emission Tomography / Q000639:trends; D051381:Rats; D017208:Rats, Wistar; D020521:Stroke / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000473:pathology*
chemical_list: C520137:FGLL peptide; D019006:Neural Cell Adhesion Molecules; D010455:Peptides
keywords: FG loop; NCAM; NCAM-derived peptide; Neuroinflammation; Positron-emission-tomography; Regeneration; Stroke; [18F]-fluoro-L-thymidine