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The Neural Cell Adhesion Molecule-Derived (NCAM)-Peptide FG Loop (FGL) Mobilizes Endogenous Neural Stem Cells and Promotes Endogenous Regenerative Capacity after Stroke

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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.

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Acknowledgments

This research work has been supported by the European Community’s Seventh Framework Programme ‘NeuroFGL’ (#2780006), by the ‘Marga und Walter Boll-Stiftung (#210-12-12 and #210-10-15), and ‘Koeln Fortune’ (#13/2014). We thank Ms. Claudia Drapatz for excellent technical assistance.

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Authors and Affiliations

  1. Department of Neurology, University Hospital of Cologne, Kerpener Strasse 62, 50924, Cologne, Germany

    Rebecca Klein, Nicolas Mahlberg, Maurice Ohren, Anne Ladwig, Gereon Rudolf Fink, Maria Adele Rueger & Michael Schroeter

  2. Max Planck Institute for Metabolism Research, Cologne, Germany

    Rebecca Klein, Anne Ladwig, Bernd Neumaier, Rudolf Graf, Mathias Hoehn, Maria Adele Rueger & Michael Schroeter

  3. Department of Nuclear Medicine, University Hospital of Cologne, Cologne, Germany

    Bernd Neumaier

  4. Enkam Pharmaceuticals A/S, Copenhagen, Denmark

    Morten Albrechtsen & Stephen Rees

  5. Cognitive Neurology Section, Institute of Neuroscience and Medicine (INM-3), Research Centre Juelich, Juelich, Germany

    Gereon Rudolf Fink, Maria Adele Rueger & Michael Schroeter

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  1. Rebecca Klein
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  2. Nicolas Mahlberg
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  3. Maurice Ohren
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  10. Gereon Rudolf Fink
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Correspondence to Rebecca Klein.

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Klein, R., Mahlberg, N., Ohren, M. et al. The Neural Cell Adhesion Molecule-Derived (NCAM)-Peptide FG Loop (FGL) Mobilizes Endogenous Neural Stem Cells and Promotes Endogenous Regenerative Capacity after Stroke. J Neuroimmune Pharmacol 11, 708–720 (2016). https://doi.org/10.1007/s11481-016-9694-5

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