FGF-2-induced cell proliferation stimulates anatomical, neurophysiological and functional recovery from neonatal motor cortex injury

Authors

  • Marie-H. Monfils,

    1. Canadian Centre for Behavioural Neuroscience, University of Lethbridge, 4401 University Drive, Lethbridge, Alberta, Canada
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    • *

      Present address: Center for Neural Science, 4 Washington Place, Room 809, New York University, New York, NY, USA, 10003–6621.

  • Ira Driscoll,

    1. Canadian Centre for Behavioural Neuroscience, University of Lethbridge, 4401 University Drive, Lethbridge, Alberta, Canada
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  • Holly Kamitakahara,

    1. Canadian Centre for Behavioural Neuroscience, University of Lethbridge, 4401 University Drive, Lethbridge, Alberta, Canada
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  • Brett Wilson,

    1. Canadian Centre for Behavioural Neuroscience, University of Lethbridge, 4401 University Drive, Lethbridge, Alberta, Canada
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  • Corey Flynn,

    1. Behavioural Neuroscience Research Group, University of Calgary, 2500 University Drive, Alberta, Canada
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  • G. Campbell Teskey,

    1. Behavioural Neuroscience Research Group, University of Calgary, 2500 University Drive, Alberta, Canada
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  • Jeffrey A. Kleim,

    1. Canadian Centre for Behavioural Neuroscience, University of Lethbridge, 4401 University Drive, Lethbridge, Alberta, Canada
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  • Bryan Kolb

    1. Canadian Centre for Behavioural Neuroscience, University of Lethbridge, 4401 University Drive, Lethbridge, Alberta, Canada
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Dr Marie-H. Monfils, present address below.
E-mail: monfils@cns.nyu.edu

Abstract

Infant rats treated with basic fibroblast growth factor-2 (FGF-2) after postnatal day (P)10 motor cortical injury, show functional improvement in adulthood relative to those that do not receive FGF-2. In this study we used a combination of behavioural, immunohistochemical, electrophysiological, electron microscopic and teratological approaches to investigate possible mechanisms by which FGF-2 may influence functional recovery. We show that subcutaneous injections of FGF-2 following bilateral lesions to the motor cortex at P10 in the rat leads to filling of the lesion area with migrating neuroblasts and cycling cells. We assessed the functionality of this tissue in adulthood, and show that cells from the filled region spontaneously fire and form synapses. Behavioural analysis shows enhanced motor performance in the FGF-2-treated lesion rats in comparison to vehicle-treated lesion rats, and this improvement is reversed by removal of the tissue from the previously lesioned area or by blocking cortical regeneration by embryonic treatment with bromodeoxyuridine (BrdU). The results show that FGF-2 stimulates filling of the lesion cavity with cells after neonatal motor cortex lesions, that the new tissue has anatomical and physiological properties similar to control tissue, and that the filled region supports motor behaviour.

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