Neurochemical Research

, Volume 32, Issue 4–5, pp 783–797 | Cite as

Combination of Growth Factors Enhances Remyelination in a Cuprizone-induced Demyelination Mouse Model

  • Shalini Kumar
  • Juan Carlos Biancotti
  • Masahiro Yamaguchi
  • Jean de Vellis
Original Paper


Loss of oligodendrocytes (OLs) is often associated with demyelination. PDGF-AA, bFGF, NT3 and IGF-1 are known to regulate OL proliferation, survival and/or differentiation. Following cuprizone-induced demyelination in mice a combination of above four growth factors (GF) was intracranially injected to stimulate remyelination in vivo. Activation of cell signaling and transcription factors involved in cell proliferation, survival and differentiation was observed in response to GF. Increased cell proliferation and migration occurred in corpus callosum, lateral ventricles, rostral migratory stream and cerebri at 2–5 days post injection (dpi) of GF cocktail. The fate of these newly formed nestin or bromodeoxyuridine (BrdU) positive progenitors was traced to proteoglycan NG2 and glutathione transferase (GST) pi positive cells, early and mature OL lineage markers, respectively. Immunostaining for myelin showed the presence of more myelinated fibers in GF-injected brains at 21 dpi. Remyelination in response to GF was confirmed by electron microscopy. In conclusion, this combination of GF is a promising tool to consider for remyelination strategies.


Oligodendrocytes Proliferation Migration Differentiation Myelin Cuprizone Demyelination Remyelination 


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Copyright information

© Springer Science+Business Media, LLC 2006

Authors and Affiliations

  • Shalini Kumar
    • 1
  • Juan Carlos Biancotti
    • 1
  • Masahiro Yamaguchi
    • 2
  • Jean de Vellis
    • 1
  1. 1.Departments of Neurobiology and PsychiatryMental Retardation Research Center, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of CaliforniaLos AngelesUSA
  2. 2.Department of PhysiologyUniversity of TokyoTokyoJapan

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