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Neurochem Res. 2007 Apr-May;32(4-5):783-97. Epub 2006 Dec 21.

Combination of growth factors enhances remyelination in a cuprizone-induced demyelination mouse model.

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  • 1Department of Neurobiology, Mental Retardation Research Center, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California-Los Angeles, 635 Charles E. Young Drive South, Los Angeles, CA 90095-7332, USA.

Abstract

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.

PMID:
17186374
[PubMed - indexed for MEDLINE]
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