title: GGF2 (Nrg1-β3) treatment enhances NG2+ cell response and improves functional recovery after spinal cord injury.
abstract: The adult spinal cord contains a pool of endogenous glial precursor cells, which spontaneously respond to spinal cord injury (SCI) with increased proliferation. These include oligodendrocyte precursor cells that express the NG2 proteoglycan and can differentiate into mature oligodendrocytes. Thus, a potential approach for SCI treatment is to enhance the proliferation and differentiation of these cells to yield more functional mature glia and improve remyelination of surviving axons. We previously reported that soluble glial growth factor 2 (GGF2)- and basic fibroblast growth factor 2 (FGF2)-stimulated growth of NG2(+) cells purified from injured spinal cord in primary culture. This study examines the effects of systemic administration of GGF2 and/or FGF2 after standardized contusive SCI in vivo in both rat and mouse models. In Sprague-Dawley rats, 1 week of GGF2 administration, beginning 24 h after injury, enhanced NG2(+) cell proliferation, oligodendrogenesis, chronic white matter at the injury epicenter, and recovery of hind limb function. In 2',3'-cyclic-nucleotide 3'-phosphodiesterase-enhanced green fluorescent protein mice, GGF2 treatment resulted in increased oligodendrogenesis and improved functional recovery, as well as elevated expression of the stem cell transcription factor Sox2 by oligodendrocyte lineage cells. Although oligodendrocyte number was increased chronically after SCI in GGF2-treated mice, no evidence of increased white matter was detected. However, GGF2 treatment significantly increased levels of P0 protein-containing peripheral myelin, produced by Schwann cells that infiltrate the injured spinal cord. Our results suggest that GGF2 may have therapeutic potential for SCI by enhancing endogenous recovery processes in a clinically relevant time frame.
authors: Department of Neuroscience, Georgetown University, Washington, District of Columbia 20057, USA.
authors: Matthew T
authors: MT
authors: Whittaker
authors: Laila J
authors: LJ
authors: Zai
authors: Hyun Joon
authors: HJ
authors: Lee
authors: Ahdeah
authors: A
authors: Pajoohesh-Ganji
authors: Junfang
authors: J
authors: Wu
authors: April
authors: A
authors: Sharp
authors: Ransom
authors: R
authors: Wyse
authors: Jean R
authors: JR
authors: Wrathall
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D005260:Female; D006133:Growth Substances / Q000096:biosynthesis / Q000502:physiology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009413:Nerve Fibers, Myelinated / Q000473:pathology / Q000502:physiology; D009416:Nerve Regeneration / Q000187:drug effects* / Q000502:physiology; D020890:Neuregulin-1 / Q000096:biosynthesis / Q000494:pharmacology / Q000502:physiology*; D009836:Oligodendroglia / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology; D020127:Recovery of Function / Q000187:drug effects / Q000235:genetics; D012583:Schwann Cells / Q000187:drug effects / Q000502:physiology; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D013234:Stem Cells / Q000187:drug effects / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics
chemical_list: D006133:Growth Substances; C094131:NRG1 protein, human; D020890:Neuregulin-1; D011994:Recombinant Proteins