title: Granulocyte colony-stimulating factor promotes behavioral recovery in a mouse model of traumatic brain injury.
abstract: Hematopoietic growth factors such as granulocyte colony-stimulating factor (G-CSF) represent a novel approach for treatment of traumatic brain injury (TBI). After mild controlled cortical impact (CCI), mice were treated with G-CSF (100 μg/kg) for 3 consecutive days. The primary behavioral endpoint was performance on the radial arm water maze (RAWM), assessed 7 and 14 days after CCI. Secondary endpoints included 1) motor performance on a rotating cylinder (rotarod), 2) measurement of microglial and astroglial response, 3) hippocampal neurogenesis, and 4) measures of neurotrophic factors (brain-derived neurotrophic factor [BDNF] and glial cell line-derived neurotrophic factor [GDNF]) and cytokines in brain homogenates. G-CSF-treated animals performed significantly better than vehicle-treated mice in the RAWM at 1 and 2 weeks but not on the rotarod. Cellular changes found in the G-CSF group included increased hippocampal neurogenesis as well as astrocytosis and microgliosis in both the striatum and the hippocampus. Neurotrophic factors GDNF and BDNF, elaborated by activated microglia and astrocytes, were increased in G-CSF-treated mice. These factors along with G-CSF itself are known to promote hippocampal neurogenesis and inhibit apoptosis and likely contributed to improvement in the hippocampal-dependent learning task. Six cytokines that were modulated by G-CSF treatment following CCI were elevated on day 3, but only one of them remained altered by day 7, and all of them were no different from vehicle controls by day 14. The pro- and anti-inflammatory cytokines modulated by G-CSF administration interact in a complex and incompletely understood network involving both damage and recovery processes, underscoring the dual role of inflammation after TBI.
authors.affiliation: James Haley Veterans Administration Research Service, Tampa, Florida.|Department of Neurology, University of South Florida, Tampa, Florida.
authors.forename: Shijie
authors.initials: S
authors.lastname: Song
authors.affiliation: James Haley Veterans Administration Research Service, Tampa, Florida.|Department of Neurosurgery and Brain Repair, University of South Florida, Tampa, Florida.
authors.forename: Xiaoyuan
authors.initials: X
authors.lastname: Kong
authors.affiliation: Department of Neurosurgery and Brain Repair, University of South Florida, Tampa, Florida.
authors.forename: Sandra
authors.initials: S
authors.lastname: Acosta
authors.affiliation: James Haley Veterans Administration Research Service, Tampa, Florida.|Department of Neurosurgery and Brain Repair, University of South Florida, Tampa, Florida.
authors.forename: Vasyl
authors.initials: V
authors.lastname: Sava
authors.affiliation: Department of Neurology, University of South Florida, Tampa, Florida.
authors.forename: Cesar
authors.initials: C
authors.lastname: Borlongan
authors.affiliation: James Haley Veterans Administration Research Service, Tampa, Florida.|Department of Neurosurgery and Brain Repair, University of South Florida, Tampa, Florida.
authors.forename: Juan
authors.initials: J
authors.lastname: Sanchez-Ramos
mesh_terms: D000818:Animals; D000070642:Brain Injuries, Traumatic / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D020127:Recovery of Function / Q000187:drug effects* / Q000502:physiology
chemical_list: D016179:Granulocyte Colony-Stimulating Factor
keywords: astrocytosis; brain repair; cytokines; microgliosis; neurogenesis; neurotrophic factors; radial arm water maze
references.citation: Neuroscience. 2009 Sep 29;163(1):55-72
references.pmid: 19500657
references.citation: NeuroRx. 2005 Jul;2(3):410-22
references.pmid: 16389305
references.citation: Brain Res. 2006 Feb 16;1073-1074:190-201
references.pmid: 16423324
references.citation: Curr Opin Hematol. 1998 May;5(3):221-5
references.pmid: 9664164
references.citation: Stroke. 2003 Mar;34(3):745-51
references.pmid: 12624302
references.citation: Exp Neurol. 2005 Nov;196(1):87-95
references.pmid: 16112112
references.citation: J Cereb Blood Flow Metab. 2003 Jun;23(6):748-55
references.pmid: 12796723
references.citation: PLoS One. 2014;9(3):e90953
references.pmid: 24621603
references.citation: J Neurosci Res. 2014 Aug;92(8):975-80
references.pmid: 24664800
references.citation: Shock. 2001 Sep;16(3):165-77
references.pmid: 11531017
references.citation: Stroke. 2006 Apr;37(4):1123-8
references.pmid: 16514095
references.citation: Biochem Biophys Res Commun. 2013 May 17;434(4):779-84
references.pmid: 23603362
references.citation: Trends Pharmacol Sci. 2007 Apr;28(4):157-61
references.pmid: 17350693
references.citation: CMAJ. 2006 Mar 28;174(7):927-33
references.pmid: 16517764
references.citation: Cell. 2001 Feb 23;104(4):487-501
references.pmid: 11239407
references.citation: Hippocampus. 2002;12(5):578-84
references.pmid: 12440573
references.citation: Nature. 2001 Mar 15;410(6826):372-6
references.pmid: 11268214
references.citation: Stroke. 2010 Nov;41(11):2545-51
references.pmid: 20947859
references.citation: Nat Protoc. 2006;1(2):848-58
references.pmid: 17406317
references.citation: Exp Neurol. 2007 Apr;204(2):569-73
references.pmid: 17307165
references.citation: Cell Cycle. 2005 Dec;4(12):1753-7
references.pmid: 16258290
references.citation: J Clin Invest. 2005 Aug;115(8):2083-98
references.pmid: 16007267
references.citation: Stem Cells Int. 2013;2013:205878
references.pmid: 23554817
references.citation: J Neurosci. 1999 Mar 1;19(5):1708-16
references.pmid: 10024357
references.citation: J Alzheimers Dis. 2010;21(2):507-18
references.pmid: 20555144
references.citation: J Immunol. 1995 Dec 15;155(12):5769-76
references.pmid: 7499865
references.citation: Cell Tissue Res. 2007 Sep;329(3):409-20
references.pmid: 17541643
references.citation: Brain Res. 2009 Sep 1;1287:157-63
references.pmid: 19573519
references.citation: Neurol Res. 2010 Dec;32(10):1041-9
references.pmid: 20810026
references.citation: Exp Neurol. 1999 Aug;158(2):351-65
references.pmid: 10415142
references.citation: J Cereb Blood Flow Metab. 2010 Apr;30(4):769-82
references.pmid: 20029451
references.citation: Eur J Pharmacol. 2003 Jan 5;458(3):327-8
references.pmid: 12504790