title: Granulocyte-macrophage colony-stimulating factor is neuroprotective in experimental traumatic brain injury.
abstract: Traumatic brain injury (TBI) is an international health concern with a complex pathogenesis resulting in major long-term neurological, neurocognitive, and neuropsychiatric outcomes. Although neuroinflammation has been identified as an important pathophysiological process resulting from TBI, the function of specific inflammatory mediators in the aftermath of TBI remains poorly understood. Granulocyte-macrophage colony-stimulating factor (GM-CSF) is an inflammatory cytokine that has been reported to have neuroprotective effects in various animal models of neurodegenerative disease that share pathological similarities with TBI. The importance of GM-CSF in TBI has yet to be studied, however. We examined the role of GM-CSF in TBI by comparing the effects of a lateral fluid percussion (LFP) injury or sham injury in GM-CSF gene deficient (GM-CSF(-/-)) versus wild-type (WT) mice. After a 3-month recovery interval, mice were assessed using neuroimaging and behavioral outcomes. All mice given a LFP injury displayed significant brain atrophy and behavioral impairments compared with those given sham-injuries; however, this was significantly worse in the GM-CSF(-/-) mice compared with the WT mice. GM-CSF(-/-) mice given LFP injury also had reduced astrogliosis compared with their WT counterparts. These novel findings indicate that the inflammatory mediator, GM-CSF, may have significant protective properties in the chronic sequelae of experimental TBI and suggest that further research investigating GM-CSF and its potential benefits in the injured brain is warranted.
authors.affiliation: 1 Department of Medicine (The Royal Melbourne Hospital), Melbourne Brain Centre, The University of Melbourne , Parkville, Victoria, Australia .
authors.forename: Sandy R
authors.initials: SR
authors.lastname: Shultz
authors.forename: Xin L
authors.initials: XL
authors.lastname: Tan
authors.forename: David K
authors.initials: DK
authors.lastname: Wright
authors.forename: Shijie J
authors.initials: SJ
authors.lastname: Liu
authors.forename: Bridgette D
authors.initials: BD
authors.lastname: Semple
authors.forename: Leigh
authors.initials: L
authors.lastname: Johnston
authors.forename: Nigel C
authors.initials: NC
authors.lastname: Jones
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Cook
authors.forename: John A
authors.initials: JA
authors.lastname: Hamilton
authors.forename: Terence J
authors.initials: TJ
authors.lastname: O'Brien
mesh_terms: D000818:Animals; D001930:Brain Injuries / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D005455:Fluorescent Antibody Technique; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism*; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout
chemical_list: D016178:Granulocyte-Macrophage Colony-Stimulating Factor