title: Assessing blood granulocyte colony-stimulating factor as a potential biomarker of acute traumatic brain injury in mice and humans.
abstract: Previous work has found that serum G-CSF was acutely elevated in mice 24h but not one week after controlled cortical impact (CCI). The purpose of this study was to investigate whether blood G-CSF correlates with the elevated brain cytokines in mice after CCI and also if it correlates with traumatic brain injury (TBI) in humans. Here, we found in mice undergoing CCI, a procedure that induces direct injury to the brain, that serum G-CSF correlated directly or indirectly with several brain cytokines, indicating it is a useful marker for the neuroinflammation of TBI. A pilot study in humans (phase I, n=19) confirmed that plasma G-CSF is acutely elevated on day 1 (p<0.001) of TBI and has returned to baseline by one week. In a second human sample (phase II) (n=80), we found plasma G-CSF peaks about 12h after arriving in the emergency department (41.6+/-5.4 pg/ml). Aging was weakly associated (p<0.05) with a less robust elevation in serum G-CSF, but there was no difference with gender. ISS, a measure of total severity of injury, correlated with the degree of elevation in serum G-CSF (r=.419; p<0.05), but severity of head injury (via AIS) did not. The latter may have been because of the statistically narrow range of head injuries among our cases and the high number of cases diagnosed with closed head injury (a non-codable diagnosis). In conclusion, plasma G-CSF may be a useful biomarker of TBI, correlating with neuroinflammation in the animal model and in the human studies with time since injury and total severity of injury. As such, it may be useful in determining whether TBI has occurred within the last 24h.
authors.affiliation: Geriatrics Research Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA 98108, USA; Division of Gerontology and Geriatric Medicine, Department of Medicine, University of Washington, Seattle, WA 98104, USA. Electronic address: wabanks1@uw.edu.
authors.forename: William A
authors.initials: WA
authors.lastname: Banks
authors.affiliation: Geriatrics Research Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA 98108, USA; Division of Gerontology and Geriatric Medicine, Department of Medicine, University of Washington, Seattle, WA 98104, USA; Department of Emergency Medicine, The Jikei University School of Medicine, Tokyo, Japan. Electronic address: kdoppy@jikei.ac.jp.
authors.forename: Kenji
authors.initials: K
authors.lastname: Dohi
authors.affiliation: Geriatrics Research Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA 98108, USA; Division of Gerontology and Geriatric Medicine, Department of Medicine, University of Washington, Seattle, WA 98104, USA. Electronic address: nesnah@u.washington.edu.
authors.forename: Kim
authors.initials: K
authors.lastname: Hansen
authors.affiliation: Geriatrics Research Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA 98108, USA; Department of Biobehavioral Nursing & Health Systems, School of Nursing, University of Washington, Seattle, WA 98195, USA; Harborview Injury Prevention and Research Center, University of Washington, Seattle, WA 98104, USA. Electronic address: hilairet@uw.edu.
authors.forename: Hilaire J
authors.initials: HJ
authors.lastname: Thompson
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D015415:Biomarkers / Q000097:blood; D001812:Blood-Brain Barrier / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D000070642:Brain Injuries, Traumatic / Q000097:blood*; D016207:Cytokines / Q000097:blood; D004195:Disease Models, Animal; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000097:blood*; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D010865:Pilot Projects; D055815:Young Adult
chemical_list: D015415:Biomarkers; D016207:Cytokines; D016179:Granulocyte Colony-Stimulating Factor
keywords: Biomarker; Blood–brain barrier; G-CSF; Neuroinflammation; Traumatic brain injury