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 24 h 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 12 h 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 24 h.

Glioblastoma-synthesized G-CSF and GM-CSF contribute to growth and immunosuppression: Potential therapeutic benefit from dapsone, fenofibrate, and ribavirin

“…Serum G-CSF is acutely elevated in experimental animal closed head trauma and in humans in the emergency room after traumatic brain injury, 23 findings confirmed in studies in humans where timing of G(M)-CSF peak in plasma parallels peak elevation at the cerebral wound site during the first days following brain injury. 24,25 Post-traumatic hypoxia in patients with closed head trauma increases GM-CSF in the cerebrospinal fluid.…”

Blood Biomarkers for Evaluation of Perinatal Encephalopathy

“…Because neuroinflammation is such a prominent feature of traumatic brain injury, cytokines have been investigated as potential biomarkers. Cytokines play both harmful and curative roles in traumatic brain injury, readily cross the blood-brain barrier and may relay important information on the severity and prognosis of injury (Banks et al, 2016 ). High sensitivity C-reactive protein is a sensitive marker of inflammation and tissue injury whose concentration increases rapidly in brain tissue following hypoxia-ischemia.…”

Blood biomarkers for evaluation of perinatal encephalopathy: state of the art

“…G-CSF is elevated 2 h after controlled cortical injury, but not at later time points in mice, which may make it useful in determining the timing of injury (Dohi et al, 2014). Plasma G-CSF levels correlate with neuroinflammation in the same mouse models (Dohi et al, 2014) and in human studies where they correlate with time since injury and total severity of injury (Banks et al, 2016). In a neonatal rat HIE model treatment with G-CSF has been shown to attenuate long term brain damage (Fathali et al, 2010).…”

“…G-CSF has neuroprotective properties after peripheral administration and is protective against carbon monoxide toxicity and ischemia (Banks et al, 2016). Serum levels of G-CSF correlate with severity of stroke (Yu et al, 2012) and are diagnostic for gliomas (Yildiz et al, 2011).…”

“…Cytokines play both harmful and curative roles in traumatic brain injury, readily cross the blood-brain barrier and may relay important information on the severity and prognosis of injury (Banks et al, 2016). High sensitivity C-reactive protein is a sensitive marker of inflammation and tissue injury whose concentration increases rapidly in brain tissue following hypoxia-ischemia.…”