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Background and Purpose: Endogenous Granulocyte-Colony Stimulating Factor (G-CSF) may have a protective effect through enrolling stem cells during the acute phases ofischemic stroke.In human beings, acute ischemic stroke induces secretion of G-CSF but the relationship between concentration of endogenous G-CSF and prognosis has not been evaluated before.Our aim was to establish whether higher plasma levels of endogenous G-CSF confer a better outcome (a possible neuroprotective effect).Methods: A total of 75 patients with acute ischemic stroke with onset within 2 days were included in the study and matched for age, sex, and other risk factors.Patients were followed up for 1 year and seen on three occasions including day 1, 3 months and 12 months.On admission plasma G-CSF concentration and inflammatory markers were measured and NIHSS and mRS scores were recorded.At follow up the severity scores were re-evaluated.Improvements in NIHSS and mRS scores and their relation to G-CSF concentration was our primary outcome.Results: According to the NIHSS and mRS scoring systems, serum G-CSF concentrations onadmission are the strongest prognostic indictor, compared with other inflammatory biomarkers.It positively correlates with the severity of stroke patients according to NIHSS scores on day 1, 3 months and 6 months after the event (P=4.4±10-5, 1.5±10-5 and 1.5±10-4, respectively).In particular, a serum level of G-CSF greater than 18.4μg/L can successfully predict a poor neurological recovery following moderate to severe major stroke (NIHSS≥8 or mRS≥4).Conclusions: The level of endogenous G-CSF failed to demonstrate a neuroprotective effect, but was shown to be a powerful predictor of severity and outcome following moderate to severe ischemic stroke.