BACKGROUND AND PURPOSE: Recent reports have described the efficacy of the hematopoietic growth factor granulocyte-colony stimulating factor (G-CSF) in animal stroke models. Early clinical multicenter trials evaluating the effect of G-CSF in acute stroke and pilot clinical trials for the subacute phase are ongoing. To guide further development, a meta-analysis was performed to assess the effects of G-CSF on infarct size and sensorimotor deficits. METHODS: Using electronic and manual searches of the literature, we identified studies describing the efficacy of G-CSF in animal models of focal cerebral ischemia. Two reviewers independently selected studies and extracted data on study quality, G-CSF doses, time of administration, and outcome measured as infarct volume and/or sensorimotor deficit. Data from all studies were pooled by meta-regression analyses. RESULTS: Thirteen studies including 277 animals for infarct size calculation and 258 animals for assessment of sensorimotor deficit met the criteria for inclusion. Overall efficacy of G-CSF regarding infarct size reduction was 42%. Meta-regression analysis revealed a 0.8% (P<0.0001) decrease in infarct size per 1-mug/kg increase in G-CSF dose when applied within the first 6 hours and a 2.1% (P<0.0001) decrease when applied later than 6 hours after induction of ischemia with a significant (P=0.0004) greater infarct size reduction after delayed treatment. Sensorimotor deficits categorized into 3 subgroups improved between 24% and 40%. CONCLUSIONS: Our findings consolidate G-CSF as a drug that both reduces infarct size and enhances functional recovery. These effects are presumably dose dependent. In contrast to most other neuroprotectants, a beneficial outcome may also be achieved when treatment is delayed.
BACKGROUND AND PURPOSE: Recent reports have described the efficacy of the hematopoietic growth factor granulocyte-colony stimulating factor (G-CSF) in animal stroke models. Early clinical multicenter trials evaluating the effect of G-CSF in acute stroke and pilot clinical trials for the subacute phase are ongoing. To guide further development, a meta-analysis was performed to assess the effects of G-CSF on infarct size and sensorimotor deficits. METHODS: Using electronic and manual searches of the literature, we identified studies describing the efficacy of G-CSF in animal models of focal cerebral ischemia. Two reviewers independently selected studies and extracted data on study quality, G-CSF doses, time of administration, and outcome measured as infarct volume and/or sensorimotor deficit. Data from all studies were pooled by meta-regression analyses. RESULTS: Thirteen studies including 277 animals for infarct size calculation and 258 animals for assessment of sensorimotor deficit met the criteria for inclusion. Overall efficacy of G-CSF regarding infarct size reduction was 42%. Meta-regression analysis revealed a 0.8% (P<0.0001) decrease in infarct size per 1-mug/kg increase in G-CSF dose when applied within the first 6 hours and a 2.1% (P<0.0001) decrease when applied later than 6 hours after induction of ischemia with a significant (P=0.0004) greater infarct size reduction after delayed treatment. Sensorimotor deficits categorized into 3 subgroups improved between 24% and 40%. CONCLUSIONS: Our findings consolidate G-CSF as a drug that both reduces infarct size and enhances functional recovery. These effects are presumably dose dependent. In contrast to most other neuroprotectants, a beneficial outcome may also be achieved when treatment is delayed.
Authors: Victoria E O'Collins; Malcolm R Macleod; Susan F Cox; Leena Van Raay; Elena Aleksoska; Geoffrey A Donnan; David W Howells Journal: J Cereb Blood Flow Metab Date: 2010-10-27 Impact factor: 6.200
Authors: Sami Ridwan; Henrike Bauer; Katrin Frauenknecht; Kyra Hefti; Harald von Pein; Clemens J Sommer Journal: J Anat Date: 2014-01-05 Impact factor: 2.610
Authors: P L Martínez-Morales; A Revilla; I Ocaña; C González; P Sainz; D McGuire; I Liste Journal: Stem Cell Rev Rep Date: 2013-10 Impact factor: 5.739