Meta-Analysis of the Efficacy of Granulocyte-Colony Stimulating Factor in Animal Models of Focal Cerebral Ischemia

Minnerup J, Heidrich J, Wellmann J, Rogalewski A, Schneider A, Schäbitz W-R. Meta-Analysis of the Efficacy of Granulocyte-Colony Stimulating Factor in Animal Models of Focal Cerebral Ischemia. Stroke. 2008;39(6):1855-1861.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% (PPP=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