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Submitted on October 9, 2007
From the Department of Neurology (J.M., A.R., W.-R.S.), and the Institute of Epidemiology and Social Medicine (J.H., J.W.), University of Münster, Münster, and Sygnis Bioscience (A.S.), Heidelberg, Germany. * To whom correspondence should be addressed. E-mail: minnerup{at}uni-muenster.de
or heidricj{at}uni-muenster.de.
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-µg/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.
Accepted on October 15, 2007
Meta-Analysis of the Efficacy of Granulocyte-Colony Stimulating Factor in Animal Models of Focal Cerebral Ischemia
Jens Minnerup MD*;
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