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(Stroke. 2008;39:1855.)
© 2008 American Heart Association, Inc.

Original Contributions

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

Jens Minnerup, MD; Jan Heidrich, MD, MSc; Jürgen Wellmann, PhD; Andreas Rogalewski, MD; Armin Schneider, MD Wolf-Rüdiger Schäbitz, MD

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.

Correspondence to J. Minnerup, Universitätsklinikum Münster, Klinik und Poliklinik für Neurologie, Albert-Schweitzer-Straβe 33, 48149 Münster, Germany. E-mail minnerup{at}uni-muenster.de or J. Heidrich, Institute of Epidemiology and Social Medicine, University of Münster, Domagkstraβe 3, 48149 Münster, Germany. E-mail heidricj@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.

Key Words: strokehematopoietic cell growth factors • meta-analysis • animal models

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