Meta-analysis of the efficacy of granulocyte-colony stimulating factor in animal models of focal cerebral ischemia.

Abstract

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: Jens Minnerup, Jan Heidrich, Jürgen Wellmann, Andreas Rogalewski, Armin Schneider, Wolf-Rüdiger Schäbitz
• Journal: Stroke (Stroke) Vol. 39 Issue 6 Pg. 1855-61 (Jun 2008) ISSN: 1524-4628 [Electronic] United States
• PMID: 18403735 (Publication Type: Journal Article, Meta-Analysis)

Chemical References

• Granulocyte Colony-Stimulating Factor

Topics

• Animals
• Brain (blood supply, drug effects, physiopathology)
• Brain Ischemia (drug therapy)
• Cerebral Arteries (drug effects, metabolism, physiopathology)
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Drug Administration Schedule
• Granulocyte Colony-Stimulating Factor (pharmacology, therapeutic use)
• Movement Disorders (drug therapy, etiology, physiopathology)
• Neurologic Examination
• Predictive Value of Tests
• Recovery of Function (drug effects, physiology)
• Treatment Outcome