Systematic review and meta-analysis of the efficacy of basic fibroblast growth factor in experimental stroke

• Background Basic fibroblast growth factor (bFGF) has been shown to have a potent trophic effect on brain neurons, glia and endothelial cells in both in vitro and in vivo studies and is a candidate drug for treatment of ischemic stroke. Any decision to proceed to clinical trials should be based on an unbiased assessment of all available animal data. This assessment should evaluate the efficacy of the drug as well as the characteristics and limits to that efficacy. We use a systematic approach to assess the evidence for protective effects of bFGF in animal models of focal cerebral ischemia. Methods We have performed a systematic review and meta-analysis of studies describing the efficacy of bFGF in animal models of focal cerebral ischemia where outcome was measured as infarct size or neurological score. Study quality was scored against a quality checklist and certain study characteristics were looked at individually. A random effects model was used and the significance level was set to p<0.001 to allow for multiple comparisons. Results Systematic review identified 21 publications of which 20 report infarct size from 520 animals and 10 report neurological score from 223 animals. bFGF reduced infarct size by 25.7% (95% confidence interval 21.7-29.8%) and improved neurological score by 28.1% (23.0-33.2%). Efficacy was higher with intra-arterial administration which showed a reduction of infarct size by 57.6% (33.8-81.3%, p=9.8E-07). Overall study quality was moderate with a median quality score of 6/11, interquartile range 5-7. Studies that performed blinded assessment of outcome showed lesser efficacy on infarct size reduction than those who did not blind, 20.2% (12.2-28.1) compared to 29.4% (26.7-32.1%, p=0.00073). The use of animals with associated comorbidities was rare, with only 4.4% aged animals and no animals with diabetes or hypertension. Aged animals showed lower effect size with only 4.7% reduction of infarct size (-9.0-18.3%, p=1.0E-05). Conclusion Our study shows that bFGF-1 has efficacy in experimental ischemic stroke. The effect of study quality and bias limits the strength of this conclusion. Further research is needed to test the efficacy in animals with associated co morbidities.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Neurologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Neurology (hsv//eng)

NATURVETENSKAP  -- Data- och informationsvetenskap -- Bioinformatik (hsv//swe)

NATURAL SCIENCES  -- Computer and Information Sciences -- Bioinformatics (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Neurosciences (hsv//eng)

Nyckelord

stroke

experimental therapies

growth factors

animal studies

meta-analysis

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