Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Meta-Analysis
. 2010 May;30(5):961-8.
doi: 10.1038/jcbfm.2009.267. Epub 2009 Dec 30.

A systematic review and meta-analysis of erythropoietin in experimental stroke

Mikael Jerndal  1 , Kalle Forsberg, Emily S Sena, Malcolm R Macleod, Victoria E O'Collins, Thomas Linden, Michael Nilsson, David W Howells
Affiliations
Meta-Analysis

A systematic review and meta-analysis of erythropoietin in experimental stroke

Mikael Jerndal et al. J Cereb Blood Flow Metab. 2010 May.

Abstract

Erythropoietin (EPO) has shown promise as a neuroprotectant in animal models of ischemic stroke. EPO is thought not only to protect neurons from cell death, but also to promote regeneration after stroke. Here, we report a systematic review and meta-analysis of the efficacy of EPO in animal models of focal cerebral ischemia. Primary outcomes were infarct size and neurobehavioral outcome. Nineteen studies involving 346 animals for infarct size and 425 animals for neurobehavioral outcome met our inclusion criteria. Erythropoietin improved infarct size by 30.0% (95% CI: 21.3 to 38.8) and neurobehavioral outcome by 39.8% (33.7 to 45.9). Studies that randomized to treatment group or that blinded assessment of outcome showed lower efficacy. Erythropoietin was tested in animals with hypertension in no studies reporting infarct size and in 7.5% of the animals reporting neurobehavioral outcome. These findings show efficacy for EPO in experimental stroke, but when the impact of common sources of bias are considered, this efficacy falls, suggesting we may be overestimating its potential benefit. As common human co-morbidities may reduce therapeutic efficacy, broader testing to delineate the range of circumstances in which EPO works best would be beneficial.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Effect on the estimate of efficacy for infarct volume of (A) type of delivery, (B) method of artery occlusion, and for neurobehavioral outcome of (C) type of delivery, (D) method of artery occlusion, and (E) model of ischemia, P<0.003. The shaded gray bar represents the 95% confidence limits of the global estimate. The vertical error bars represent the 95% confidence intervals for the individual estimates. The width of each bar reflects the log of the number of animals contributing to that comparison.
Figure 2
Figure 2
Effect on the estimate of efficacy for infarct volume of (A) random allocation to treatment or control group, and for neurobehavioral outcome of (B) blinded assessment of outcome, P<0.003.
Figure 3
Figure 3
Effect on the estimate of efficacy of quality score (1=worst, 11=best) for (A) infarct volume and (B) neurobehavioral outcome, P<0.003.
See this image and copyright information in PMC

References

    1. Aluclu MU, Acar A, Guzel A, Bahceci S, Yaldiz M. Evaluation of erythroprotein effects on cerebral ischemia in rats. Neuroendocrinol Lett. 2007;28:170–174. - PubMed
    1. Belayev L, Khoutorova L, Zhao KL, Davidoff AW, Moore AF, Cramer SC. A novel neurotrophic therapeutic strategy for experimental stroke. Brain Res. 2009;1280:117–123. - PubMed
    1. Belayev L, Khoutorova L, Zhao W, Vigdorchik A, Belayev A, Busto R, Magal E, Ginsberg MD. Neuroprotective effect of darbepoetin alfa, a novel recombinant erythropoietic protein, in focal cerebral ischemia in rats. Stroke. 2005;36:1071–1076. - PubMed
    1. Bernaudin M, Marti HH, Roussel S, Divoux D, Nouvelot A, Mackenzie ET, Petit E. A potential role for erythropoietin in focal permanent cerebral ischemia in mice. J Cereb Blood Flow Metab. 1999;19:643–651. - PubMed
    1. Brines M, Cerami A. Erythropoietin-mediated tissue protection: reducing collateral damage from the primary injury response. J Intern Med. 2008;264:405–432. - PubMed

Publication types