Published Online
on March 24, 2005

A more recent version of this article appeared on May 1, 2005

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Submitted on November 24, 2004
Revised on January 5, 2005
Accepted on January 18, 2005

Neuroprotective Effect of Darbepoetin Alfa, a Novel Recombinant Erythropoietic Protein, in Focal Cerebral Ischemia in Rats

Ludmila Belayev MD^*; Larissa Khoutorova BS; Weizhao Zhao PhD; Alexey Vigdorchik MD; Andrey Belayev BS; Raul Busto BS; Ella Magal PhD; and Myron D. Ginsberg MD

From Cerebral Vascular Disease Research Center (L.B., L.K., W.Z., A.V., A.B., R.B., M.D.G.), Department of Neurology, University of Miami School of Medicine Miami, Fla; Amgen Inc (E.M.), Thousand Oaks, Calif.

^* To whom correspondence should be addressed. E-mail: lbelayev{at}stroke.med.miami.edu.

Background and Purpose--Darbepoetin alfa is a novel erythropoiesis-stimulating protein developed for treating anemia. In animal models, exogenous recombinant human erythropoietin has been reported to be beneficial in treating experimental cerebral ischemia. In this study, we determined whether darbepoetin alfa would protect in a rat model of transient focal cerebral ischemia.

Methods--Rats received 2-hour middle cerebral artery suture-occlusion. The drug (darbepoetin alfa, 10 µg/kg) or vehicle was administered intraperitoneally 2 hours after onset of middle cerebral artery occlusion. Animals were allowed to survive for 3 or 14 days. Behavioral tests were performed sequentially. Infarct volumes and brain swelling were determined.

Results--Darbepoetin alfa-treated rats showed improved neuroscores relative to vehicle-treated animals beginning within 1 hour of treatment and persisting throughout the 14-day survival period. Darbepoetin alfa significantly reduced corrected total (cortical + subcortical) infarct volume (56.3±20.6 and 110.8±6.8 mm³, respectively) and total infarct areas at multiple levels compared with vehicle in the 14-day survival group. Brain swelling was not affected by treatment.

Conclusion--Darbepoetin alfa confers behavioral and histological neuroprotection after focal ischemia in rats.

Key words: brain edema • cerebral ischemia • focal • middle cerebral artery occlusion • neuroprotection

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