Neuroprotective effect of darbepoetin alfa, a novel recombinant erythropoietic protein, in focal cerebral ischemia in rats.
OBJECTIVE
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 microg/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.


CONCLUSIONS
Darbepoetin alfa confers behavioral and histological neuroprotection after focal ischemia in rats.
Belayev
Ludmila
L
Cerebral Vascular Disease Research Center, Department of Neurology, University of Miami School of Medicine, Miami, Fla 33101, USA. lbelayev@stroke.med.miami.edu
Khoutorova
Larissa
L
Zhao
Weizhao
W
Vigdorchik
Alexey
A
Belayev
Andrey
A
Busto
Raul
R
Magal
Ella
E
Ginsberg
Myron D
MD
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001929:Brain Edema / Q000188:drug therapy / Q000473:pathology; D002545:Brain Ischemia / Q000175:diagnosis / Q000188:drug therapy*; D000068256:Darbepoetin alfa; D004921:Erythropoietin / Q000031:analogs & derivatives* / Q000235:genetics / Q000627:therapeutic use*; D020244:Infarction, Middle Cerebral Artery / Q000473:pathology; D008297:Male; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000627:therapeutic use
D018696:Neuroprotective Agents; D011994:Recombinant Proteins; D004921:Erythropoietin; D000068256:Darbepoetin alfa