The comparative effects of recombinant human erythropoietin and darbepoetin-alpha on cerebral vasospasm following experimental subarachnoid hemorrhage in the rabbit.
BACKGROUND
Darbepoetin alpha is a hypersialylated analogue of erythropoietin effective for activating erythropoietin-receptors. This study investigated the vasodilator and neuroprotective effects of darbepoetin alpha on an experimental subarachnoid hemorrhage model and compared it with erythropoietin.


METHODS
Forty adult male New Zealand white rabbits were randomly divided into four groups of ten rabbits each: group 1 (control), group 2 (subarachnoid hemorrhage), group 3 (erythropoietin), and group 4 (darbepoetin alpha). Recombinant human erythropoietin was administered at a dose of 1,000 U/kg intraperitoneally after the induction of subarachnoid hemorrhage and continued every 8 h up to 72 h. Darbepoetin alpha was administered at a single intraperitoneal dose of 30 μg/kg. Animals were killed 72 h after subarachnoid hemorrhage. Basilar artery cross-sectional areas, arterial wall thicknesses, hippocampal degeneration scores and biochemical analyses were measured in all groups.


RESULTS
Both erythropoietin and darbepoetin alpha treatments were found to attenuate cerebral vasospasm and provide neuroprotection after subarachnoid hemorrhage in rabbits. Darbepoetin alpha revealed better morphometric and histopathological results than erythropoietin among experimental subarachnoid hemorrhage-induced vasospasm.


CONCLUSIONS
Our findings, for the first time, showed that darbepoetin alpha can prevent vasospasm and provides neuroprotection following experimental subarachnoid hemorrhage. Moreover, darbepoetin alpha showed better results when compared with erythropoietin.
Neurosurgery Clinic, Ministry of Health, Diskapi Yildirim Beyazit Education and Research Hospital, Ankara, Turkey.
Hayri
H
Kertmen
Bora
B
Gürer
Erdal Resit
ER
Yilmaz
Ata Türker
AT
Arikok
Mehmet Ali
MA
Kanat
Berrin Imge
BI
Ergüder
Zeki
Z
Sekerci
D000818:Animals; D001488:Basilar Artery / Q000187:drug effects* / Q000473:pathology; D000068256:Darbepoetin alfa; D000068817:Epoetin Alfa; D004921:Erythropoietin / Q000031:analogs & derivatives* / Q000494:pharmacology; D006397:Hematinics / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects* / Q000473:pathology; D006801:Humans; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D011817:Rabbits; D011994:Recombinant Proteins / Q000494:pharmacology; D013345:Subarachnoid Hemorrhage / Q000150:complications* / Q000473:pathology; D014661:Vasoconstriction / Q000187:drug effects*; D020301:Vasospasm, Intracranial / Q000209:etiology* / Q000473:pathology / Q000517:prevention & control
D006397:Hematinics; D018696:Neuroprotective Agents; D011994:Recombinant Proteins; D004921:Erythropoietin; D000068256:Darbepoetin alfa; D000068817:Epoetin Alfa