The comparative effects of recombinant human erythropoietin and darbepoetin-alpha on cerebral vasospasm following experimental subarachnoid hemorrhage in the rabbit

• Published in: Acta neurochirurgica Vol. 156; no. 5; pp. 951 - 962
• Main Authors: Kertmen, Hayri, Gürer, Bora, Yilmaz, Erdal Resit, Arikok, Ata Türker, Kanat, Mehmet Ali, Ergüder, Berrin Imge, Sekerci, Zeki
• Format: Journal Article
• Language: English
• Published: Vienna Springer Vienna 01.05.2014; Springer Nature B.V
• Subjects: Animals; Basilar Artery - drug effects; Basilar Artery - pathology; Darbepoetin alfa; Epoetin Alfa; Erythropoietin - analogs & derivatives; Erythropoietin - pharmacology; Experimental Research - Vascular; Hematinics - pharmacology; Hippocampus - drug effects; Hippocampus - pathology; Humans; Interventional Radiology; Male; Medicine; Medicine & Public Health; Minimally Invasive Surgery; Neurology; Neuroprotective Agents - pharmacology; Neuroradiology; Neurosurgery; Rabbits; Recombinant Proteins - pharmacology; Subarachnoid Hemorrhage - complications; Subarachnoid Hemorrhage - pathology; Surgical Orthopedics; Vasoconstriction - drug effects; Vasospasm, Intracranial - etiology; Vasospasm, Intracranial - pathology; Vasospasm, Intracranial - prevention & control; Rabbit; Vasospasm; Darbepoetin alpha; Erythropoietin; Subarachnoid hemorrhage
• ISSN: 0001-6268; 0942-0940
• DOI: 10.1007/s00701-014-2008-x

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.