Effects of darbepoetin-alpha in spinal cord ischemia-reperfusion injury in the rabbit

Background Darbepoetin-alpha (DA) is a novel erythropoiesis-stimulating agent developed for treating anemia. In animal models, recombinant human erythropoietin has been reported to be beneficial for neuroprotection. In this study, we determined whether DA would protect the spinal cord against ischem...

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Bibliographic Details
Published in:	Acta neurochirurgica Vol. 154; no. 6; pp. 1037 - 1044
Main Authors:	Yilmaz, Erdal Resit, Kertmen, Hayri, Dolgun, Habibullah, Gürer, Bora, Sanli, Ahmet Metin, Kanat, Mehmet Ali, Arikok, Ata Türker, Bahsi, Seda Yilmaz, Ergüder, Berrin Imge, Sekerci, Zeki
Format:	Journal Article
Language:	English
Published:	Vienna Springer Vienna 01-06-2012 Springer Nature B.V
Subjects:	Anemia Anemia - drug therapy Anemia - pathology Aneurysm Animal models Animals Aorta Apoptosis Caspase-3 Darbepoetin alfa Degeneration Disease Models, Animal Dopamine Drugs Erythropoietin - analogs & derivatives Erythropoietin - pharmacology Erythropoietin - therapeutic use Experimental Research Hematinics - pharmacology Hematinics - therapeutic use Interventional Radiology Ischemia Lipid peroxidation Male Malondialdehyde Medicine Medicine & Public Health methylprednisolone Minimally Invasive Surgery Neurology Neuroprotection Neuroprotective Agents - pharmacology Neuroprotective Agents - therapeutic use Neuroradiology Neurosurgery Occlusion Rabbits Renal artery Reperfusion Reperfusion Injury - drug therapy Reperfusion Injury - physiopathology Spinal cord Spinal cord injury Spinal Cord Ischemia - drug therapy Spinal Cord Ischemia - physiopathology Surgical Orthopedics Darbepoetin-alpha Neuroprotection Spinal cord Ischemia reperfusion
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Summary:	Background Darbepoetin-alpha (DA) is a novel erythropoiesis-stimulating agent developed for treating anemia. In animal models, recombinant human erythropoietin has been reported to be beneficial for neuroprotection. In this study, we determined whether DA would protect the spinal cord against ischemia-reperfusion injury in a rabbit model. Methods Forty rabbits were randomized into five groups of eight animals each: group 1 (sham), group 2 (ischemia), group 3 (vehicle), group 4 (30 mg/kg methylprednisolone), group 5 (30 μg/kg DA). Only laparotomy was performed in the sham group. In all the other groups, the spinal cord ischemia model was created by a 20-min occlusion of the aorta just caudal to renal artery with an aneurysm clip. The drugs were administered immediately after the clamp was removed. The animals were killed 24 h later. Spinal cord segments between L2 and L5 were harvested for analysis. Neurological evaluation was performed with the Tarlov scoring system just before the animals were killed. Level of tissue malondialdehyde was analyzed as a marker of lipid peroxidation and tissue caspase-3 activity as a marker of apoptosis. Also, histopathological evaluation of the tissues was performed. Results Both malondialdehyde and caspase-3 levels were significantly decreased by DA administration. Histopathological evaluation of the tissues also demonstrated decrease in neuronal degeneration and infiltration parameters after DA administration. In the DA group, neurological outcome scores were statistically significantly better compared with the ischemia and the vehicle groups. Conclusions Although further studies considering different dose regimens and time intervals are required, DA was shown to be at least as effective as methylprednisolone in spinal cord ischemia/reperfusion model.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 ObjectType-Article-2 ObjectType-Feature-1
ISSN:	0001-6268 0942-0940
DOI:	10.1007/s00701-012-1298-0