title: Effects of darbepoetin-α in spinal cord ischemia-reperfusion injury in the rabbit.
abstract: 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.
authors.affiliation: 1st Neurosurgery Clinic, Ministry of Health, Diskapi Yildirim Beyazit Education and Research Hospital, Ankara, Turkey.
authors.forename: Erdal Resit
authors.initials: ER
authors.lastname: Yilmaz
authors.forename: Hayri
authors.initials: H
authors.lastname: Kertmen
authors.forename: Habibullah
authors.initials: H
authors.lastname: Dolgun
authors.forename: Bora
authors.initials: B
authors.lastname: Gürer
authors.forename: Ahmet Metin
authors.initials: AM
authors.lastname: Sanli
authors.forename: Mehmet Ali
authors.initials: MA
authors.lastname: Kanat
authors.forename: Ata Türker
authors.initials: AT
authors.lastname: Arikok
authors.forename: Seda Yilmaz
authors.initials: SY
authors.lastname: Bahsi
authors.forename: Berrin Imge
authors.initials: BI
authors.lastname: Ergüder
authors.forename: Zeki
authors.initials: Z
authors.lastname: Sekerci
mesh_terms: D000740:Anemia / Q000188:drug therapy / Q000473:pathology; D000818:Animals; D000068256:Darbepoetin alfa; D004195:Disease Models, Animal; D004921:Erythropoietin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D006397:Hematinics / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D011817:Rabbits; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000503:physiopathology; D020760:Spinal Cord Ischemia / Q000188:drug therapy* / Q000503:physiopathology
chemical_list: D006397:Hematinics; D018696:Neuroprotective Agents; D004921:Erythropoietin; D000068256:Darbepoetin alfa