Skip to main content
Erschienen in: Acta Neurochirurgica 6/2012

01.06.2012 | Experimental Research

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

verfasst von: Erdal Resit Yilmaz, Hayri Kertmen, Habibullah Dolgun, Bora Gürer, Ahmet Metin Sanli, Mehmet Ali Kanat, Ata Türker Arikok, Seda Yilmaz Bahsi, Berrin Imge Ergüder, Zeki Sekerci

Erschienen in: Acta Neurochirurgica | Ausgabe 6/2012

Einloggen, um Zugang zu erhalten

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.
Literatur
1.
Zurück zum Zitat Ates E, Yalcin AU, Yilmaz S, Koken T, Tokyol C (2005) Protective effect of erythropoietin on renal ischemia and reperfusion injury. ANZ J Surg 75:1100–1105PubMedCrossRef Ates E, Yalcin AU, Yilmaz S, Koken T, Tokyol C (2005) Protective effect of erythropoietin on renal ischemia and reperfusion injury. ANZ J Surg 75:1100–1105PubMedCrossRef
2.
Zurück zum Zitat Azbill RD, Mu X, Bruce-Keller AJ, Mattson MP, Springer JE (1997) Impaired mitochondrial function, oxidative stress and altered antioxidant enzyme activities following traumatic spinal cord injury. Brain Res 765:283–290PubMedCrossRef Azbill RD, Mu X, Bruce-Keller AJ, Mattson MP, Springer JE (1997) Impaired mitochondrial function, oxidative stress and altered antioxidant enzyme activities following traumatic spinal cord injury. Brain Res 765:283–290PubMedCrossRef
3.
Zurück zum Zitat Banks WA, Jumbe NL, Farrell CL, Niehoff ML, Heatherington AC (2004) Passage of erythropoietic agents across the blood–brain barrier: a comparison of human and murine erythropoietin and the analog darbepoetin alfa. Eur J Pharmacol 505:93–101PubMedCrossRef Banks WA, Jumbe NL, Farrell CL, Niehoff ML, Heatherington AC (2004) Passage of erythropoietic agents across the blood–brain barrier: a comparison of human and murine erythropoietin and the analog darbepoetin alfa. Eur J Pharmacol 505:93–101PubMedCrossRef
4.
Zurück zum Zitat Belayev L, Khoutorova L, Zhao W, Vigdorchik A, Belayev A, Busto R, Magal E, Ginsberg MD (2005) Neuroprotective effect of darbepoetin alfa, a novel recombinant erythropoietic protein, in focal cerebral ischemia in rats. Stroke 36:1071–1076PubMedCrossRef Belayev L, Khoutorova L, Zhao W, Vigdorchik A, Belayev A, Busto R, Magal E, Ginsberg MD (2005) Neuroprotective effect of darbepoetin alfa, a novel recombinant erythropoietic protein, in focal cerebral ischemia in rats. Stroke 36:1071–1076PubMedCrossRef
5.
Zurück zum Zitat Calvillo L, Latini R, Kajstura J, Leri A, Anversa P, Ghezzi P, Salio M, Cerami A, Brines M (2005) Recombinant human erythropoietin protects the myocardium from ischemia-reperfusion injury and promotes beneficial remodeling. Proc Natl Acad Sci USA 100:4802–4806CrossRef Calvillo L, Latini R, Kajstura J, Leri A, Anversa P, Ghezzi P, Salio M, Cerami A, Brines M (2005) Recombinant human erythropoietin protects the myocardium from ischemia-reperfusion injury and promotes beneficial remodeling. Proc Natl Acad Sci USA 100:4802–4806CrossRef
6.
Zurück zum Zitat Celik M, Gokmen N, Erbayraktar S, Akhisaroglu M, Konakc S, Ulukus C, Genc S, Genc K, Sagiroglu E, Cerami A, Brines M (2002) Erythropoietin prevents motor neuron apoptosis and neurologic disability in experimental spinal cord ischemic injury. Proc Natl Acad Sci USA 99:2258–2263PubMedCrossRef Celik M, Gokmen N, Erbayraktar S, Akhisaroglu M, Konakc S, Ulukus C, Genc S, Genc K, Sagiroglu E, Cerami A, Brines M (2002) Erythropoietin prevents motor neuron apoptosis and neurologic disability in experimental spinal cord ischemic injury. Proc Natl Acad Sci USA 99:2258–2263PubMedCrossRef
7.
Zurück zum Zitat Chronidou F, Apostolakis E, Papapostolou I, Grintzalis K, Georgiou CD, Koletsis EN, Karanikolas M, Papathanasopoulos P, Dougenis D (2009) Beneficial effect of the oxygen free radical scavenger amifostine (WR-2721) on spinal cord ischemia/reperfusion injury in rabbits. J Cardiothorac Surg 4:50PubMedCrossRef Chronidou F, Apostolakis E, Papapostolou I, Grintzalis K, Georgiou CD, Koletsis EN, Karanikolas M, Papathanasopoulos P, Dougenis D (2009) Beneficial effect of the oxygen free radical scavenger amifostine (WR-2721) on spinal cord ischemia/reperfusion injury in rabbits. J Cardiothorac Surg 4:50PubMedCrossRef
8.
Zurück zum Zitat Diaz-Ruiz A, Rios C, Duarte I, Correa D, Guizar-Sahagun G, Grijalva I, Madrazo I, Ibarra A (2000) Lipid peroxidation inhibition in spinal cord injury: cyclosporin-A vs methylprednisolone. Neuroreport 11:1765–1767PubMedCrossRef Diaz-Ruiz A, Rios C, Duarte I, Correa D, Guizar-Sahagun G, Grijalva I, Madrazo I, Ibarra A (2000) Lipid peroxidation inhibition in spinal cord injury: cyclosporin-A vs methylprednisolone. Neuroreport 11:1765–1767PubMedCrossRef
9.
Zurück zum Zitat Digicaylioglu M, Lipton SA (2001) Erythropoietin-mediated neuroprotection involves cross-talk between Jak2 and NF-kappaB signalling cascades. Nature 412:641–647PubMedCrossRef Digicaylioglu M, Lipton SA (2001) Erythropoietin-mediated neuroprotection involves cross-talk between Jak2 and NF-kappaB signalling cascades. Nature 412:641–647PubMedCrossRef
10.
Zurück zum Zitat Dolgun H, Sekerci Z, Turkoglu E, Kertmen H, Yilmaz ER, Anlar M, Erguder IB, Tuna H (2010) Neuroprotective effect of mesna (2-mercaptoethane sulfonate) against spinal cord ischemia/reperfusion injury in rabbits. J Clin Neurosci 17:486–489PubMedCrossRef Dolgun H, Sekerci Z, Turkoglu E, Kertmen H, Yilmaz ER, Anlar M, Erguder IB, Tuna H (2010) Neuroprotective effect of mesna (2-mercaptoethane sulfonate) against spinal cord ischemia/reperfusion injury in rabbits. J Clin Neurosci 17:486–489PubMedCrossRef
11.
Zurück zum Zitat Dumont RJ, Okonkwo DO, Verma S, Hurlbert RJ, Boulos PT, Ellegala DB, Dumont AS (2001) Acute spinal cord injury, part I: pathophysiologic mechanisms. Clin Neuropharmacol 24:254–264PubMedCrossRef Dumont RJ, Okonkwo DO, Verma S, Hurlbert RJ, Boulos PT, Ellegala DB, Dumont AS (2001) Acute spinal cord injury, part I: pathophysiologic mechanisms. Clin Neuropharmacol 24:254–264PubMedCrossRef
12.
Zurück zum Zitat Egrie JC, Browne JK (2001) Development and characterization of novel erythropoiesis stimulating protein (NESP). Br J Cancer 84:3–10PubMedCrossRef Egrie JC, Browne JK (2001) Development and characterization of novel erythropoiesis stimulating protein (NESP). Br J Cancer 84:3–10PubMedCrossRef
13.
Zurück zum Zitat Ehrenreich H, Hasselblatt M, Dembowski C, Cepek L, Lewczuk P, Stiefel M, Rustenbeck HH, Breiter N, Jacob S, Knerlich F, Bohn M, Poser W, Rüther E, Kochen M, Gefeller O, Gleiter C, Wessel TC, De Ryck M, Itri L, Prange H, Cerami A, Brines M, Sirén AL (2002) Erythropoietin therapy for acute stroke is both safe and beneficial. Mol Med 8:495–505PubMed Ehrenreich H, Hasselblatt M, Dembowski C, Cepek L, Lewczuk P, Stiefel M, Rustenbeck HH, Breiter N, Jacob S, Knerlich F, Bohn M, Poser W, Rüther E, Kochen M, Gefeller O, Gleiter C, Wessel TC, De Ryck M, Itri L, Prange H, Cerami A, Brines M, Sirén AL (2002) Erythropoietin therapy for acute stroke is both safe and beneficial. Mol Med 8:495–505PubMed
14.
Zurück zum Zitat Emery E, Aldana P, Bunge MB, Puckett W, Srinivasan A, Keane RW, Bethea J, Levi AD (1998) Apoptosis after traumatic human spinal cord injury. J Neurosurg 89:911–920PubMedCrossRef Emery E, Aldana P, Bunge MB, Puckett W, Srinivasan A, Keane RW, Bethea J, Levi AD (1998) Apoptosis after traumatic human spinal cord injury. J Neurosurg 89:911–920PubMedCrossRef
15.
Zurück zum Zitat Gao E, Boucher M, Chuprun JK, Zhou RH, Eckhart AD, Koch WJ (2007) Darbepoetin alfa, a long-acting erythropoietin analog, offers novel and delayed cardioprotection for the ischemic heart. Am J Physiol Heart Circ Physiol 293:H60–H68PubMedCrossRef Gao E, Boucher M, Chuprun JK, Zhou RH, Eckhart AD, Koch WJ (2007) Darbepoetin alfa, a long-acting erythropoietin analog, offers novel and delayed cardioprotection for the ischemic heart. Am J Physiol Heart Circ Physiol 293:H60–H68PubMedCrossRef
16.
Zurück zum Zitat Genovese T, Cuzzocrea S (2008) Role of free radicals and poly (ADP-ribose)polymerase-1 in the development of spinal cord injury: new potential therapeutic targets. Curr Med Chem 15:477–487PubMedCrossRef Genovese T, Cuzzocrea S (2008) Role of free radicals and poly (ADP-ribose)polymerase-1 in the development of spinal cord injury: new potential therapeutic targets. Curr Med Chem 15:477–487PubMedCrossRef
17.
Zurück zum Zitat Gunasekar PG, Kanthasamy AG, Borowitz JL, Isom GE (1995) NMDA receptor activation produces concurrent generation of nitric oxide and reactive oxygen species: implication for cell death. J Neurochem 65:2016–2021PubMedCrossRef Gunasekar PG, Kanthasamy AG, Borowitz JL, Isom GE (1995) NMDA receptor activation produces concurrent generation of nitric oxide and reactive oxygen species: implication for cell death. J Neurochem 65:2016–2021PubMedCrossRef
18.
Zurück zum Zitat Hagl C, Ergin MA, Galla JD, Lansman SL, McCullough JN, Spielvogel D, Sfeir P, Bodian CA, Griepp RB (2001) Neurologic outcome after ascending aorta-aortic arch operations: effect of brain protection technique in high-risk patients. J Thorac Cardiovasc Surg 121:1107–1121PubMedCrossRef Hagl C, Ergin MA, Galla JD, Lansman SL, McCullough JN, Spielvogel D, Sfeir P, Bodian CA, Griepp RB (2001) Neurologic outcome after ascending aorta-aortic arch operations: effect of brain protection technique in high-risk patients. J Thorac Cardiovasc Surg 121:1107–1121PubMedCrossRef
19.
Zurück zum Zitat Hayashi T, Sakuria M, Abe K, Sadahiro M, Tabayashi K, Itoyama Y (1998) Apoptosis of motor neurons with induction of caspases in the spinal cord after ischemia. Stroke 29:1007–1013PubMedCrossRef Hayashi T, Sakuria M, Abe K, Sadahiro M, Tabayashi K, Itoyama Y (1998) Apoptosis of motor neurons with induction of caspases in the spinal cord after ischemia. Stroke 29:1007–1013PubMedCrossRef
20.
Zurück zum Zitat Hearse DJ, Boli R (1992) Reperfusion induced injury: manifestations, mechanisms, and clinical relevance. Cardiovasc Res 26:101–108PubMedCrossRef Hearse DJ, Boli R (1992) Reperfusion induced injury: manifestations, mechanisms, and clinical relevance. Cardiovasc Res 26:101–108PubMedCrossRef
21.
Zurück zum Zitat Junk AK, Mammis A, Savitz SI, Singh M, Roth S, Malhotra S, Rosenbaum PS, Cerami A, Brines M, Rosenbaum DM (2002) Erythropoietin administration protects retinal neurons from acute ischemia-reperfusion injury. Proc Natl Acad Sci USA 99:10659–10664PubMedCrossRef Junk AK, Mammis A, Savitz SI, Singh M, Roth S, Malhotra S, Rosenbaum PS, Cerami A, Brines M, Rosenbaum DM (2002) Erythropoietin administration protects retinal neurons from acute ischemia-reperfusion injury. Proc Natl Acad Sci USA 99:10659–10664PubMedCrossRef
22.
Zurück zum Zitat Kaptanoglu E, Solaroglu I, Okutan O, Surucu HS, Akbiyik F, Beskonakli E (2004) Erythropoietin exerts neuroprotection after acute spinal cord injury in rats: effect on lipid peroxidation and early ultrastructural findings. Neurosurg Rev 27:113–120PubMedCrossRef Kaptanoglu E, Solaroglu I, Okutan O, Surucu HS, Akbiyik F, Beskonakli E (2004) Erythropoietin exerts neuroprotection after acute spinal cord injury in rats: effect on lipid peroxidation and early ultrastructural findings. Neurosurg Rev 27:113–120PubMedCrossRef
23.
Zurück zum Zitat Katircioglu SF, Ulus AT, Gökçe P, Sürücü S (2000) Iloprost protects the spinal cord during aortic cross-clamping in a canine model. J Cardiovasc Surg 41:89–93 Katircioglu SF, Ulus AT, Gökçe P, Sürücü S (2000) Iloprost protects the spinal cord during aortic cross-clamping in a canine model. J Cardiovasc Surg 41:89–93
24.
Zurück zum Zitat Keane RW, Kraydieh S, Lotocki G, Bethea JR, Krajewski S, Reed JC, Dietrich WD (2001) Apoptotic and anti-apoptotic mechanisms following spinal cord injury. J Neuropathol Exp Neurol 60:422–429PubMed Keane RW, Kraydieh S, Lotocki G, Bethea JR, Krajewski S, Reed JC, Dietrich WD (2001) Apoptotic and anti-apoptotic mechanisms following spinal cord injury. J Neuropathol Exp Neurol 60:422–429PubMed
25.
Zurück zum Zitat Klingmuller U (1997) The role of tyrosine phosphorylation in proliferation and maturation of erythroid progenitor cells signals emanating from the erythropoietin receptor. Eur J Biochem 249:637–647PubMedCrossRef Klingmuller U (1997) The role of tyrosine phosphorylation in proliferation and maturation of erythroid progenitor cells signals emanating from the erythropoietin receptor. Eur J Biochem 249:637–647PubMedCrossRef
26.
27.
28.
Zurück zum Zitat Li M, Ona VO, Chen M, Tenneti L, Zhang X, Stieg PE, Lipton SA, Friedlander RM (2000) Functional role and therapeutic implications of neuronal caspase-1 and −3 in a mouse model of traumatic spinal cord injury. Neuroscience 99:333–342PubMedCrossRef Li M, Ona VO, Chen M, Tenneti L, Zhang X, Stieg PE, Lipton SA, Friedlander RM (2000) Functional role and therapeutic implications of neuronal caspase-1 and −3 in a mouse model of traumatic spinal cord injury. Neuroscience 99:333–342PubMedCrossRef
29.
Zurück zum Zitat Li Y, Chopp M, Jiang N, Yao F, Zaloga C (1995) Temporal profile of in situ DNA fragmentation after transient middle cerebral artery occlusion in the rat. J Cereb Blood Flow Metab 15:389–397PubMedCrossRef Li Y, Chopp M, Jiang N, Yao F, Zaloga C (1995) Temporal profile of in situ DNA fragmentation after transient middle cerebral artery occlusion in the rat. J Cereb Blood Flow Metab 15:389–397PubMedCrossRef
30.
Zurück zum Zitat Lukacova N, Halat G, Chavko M, Marsala J (1996) Ischemia–reperfusion injury in the spinal cord of rabbits strongly enhances lipid peroxidation and modifies phospholipid profiles. Neurochem Res 21:869–873PubMedCrossRef Lukacova N, Halat G, Chavko M, Marsala J (1996) Ischemia–reperfusion injury in the spinal cord of rabbits strongly enhances lipid peroxidation and modifies phospholipid profiles. Neurochem Res 21:869–873PubMedCrossRef
31.
Zurück zum Zitat Markham A, Bryson HM (1995) Epoetin alfa. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic use in nonrenal applications. Drugs 49:232–254PubMedCrossRef Markham A, Bryson HM (1995) Epoetin alfa. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic use in nonrenal applications. Drugs 49:232–254PubMedCrossRef
32.
Zurück zum Zitat Marti HH, Bernaudin M, Petit E, Bauer C (2000) Neuroprotection and angiogenesis: dual role of erythropoietin in brain ischemia. News Physiol Sci 15:225–229PubMed Marti HH, Bernaudin M, Petit E, Bauer C (2000) Neuroprotection and angiogenesis: dual role of erythropoietin in brain ischemia. News Physiol Sci 15:225–229PubMed
33.
Zurück zum Zitat Parsa CJ, Matsumoto A, Kim J, Riel RU, Pascal LS, Walton GB, Thompson RB, Petrofski JA, Annex BH, Stamler JS, Koch WJ (2003) A novel protective effect of erythropoietin in the infarcted heart. J Clin Invest 112:999–1007PubMed Parsa CJ, Matsumoto A, Kim J, Riel RU, Pascal LS, Walton GB, Thompson RB, Petrofski JA, Annex BH, Stamler JS, Koch WJ (2003) A novel protective effect of erythropoietin in the infarcted heart. J Clin Invest 112:999–1007PubMed
34.
Zurück zum Zitat Patton J, Reeves T, Wallace J (2004) Effectiveness of darbepoetin alfa versus epoetin alfa in patients with chemotherapy-induced anemia treated in clinical practice. Oncologist 9:451–458PubMedCrossRef Patton J, Reeves T, Wallace J (2004) Effectiveness of darbepoetin alfa versus epoetin alfa in patients with chemotherapy-induced anemia treated in clinical practice. Oncologist 9:451–458PubMedCrossRef
35.
Zurück zum Zitat Qian H, Liu D (1997) The time course of malondialdehyde production following impact injury to rat spinal cord as measured by microdialysis and high pressure liquid chromatography. Neurochem Res 22:1231–1236PubMedCrossRef Qian H, Liu D (1997) The time course of malondialdehyde production following impact injury to rat spinal cord as measured by microdialysis and high pressure liquid chromatography. Neurochem Res 22:1231–1236PubMedCrossRef
36.
Zurück zum Zitat Sadamoto Y, Igase K, Sakanaka M, Sato K, Otsuka H, Sakaki S, Masuda S, Sasaki R (1998) Erythropoietin prevents place navigation disability and cortical infarction in rats with permanent occlusion of the middle cerebral artery. Biochem Biophys Res Commun 253:26–32PubMedCrossRef Sadamoto Y, Igase K, Sakanaka M, Sato K, Otsuka H, Sakaki S, Masuda S, Sasaki R (1998) Erythropoietin prevents place navigation disability and cortical infarction in rats with permanent occlusion of the middle cerebral artery. Biochem Biophys Res Commun 253:26–32PubMedCrossRef
37.
Zurück zum Zitat Sakanaka M, Wen TC, Matsuda S, Masuda S, Morishita E, Nagao M, Sasaki R (1995) In vivo evidence that erythropoietin protects neurons from ischemic damage. Proc Natl Acad Sci USA 95:4635–4640CrossRef Sakanaka M, Wen TC, Matsuda S, Masuda S, Morishita E, Nagao M, Sasaki R (1995) In vivo evidence that erythropoietin protects neurons from ischemic damage. Proc Natl Acad Sci USA 95:4635–4640CrossRef
38.
Zurück zum Zitat Sakurai M, Nagata T, Abe K, Horinouchi T, Itoyama Y, Tabayashi K (2003) Survival and death-promoting events after transient spinal cord ischemia in rabbits: induction of Akt and caspase3 in motor neurons. J Thorac Cardiovasc Surg 125:370–377PubMedCrossRef Sakurai M, Nagata T, Abe K, Horinouchi T, Itoyama Y, Tabayashi K (2003) Survival and death-promoting events after transient spinal cord ischemia in rabbits: induction of Akt and caspase3 in motor neurons. J Thorac Cardiovasc Surg 125:370–377PubMedCrossRef
39.
40.
Zurück zum Zitat Schwartzberg L, Shiffman R, Tomita D, Stolshek B, Rossi G, Adamson R (2003) A multicenter retrospective cohort study of practice patterns and clinical outcomes of the use of darbepoetin alfa and epoetin alfa for chemotherapy-induced anemia. Clin Ther 25:2781–2796PubMedCrossRef Schwartzberg L, Shiffman R, Tomita D, Stolshek B, Rossi G, Adamson R (2003) A multicenter retrospective cohort study of practice patterns and clinical outcomes of the use of darbepoetin alfa and epoetin alfa for chemotherapy-induced anemia. Clin Ther 25:2781–2796PubMedCrossRef
41.
Zurück zum Zitat Sepodes B, Maio R, Pinto R, Sharples E, Oliveira P, McDonald M, Yaqoob M, Thiemermann C, Mota-Filipe H (2006) Recombinant human erythropoietin protects the liver from hepatic ischemia-reperfusion injury in the rat. Transpl Int 19:919–926PubMedCrossRef Sepodes B, Maio R, Pinto R, Sharples E, Oliveira P, McDonald M, Yaqoob M, Thiemermann C, Mota-Filipe H (2006) Recombinant human erythropoietin protects the liver from hepatic ischemia-reperfusion injury in the rat. Transpl Int 19:919–926PubMedCrossRef
42.
Zurück zum Zitat Siren AL, Fratelli M, Brines M, Goemans C, Casagrande S, Lewczuk P, Keenan S, Gleiter C, Pasquali C, Capobianco A, Mennini T, Heumann R, Cerami A, Ehrenreich H, Ghezzi P (2001) Erythropoietin prevents neuronal apoptosis after cerebral ischemia and metabolic stress. Proc Natl Acad Sci USA 98:4044–4049PubMedCrossRef Siren AL, Fratelli M, Brines M, Goemans C, Casagrande S, Lewczuk P, Keenan S, Gleiter C, Pasquali C, Capobianco A, Mennini T, Heumann R, Cerami A, Ehrenreich H, Ghezzi P (2001) Erythropoietin prevents neuronal apoptosis after cerebral ischemia and metabolic stress. Proc Natl Acad Sci USA 98:4044–4049PubMedCrossRef
43.
Zurück zum Zitat Squadrito F, Altavilla D, Squadrito G, Campo GM, Arlotta M, Quartarone C, Saitta A, Caputi AP (1999) Recombinant human erythropoietin inhibits iNOS activity and reverts vascular dysfunction in splanchnic artery occlusion shock. Br J Pharmacol 127:482–428PubMedCrossRef Squadrito F, Altavilla D, Squadrito G, Campo GM, Arlotta M, Quartarone C, Saitta A, Caputi AP (1999) Recombinant human erythropoietin inhibits iNOS activity and reverts vascular dysfunction in splanchnic artery occlusion shock. Br J Pharmacol 127:482–428PubMedCrossRef
44.
Zurück zum Zitat Tramontano AF, Muniyappa R, Black AD, Blendea MC, Cohen I, Deng L, Sowers JR, Cutaia MV, El-Sherif N (2003) Erythropoietin protects cardiac myocytes from hypoxia-induced apoptosis through an Akt-dependent pathway. Biochem Biophys Res Commun 308:990–994PubMedCrossRef Tramontano AF, Muniyappa R, Black AD, Blendea MC, Cohen I, Deng L, Sowers JR, Cutaia MV, El-Sherif N (2003) Erythropoietin protects cardiac myocytes from hypoxia-induced apoptosis through an Akt-dependent pathway. Biochem Biophys Res Commun 308:990–994PubMedCrossRef
45.
Zurück zum Zitat Umeda Y, Mori Y, Takagi H, Iwata H, Matsuno Y, Hirose H (2003) Surgical outcome of abdominal aortic aneurysm repair in patients undergoing chronic hemodialysis. Heart Vessels 18:7–11PubMedCrossRef Umeda Y, Mori Y, Takagi H, Iwata H, Matsuno Y, Hirose H (2003) Surgical outcome of abdominal aortic aneurysm repair in patients undergoing chronic hemodialysis. Heart Vessels 18:7–11PubMedCrossRef
46.
Zurück zum Zitat Wright GL, Hanlon P, Amin K, Steenberger C, Murphy E, Arcasoy MO (2004) Erythropoietin receptor expression in adult rat cardiomyocytes is associated with an acute cardioprotective effect for recombinant erythropoietin during ischemia-reperfusion injury. FASEB J 18:1031–1033PubMed Wright GL, Hanlon P, Amin K, Steenberger C, Murphy E, Arcasoy MO (2004) Erythropoietin receptor expression in adult rat cardiomyocytes is associated with an acute cardioprotective effect for recombinant erythropoietin during ischemia-reperfusion injury. FASEB J 18:1031–1033PubMed
47.
Zurück zum Zitat Wu H, Ren B, Zhu J, Dong G, Xu B, Wang C, Zheng X, Jing H (2006) Pretreatment with recombined human erythropoietin attenuates ischemia-reperfusion-induced lung injury in rats. Eur J Cardiothorac Surg 29:902–907PubMedCrossRef Wu H, Ren B, Zhu J, Dong G, Xu B, Wang C, Zheng X, Jing H (2006) Pretreatment with recombined human erythropoietin attenuates ischemia-reperfusion-induced lung injury in rats. Eur J Cardiothorac Surg 29:902–907PubMedCrossRef
48.
Zurück zum Zitat Zivin JA, DeGirolami U (1980) Spinal cord infarction: a highly reproducible stroke model. Stroke 11:200–202PubMedCrossRef Zivin JA, DeGirolami U (1980) Spinal cord infarction: a highly reproducible stroke model. Stroke 11:200–202PubMedCrossRef
Metadaten
Titel
Effects of darbepoetin-alpha in spinal cord ischemia-reperfusion injury in the rabbit
verfasst von
Erdal Resit Yilmaz
Hayri Kertmen
Habibullah Dolgun
Bora Gürer
Ahmet Metin Sanli
Mehmet Ali Kanat
Ata Türker Arikok
Seda Yilmaz Bahsi
Berrin Imge Ergüder
Zeki Sekerci
Publikationsdatum
01.06.2012
Verlag
Springer Vienna
Erschienen in
Acta Neurochirurgica / Ausgabe 6/2012
Print ISSN: 0001-6268
Elektronische ISSN: 0942-0940
DOI
https://doi.org/10.1007/s00701-012-1298-0

Weitere Artikel der Ausgabe 6/2012

Acta Neurochirurgica 6/2012 Zur Ausgabe

Leitlinien kompakt für die Neurologie

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Sind Frauen die fähigeren Ärzte?

30.04.2024 Gendermedizin Nachrichten

Patienten, die von Ärztinnen behandelt werden, dürfen offenbar auf bessere Therapieergebnisse hoffen als Patienten von Ärzten. Besonders gilt das offenbar für weibliche Kranke, wie eine Studie zeigt.

Akuter Schwindel: Wann lohnt sich eine MRT?

28.04.2024 Schwindel Nachrichten

Akuter Schwindel stellt oft eine diagnostische Herausforderung dar. Wie nützlich dabei eine MRT ist, hat eine Studie aus Finnland untersucht. Immerhin einer von sechs Patienten wurde mit akutem ischämischem Schlaganfall diagnostiziert.

Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

25.04.2024 Hypotonie Nachrichten

Wenn unter einer medikamentösen Hochdrucktherapie der diastolische Blutdruck in den Keller geht, steigt das Risiko für schwere kardiovaskuläre Ereignisse: Darauf deutet eine Sekundäranalyse der SPRINT-Studie hin.

Frühe Alzheimertherapie lohnt sich

25.04.2024 AAN-Jahrestagung 2024 Nachrichten

Ist die Tau-Last noch gering, scheint der Vorteil von Lecanemab besonders groß zu sein. Und beginnen Erkrankte verzögert mit der Behandlung, erreichen sie nicht mehr die kognitive Leistung wie bei einem früheren Start. Darauf deuten neue Analysen der Phase-3-Studie Clarity AD.

Update Neurologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.