- About this Journal
- Abstracting and Indexing
- Aims and Scope
- Article Processing Charges
- Articles in Press
- Author Guidelines
- Bibliographic Information
- Citations to this Journal
- Contact Information
- Editorial Board
- Editorial Workflow
- Free eTOC Alerts
- Publication Ethics
- Reviewers Acknowledgment
- Submit a Manuscript
- Subscription Information
- Table of Contents
Neurology Research International
Volume 2011 (2011), Article ID 453179, 8 pages
Erythropoietin: Recent Developments in the Treatment of Spinal Cord Injury
1Laboratory of Pharmacology, Department of Medicine, Surgery and Dentistry, University of Milan, Polo H. San Paolo, Via A. di Rudinì 8, 20142 Milan, Italy
2Clinical Pharmacology, IRCCS Humanitas, Via Manzoni 56, Rozzano, 20089 Milan, Italy
3Cerebrovascular Unit, IRCCS, Istituto Neurologico C Besta, Via Celoria 11, 20133 Milan, Italy
4Department of Medicine, Surgery and Dentistry, University of Milan, Polo H. San Paolo, Via A. di Rudinì 8, 20142 Milan, Italy
Received 24 February 2011; Accepted 9 May 2011
Academic Editor: Jeff Bronstein
Copyright © 2011 Stephana Carelli et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
- C. H. Tator, “Update on the pathophysiology and pathology of acute spinal cord injury,” Brain Pathology, vol. 5, no. 4, pp. 407–413, 1995.
- M. D. Norenberg, J. Smith, and A. Marcillo, “The pathology of human spinal cord injury: defining the problems,” Journal of Neurotrauma, vol. 21, no. 4, pp. 429–440, 2004.
- American Association of Neurological Surgeons, “Pharmacological therapy after acute cervical spinal cord injury,” Neurosurgery, vol. 50, no. 3, pp. S63–S72, 2002.
- M. Brines and A. Cerami, “Erythropoietin in spinal cord injury,” in Erythropoietin and the Nervous System: Novel Therapeutic Options for Neuroprotection, pp. 147–164, Springer, New York, NY, USA, 2006.
- C. Carnot and C. DeFlandre, “Sur l'activite hematopoietique du serum au cours de la regeneration due sang,” Comptes Rendue Hebdomadaires des Séances de Paris, vol. 143, pp. 432–435, 1906.
- E. Bonsdorf and E. Jalavisto, “A humoral mechanism in anoxic erythrocytosis,” Acta Physiologica Scandinavica, vol. 16, pp. 150–170, 1948.
- J. S. Powell, K. L. Berkner, R. V. Lebo, and J. W. Adamson, “Human erythropoietin gene: high level expression in stably transfected mammalian cells and chromosome localization,” Proceedings of the National Academy of Sciences of the United States of America, vol. 83, no. 17, pp. 6465–6469, 1986.
- C. Kasper, “Erythropoietin,” in The Cytokine Handbook, A. W. Thomson and M. T. Lotze, Eds., vol. 1, pp. 149–166, Elsevier, London, UK, 4th edition, 2003.
- W. Jelkmann, “Erythropoietin: structure, control of production, and function,” Physiological Reviews, vol. 72, no. 2, pp. 449–489, 1992.
- P.-H. Lai, R. Everett, and F.-F. Wang, “Structural characterization of human erythropoietin,” Journal of Biological Chemistry, vol. 261, no. 7, pp. 3116–3121, 1986.
- E. Goldwasser, C. K. H. Kung, and J. Eliason, “On the mechanism of erythropoietin induced differentiation. XIII. The role of sialic acid in erythropoietin action,” Journal of Biological Chemistry, vol. 249, no. 13, pp. 4202–4206, 1974.
- M. S. Dordal, F. F. Wang, and E. Goldwasser, “The role of carbohydrate in erythropoietin action,” Endocrinology, vol. 116, no. 6, pp. 2293–2299, 1985.
- J. C. Winkelmann, L. A. Penny, L. L. Deaven, B. G. Forget, and R. B. Jenkins, “The gene for the human erythropoietin receptor: analysis of the coding sequence and assignment to chromosome 19p,” Blood, vol. 76, no. 1, pp. 24–30, 1990.
- G. Grasso, A. Sfacteria, M. Passalacqua et al., “Erythropoietin and erythropoietin receptor expression after experimental spinal cord injury encourages therapy by exogenous erythropoietin,” Neurosurgery, vol. 56, no. 4, pp. 821–826, 2005.
- A. Sönmez, B. Kabakçi, E. Vardar et al., “Erythropoietin attenuates neuronal injury and potentiates the expression of pCREB in anterior horn after transient spinal cord ischemia in rats,” Surgical Neurology, vol. 68, no. 3, pp. 297–303, 2007.
- K. P. Conrad, D. F. Benyo, A. Westerhausen-Larsen, and T. M. Miles, “Expression of erythropoietin by the human placenta,” FASEB Journal, vol. 10, no. 7, pp. 760–766, 1996.
- C. C. Tan, K. U. Eckardt, and P. J. Ratcliffe, “Organ distribution of erythropoietin messenger RNA in normal and uremic rats,” Kidney International, vol. 40, no. 1, pp. 69–76, 1991.
- M. Chikuma, S. Masuda, T. Kobayashi, M. Nagao, and R. Sasaki, “Tissue-specific regulation of erythropoietin production in the murine kidney, brain, and uterus,” American Journal of Physiology, vol. 279, no. 6, pp. E1242–E1248, 2000.
- B. B. Beleslin-Cokic, V. P. Cokic, X. Yu, B. B. Weksler, A. N. Schechter, and C. T. Noguchi, “Erythropoietin and hypoxia stimulate erythropoietin receptor and nitric oxide production by endothelial cells,” Blood, vol. 104, no. 7, pp. 2073–2080, 2004.
- A. Nagai, E. Nakagawa, H. B. Choi, K. Hatori, S. Kobayashi, and S. U. Kim, “Erythropoietin and erythropoietin receptors in human CNS neurons, astrocytes, microglia, and oligodendrocytes grown in culture,” Journal of Neuropathology and Experimental Neurology, vol. 60, no. 4, pp. 386–392, 2001.
- K. Chin, X. Yu, B. Beleslin-Cokic et al., “Production and processing of erythropoietin receptor transcripts in brain,” Molecular Brain Research, vol. 81, no. 1-2, pp. 29–42, 2000.
- J. W. Fisher, “Erythropoietin: physiology and pharmacology update,” Experimental Biology and Medicine, vol. 228, no. 1, pp. 1–14, 2003.
- Z. Z. Chong, J.-Q. Kang, and K. Maiese, “Hematopoietic factor erythropoietin fosters neuroprotection through novel signal transduction cascades,” Journal of Cerebral Blood Flow and Metabolism, vol. 22, no. 5, pp. 503–514, 2002.
- M. B. Marrero, R. C. Venema, H. Ma, B. N. Ling, and D. C. Eaton, “Erythropoietin receptor-operated Ca2+ channels: activation by phospholipase C-γ1,” Kidney International, vol. 53, no. 5, pp. 1259–1268, 1998.
- W. Jelkmann, “The enigma of the metabolic fate of circulating erythropoietin (Epo) in view of the pharmacokinetics of the recombinant drugs rhEpo and NESP,” European Journal of Haematology, vol. 69, no. 5-6, pp. 265–274, 2002.
- M. Brines and A. Cerami, “Emerging biological roles for erythropoietin in the nervous system,” Nature Reviews Neuroscience, vol. 6, no. 6, pp. 484–494, 2005.
- M. Brines, G. Grasso, F. Fiordaliso et al., “Erythropoietin mediates tissue protection through an erythropoietin and common β-subunit heteroreceptor,” Proceedings of the National Academy of Sciences of the United States of America, vol. 101, no. 41, pp. 14907–14912, 2004.
- S. Erbayraktar, G. Grasso, A. Sfacteria et al., “Asialoerythropoietin is a nonerythropoietic cytokine with broad neuroprotective activity in vivo,” Proceedings of the National Academy of Sciences of the United States of America, vol. 100, no. 11, pp. 6741–6746, 2003.
- T. Shingo, S. Todd Sorokan, T. Shimazaki, and S. Weiss, “Erythropoietin regulates the in vitro and in vivo production of neuronal progenitors by mammalian forebrain neural stem cells,” Journal of Neuroscience, vol. 21, no. 24, pp. 9733–9743, 2001.
- C. T. Noguchi, P. Asavaritikrai, R. Teng, and Y. Jia, “Role of erythropoietin in the brain,” Critical Reviews in Oncology/Hematology, vol. 64, no. 2, pp. 159–171, 2007.
- S. Masuda, M. Nagao, K. Takahata et al., “Functional erythropoietin receptor of the cells with neural characteristics. Comparison with receptor properties of erythroid cells,” Journal of Biological Chemistry, vol. 268, no. 15, pp. 11208–11216, 1993.
- C. Wiessner, P. R. Allegrini, D. Ekatodramis, U. R. Jewell, T. Stallmach, and M. Gassmann, “Increased cerebral infarct volumes in polyglobulic mice overexpressing erythropoietin,” Journal of Cerebral Blood Flow and Metabolism, vol. 21, no. 7, pp. 857–864, 2001.
- G. Acs, P. Acs, S. M. Beckwith et al., “Erythropoietin and erythropoietin receptor expression in human cancer,” Cancer Research, vol. 61, no. 9, pp. 3561–3565, 2001.
- B. Leyland-Jones and J. A. O'Shaughnessy, “Erythropoietin as a critical component of breast cancer therapy: survival, synergistic, and cognitive applications,” Seminars in Oncology, vol. 30, no. 5, supplement 16, pp. 174–184, 2003.
- R. Yamaji, T. Okada, M. Moriya et al., “Brain capillary endothelial cells express two forms of erythropoietin receptor mRNA,” European Journal of Biochemistry, vol. 239, no. 2, pp. 494–500, 1996.
- A. Mammis, T. K. McIntosh, and A. H. Maniker, “Erythropoietin as a neuroprotective agent in traumatic brain injury. Review,” Surgical Neurology, vol. 71, no. 5, pp. 527–531, 2009.
- M. Digicaylioglu and S. A. Lipton, “Erythropoietin-mediated neuroprotection involves cross-talk between Jak2 and NF-κB signalling cascades,” Nature, vol. 412, no. 6847, pp. 641–647, 2001.
- E. Morishita, S. Masuda, M. Nagao, Y. Yasuda, and R. Sasaki, “Erythropoetin receptor is expressed in rat hippocampal and cerebral cortical neurons, and erythropoietin prevents in vitro glutamate-induced neuronal death,” Neuroscience, vol. 76, no. 1, pp. 105–116, 1996.
- M. Hasselblatt, H. Ehrenreich, and A. L. Sirén, “The brain erythropoietin system and its potential for therapeutic exploitation in brain disease,” Journal of Neurosurgical Anesthesiology, vol. 18, no. 2, pp. 132–138, 2006.
- P. Villa, J. Van Beek, A. K. Larsen et al., “Reduced functional deficits, neuroinflammation, and secondary tissue damage after treatment of stroke by nonerythropoietic erythropoietin derivatives,” Journal of Cerebral Blood Flow and Metabolism, vol. 27, no. 3, pp. 552–563, 2007.
- A. Mahmood, D. Lu, C. Qu et al., “Treatment of traumatic brain injury in rats with erythropoietin and carbamylated erythropoietin,” Journal of Neurosurgery, vol. 107, no. 2, pp. 392–397, 2007.
- Y. Wang, Z. G. Zhang, K. Rhodes et al., “Post-ischemic treatment with erythropoietin or carbamylated erythropoietin reduces infarction and improves neurological outcome in a rat model of focal cerebral ischemia,” British Journal of Pharmacology, vol. 151, no. 8, pp. 1377–1384, 2007.
- G. Grasso, A. Sfacteria, S. Erbayraktar et al., “Amelioration of spinal cord compressive injury by pharmacological preconditioning with erythropoietin and a nonerythropoietic erythropoietin derivative,” Journal of Neurosurgery: Spine, vol. 4, no. 4, pp. 310–318, 2006.
- M. Nangaku, Y. Izuhara, S. Takizawa et al., “A novel class of prolyl hydroxylase inhibitors induces angiogenesis and exerts organ protection against ischemia,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 27, no. 12, pp. 2548–2554, 2007.
- M. A. Puchowicz, J. L. Zechel, J. Valerio et al., “Neuroprotection in diet-induced ketotic rat brain after focal ischemia,” Journal of Cerebral Blood Flow and Metabolism, vol. 28, no. 12, pp. 1907–1916, 2008.
- M. Suzuki, M. Suzuki, Y. Kitamura et al., “β-hydroxybutyrate, a cerebral function improving agent, protects rat brain against ischemic damage caused by permanent and transient focal cerebral ischemia,” Japanese Journal of Pharmacology, vol. 89, no. 1, pp. 36–43, 2002.
- W. Jelkmann, “'O', erythropoietin carbamoylation versus carbamylation,” Nephrology Dialysis Transplantation, vol. 23, no. 9, p. 3033, 2008.
- G. Marfia, L. Madaschi, F. Marra et al., “Adult neural precursors isolated from post mortem brain yield mostly neurons: an erythropoietin-dependent process,” Neurobiology of Disease, vol. 43, no. 1, pp. 86–98, 2011.
- M. Sakanaka, T. C. Wen, S. Matsuda et al., “In vivo evidence that erythropoietin protects neurons from ischemic damage,” Proceedings of the National Academy of Sciences of the United States of America, vol. 95, no. 8, pp. 4635–4640, 1998.
- M. A. Catania, M. C. Marciano, A. Parisi et al., “Erythropoietin prevents cognition impairment induced by transient brain ischemia in gerbils,” European Journal of Pharmacology, vol. 437, no. 3, pp. 147–150, 2002.
- F. Zhang, A. P. Signore, Z. Zhou, S. Wang, G. Cao, and J. Chen, “Erythropoietin protects CA1 neurons against global cerebral ischemia in rat: potential signaling mechanisms,” Journal of Neuroscience Research, vol. 83, no. 7, pp. 1241–1251, 2006.
- M. Bernaudin, H. H. Marti, S. Roussel et al., “A potential role for erythropoietin in focal permanent cerebral ischemia in mice,” Journal of Cerebral Blood Flow and Metabolism, vol. 19, no. 6, pp. 643–651, 1999.
- W. A. Banks, N. L. Jumbe, C. L. Farrell, M. L. Niehoff, and A. C. Heatherington, “Passage of erythropoietic agents across the blood-brain barrier: a comparison of human and murine erythropoietin and the analog darbepoetin alfa,” European Journal of Pharmacology, vol. 505, no. 1–3, pp. 93–101, 2004.
- R. J. Boado, E. K.-W. Hui, J. Z. Lu, and W. M. Pardridge, “Drug targeting of erythropoietin across the primate blood-brain barrier with an IgG molecular trojan horse,” Journal of Pharmacology and Experimental Therapeutics, vol. 333, no. 3, pp. 961–969, 2010.
- H. Ehrenreich, K. Weissenborn, H. Prange et al., “Recombinant human erythropoietin in the treatment of acute ischemic stroke,” Stroke, vol. 40, no. 12, pp. e647–e656, 2009.
- A. Fu, E. K.-W. Hui, J. Z. Lu, R. J. Boado, and W. M. Pardridge, “Neuroprotection in experimental stroke in the rat with an IgG-erythropoietin fusion protein,” Brain Research, vol. 1360, pp. 193–197, 2010.
- W. M. Pardridge, Y. -S. Kang, J. L. Buciak, and J. Yang, “Human insulin receptor monoclonal antibody undergoes high affinity binding to human brain capillaries in vitro and rapid transcytosis through the blood-brain barrier in vivo in the primate,” Pharmaceutical Research, vol. 12, no. 6, pp. 807–816, 1995.
- R. J. Boado and W. M. Pardridge, “Comparison of blood-brain barrier transport of Glial-Derived Neurotrophic Factor (GDNF) and an IgG-GDNF fusion protein in the rhesus monkey,” Drug Metabolism and Disposition, vol. 37, no. 12, pp. 2299–2304, 2009.
- Q.-H. Zhou, R. J. Boado, J. Z. Lu, E. K.-W. Hui, and W. M. Pardridge, “Re-engineering erythropoietin as an IgG fusion protein that penetrates the blood-brain barrier in the mouse,” Molecular Pharmaceutics, vol. 7, no. 6, pp. 2148–2155, 2010.
- Q. -H. Zhou, E. K.-W. Hui, J. Z. Lu, R. J. Boado, and W. M. Pardridge, “Brain penetrating IgG-erythropoietin fusion protein is neuroprotective following intravenous treatment in Parkinson's disease in the mouse,” Brain Research, vol. 1382, pp. 315–320, 2011.
- M. L. Brines, P. Ghezzi, S. Keenan et al., “Erythropoietin crosses the blood-brain barrier to protect against experimental brain injury,” Proceedings of the National Academy of Sciences of the United States of America, vol. 97, no. 19, pp. 10526–10531, 2000.
- A. Gorio, N. Gokmen, S. Erbayraktar et al., “Recombinant human erythropoietin counteracts secondary injury and markedly enhances neurological recovery from experimental spinal cord trauma,” Proceedings of the National Academy of Sciences of the United States of America, vol. 99, no. 14, pp. 9450–9455, 2002.
- A. Gorio, L. Madaschi, B. Di Stefano et al., “Methylprednisolone neutralizes the beneficial effects of erythropoietin in experimental spinal cord injury,” Proceedings of the National Academy of Sciences of the United States of America, vol. 102, no. 45, pp. 16379–16384, 2005.
- Y. Arishima, T. Setoguchi, I. Yamaura, K. Yone, and S. Komiya, “Preventive effect of erythropoietin on spinal cord cell apoptosis following acute traumatic injury in rats,” Spine, vol. 31, no. 21, pp. 2432–2438, 2006.
- B. O. Boran, A. Colak, and M. Kutlay, “Erythropoietin enhances neurological recovery after experimental spinal cord injury,” Restorative Neurology and Neuroscience, vol. 23, no. 5-6, pp. 341–345, 2005.
- F. Fumagalli, L. Madaschi, P. Brenna et al., “Single exposure to erythropoietin modulates Nerve Growth Factor expression in the spinal cord following traumatic injury: comparison with methylprednisolone,” European Journal of Pharmacology, vol. 578, no. 1, pp. 19–27, 2008.
- E. Kaptanoglu, I. Solaroglu, O. Okutan, H. S. Surucu, F. Akbiyik, and E. Beskonakli, “Erythropoietin exerts neuroprotection after acute spinal cord injury in rats: effect on lipid peroxidation and early ultrastructural findings,” Neurosurgical Review, vol. 27, no. 2, pp. 113–120, 2004.
- O. Okutan, I. Solaroglu, E. Beskonakli, and Y. Taskin, “Recombinant human erythropoietin decreases myeloperoxidase and caspase-3 activity and improves early functional results after spinal cord injury in rats,” Journal of Clinical Neuroscience, vol. 14, no. 4, pp. 364–368, 2007.
- L. Vitellaro-Zuccarello, S. Mazzetti, L. Madaschi, P. Bosisio, A. Gorio, and S. De Biasi, “Erythropoietin-mediated preservation of the white matter in rat spinal cord injury,” Neuroscience, vol. 144, no. 3, pp. 865–877, 2007.
- L. Vitellaro-Zuccarello, S. Mazzetti, L. Madaschi et al., “Chronic erythropoietin-mediated effects on the expression of astrocyte markers in a rat model of contusive spinal cord injury,” Neuroscience, vol. 151, no. 2, pp. 452–466, 2008.
- J. R. Faulkner, J. E. Herrmann, M. J. Woo, K. E. Tansey, N. B. Doan, and M. V. Sofroniew, “Reactive astrocytes protect tissue and preserve function after spinal cord injury,” Journal of Neuroscience, vol. 24, no. 9, pp. 2143–2155, 2004.
- L. Wang, G. Z. Zheng, S. R. Gregg et al., “The Sonic hedgehog pathway mediates carbamylated erythropoietin-enhanced proliferation and differentiation of adult neural progenitor cells,” Journal of Biological Chemistry, vol. 282, no. 44, pp. 32462–32470, 2007.
- L. Wang, M. Chopp, S. R. Gregg et al., “Neural progenitor cells treated with EPO induce angiogenesis through the production of VEGF,” Journal of Cerebral Blood Flow and Metabolism, vol. 28, no. 7, pp. 1361–1368, 2008.
- A.-K. Giese, J. Frahm, R. Hübner et al., “Erythropoietin and the effect of oxygen during proliferation and differentiation of human neural progenitor cells,” BMC Cell Biology, vol. 11, article 94, 2010.