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Vol. 3, No. 1-2, 2006
Issue release date: May 2006

Erythropoietin, a Cytoprotective and Regenerative Cytokine, and the Hypoxic Brain

Pacary E. · Petit E. · Bernaudin M.
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Abstract

Hypoxia and ischemia in the brain often result in brain dysfunctions and neuronal death during both the neonatal and adult periods. Though the mechanisms contributing to brain injury secondary to hypoxia-ischemia are more clearly defined, there are still no pharmacological treatments available to reduce cell death in the ischemic brain. This review highlights the beneficial effects of hypoxia-inducible factors, such as the transcriptional factor hypoxia-inducible factor-1 and its target genes, as both cytoprotective and regenerative factors, and focuses in particular on one of the most well-known: erythropoietin. Altogether, the data presented in this review suggest that further insights into the role of hypoxia-inducible factors would help develop promising strategies to improve the outcome of hypoxia/ischemia-related brain pathologies.



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Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
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References

  1. Dirnagl U, Iadecola C, Moskowitz MA: Pathobiology of ischaemic stroke: an integrated view. Trends Neurosci 1999;22:391–397.
  2. Sharp FR, Bernaudin M: HIF1 and oxygen sensing in the brain. Nat Rev Neurosci 2004;5:437–448.
  3. Marti HH: Erythropoietin and the hypoxic brain. J Exp Biol 2004;207:3233–3242.
  4. Bernaudin M, Marti HH, Roussel S, et al: A potential role for erythropoietin in focal permanent cerebral ischemia in mice. J Cereb Blood Flow Metab 1999;19:643–651.
  5. Siren AL, Knerlich F, Poser W, Gleiter CH, Bruck W, Ehrenreich H: Erythropoietin and erythropoietin receptor in human ischemic/ hypoxic brain. Acta Neuropathol (Berl) 2001;101:271–276.
  6. Sakanaka M, Wen TC, Matsuda S, et al: In vivo evidence that erythropoietin protects neurons from ischemic damage. Proc Natl Acad Sci USA 1998;95:4635–4640.
  7. Maiese K, Li F, Chong ZZ: Erythropoietin in the brain: can the promise to protect be fulfilled? Trends Pharmacol Sci 2004;25:577–583.
  8. Ehrenreich H, Hasselblatt M, Dembowski C, et al: Erythropoietin therapy for acute stroke is both safe and beneficial. Mol Med 2002;8:495–505.
  9. Morishita E, Masuda S, Nagao M, Yasuda Y, Sasaki R: Erythropoietin receptor is expressed in rat hippocampal and cerebral cortical neurons, and erythropoietin prevents in vitro glutamate-induced neuronal death. Neuroscience 1997;76:105–116.
  10. Kawakami M, Iwasaki S, Sato K, Takahashi M: Erythropoietin inhibits calcium-induced neurotransmitter release from clonal neuronal cells. Biochem Biophys Res Commun 2000;279:293–297.
  11. Siren AL, Fratelli M, Brines M, et al: Erythropoietin prevents neuronal apoptosis after cerebral ischemia and metabolic stress. Proc Natl Acad Sci USA 2001;98:4044–4049.
  12. Villa P, Bigini P, Mennini T, et al: Erythropoietin selectively attenuates cytokine production and inflammation in cerebral ischemia by targeting neuronal apoptosis. J Exp Med 2003;198:971–975.
  13. Konishi Y, Chui DH, Hirose H, Kunishita T, Tabira T: Trophic effect of erythropoietin and other hematopoietic factors on central cholinergic neurons in vitro and in vivo. Brain Res 1993;609:29–35.
  14. Böcker-Meffert S, Rosenstiel P, Rohl C, et al: Erythropoietin and VEGF promote neural outgrowth from retinal explants in postnatal rats. Invest Ophthalmol Vis Sci 2002;43:2021–2026.
  15. Kretz A, Happold CJ, Marticke JK, Isenmann S: Erythropoietin promotes regeneration of adult CNS neurons via Jak2/Stat3 and PI3K/AKT pathway activation. Mol Cell Neurosci 2005;29:569–579.
  16. Rosenstein JM, Mani N, Khaibullina A, Krum JM: Neurotrophic effects of vascular endothelial growth factor on organotypic cortical explants and primary cortical neurons. J Neurosci 2003;23:11036–11044.
  17. Wang L, Zhang Z, Wang Y, Zhang R, Chopp M: Treatment of stroke with erythropoietin enhances neurogenesis and angiogenesis and improves neurological function in rats. Stroke 2004;35:1732–1737.
  18. Palmer TD, Willhoite AR, Gage FH: Vascular niche for adult hippocampal neurogenesis. J Comp Neurol 2000;425:479–494.
  19. Studer L, Csete M, Lee SH, et al: Enhanced proliferation, survival, and dopaminergic differentiation of CNS precursors in lowered oxygen. J Neurosci 2000;20:7377–7383.
  20. Shingo T, Sorokan ST, Shimazaki T, Weiss S: Erythropoietin regulates the in vitro and in vivo production of neuronal progenitors by mammalian forebrain neural stem cells. J Neurosci 2001;21:9733–9743.
  21. Csete M, Rodriguez L, Wilcox M, Chadalavada S: Erythropoietin receptor is expressed on adult rat dopaminergic neurons and erythropoietin is neurotrophic in cultured dopaminergic neuroblasts. Neurosci Lett 2004;359:124–126.
  22. Jin K, Zhu Y, Sun Y, Mao XO, Xie L, Greenberg DA: Vascular endothelial growth factor (VEGF) stimulates neurogenesis in vitro and in vivo. Proc Natl Acad Sci USA 2002;99:11946–11950.
  23. Kan I, Melamed E, Offen D: Integral therapeutic potential of bone marrow mesenchymal stem cells. Curr Drug Targets 2005;6:31–41.
  24. Bang OY, Lee JS, Lee PH, Lee G: Autologous mesenchymal stem cell transplantation in stroke patients. Ann Neurol 2005;57:874–882.
  25. Hanabusa K, Nagaya N, Iwase T, et al: Adrenomedullin enhances therapeutic potency of mesenchymal stem cells after experimental stroke in rats. Stroke 2005;36:853–858.
  26. Pacary E, Legros H, Valable S, Duchatelle P, Lecocq M, Petit E, Nicole O, Bernaudin M: Synergistic effects of CoCl2 and ROCK inhibition on mesenchymal stem cell differentiation into neuron-like cells. J Cell Sci, in press.
  27. Erbayraktar S, Grasso G, Sfacteria A, et al: Asialoerythropoietin is a nonerythropoietic cytokine with broad neuroprotective activity in vivo. Proc Natl Acad Sci USA 2003;100:6741–6746.
  28. Leist M, Ghezzi P, Grasso G, et al: Derivatives of erythropoietin that are tissue protective but not erythropoietic. Science 2004;305:239–242.
  29. Tang Y, Pacary E, Freret T, et al: Effect of hypoxic preconditioning on brain genomic response before and following ischemia in the adult mouse: identification of potential neuroprotective candidates for stroke. Neurobiol Dis 2006;21:18–28.
  30. Bernaudin M, Tang Y, Reilly M, Petit E, Sharp FR: Brain genomic response following hypoxia and re-oxygenation in the neonatal rat. Identification of genes that might contribute to hypoxia-induced ischemic tolerance. J Biol Chem 2002;277:39728–39738.


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