Erythropoietin: Still on the neuroprotection road

Therapeutic Advances in Neurological Disorders

Volumn 5, Issue 3, 2012, Pages 161-173

  Subiras, Nelvys ^a   Del Barco, Diana Garcia ^a   Coro Antich, Rosa M ^b  

^a CENTER FOR GENETIC ENGINEERING AND BIOTECHNOLOGY   (Cuba)

^b CENTRO NACIONAL DE INFORMACIÓN DE CIENCIAS MÉDICAS   (Cuba)

Author keywords

acute stroke; cerebral ischemia; erythropoietin; neuroprotection

Indexed keywords

CARBAMYLATED ERYTHROPOIETIN; CHORIONIC GONADOTROPIN BETA SUBUNIT; EPOPEPTIDE AB; ERYTHROPOIETIN; ERYTHROPOIETIN RECEPTOR; GELATINASE B; HELIX B PEPTIDE; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INTERLEUKIN 1 RECEPTOR ASSOCIATED KINASE 1; JANUS KINASE 2; MITOGEN ACTIVATED PROTEIN KINASE 1; MITOGEN ACTIVATED PROTEIN KINASE 3; NEUROERYTHROPOIETIN; NICOTINAMIDE ADENINE DINUCLEOTIDE ADENOSINE DIPHOSPHATE RIBOSYLTRANSFERASE 1; NOVEL ERYTHROPOIESIS STIMULATING PROTEIN; PEGINESATIDE; PEPTIDOMIMETIC AGENT; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEIN BCL 2; PROTEIN KINASE B; RECOMBINANT ERYTHROPOIETIN; STAT PROTEIN; UNCLASSIFIED DRUG; VASCULOTROPIN; X LINKED INHIBITOR OF APOPTOSIS;

ALZHEIMER DISEASE; ANEMIA; ANGIOGENESIS; APOPTOSIS; ASTROCYTE; BLOOD BRAIN BARRIER; BRAIN EDEMA; BRAIN HEMORRHAGE; BRAIN ISCHEMIA; BRAIN NERVE CELL; CELL PROLIFERATION; COGNITIVE DEFECT; DRUG EFFICACY; DRUG HALF LIFE; DRUG SAFETY; ENCEPHALOMALACIA; ENDOTHELIUM CELL; ENZYME PHOSPHORYLATION; EXCITOTOXICITY; GENE SILENCING; GLIA CELL; HEMATOCRIT; HEMATOPOIESIS; HIPPOCAMPAL CA1 REGION; HUMAN; HYPOXIC ISCHEMIC ENCEPHALOPATHY; INTRACELLULAR SIGNALING; IRON DEFICIENCY; ISCHEMIC PRECONDITIONING; META ANALYSIS (TOPIC); MICROGLIA; NERVE CELL DIFFERENTIATION; NERVOUS SYSTEM DEVELOPMENT; NEUROPROTECTION; NONHUMAN; OLIGODENDROGLIA; OXIDATIVE STRESS; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN PROTEIN INTERACTION; REVIEW; SCHIZOPHRENIA; STROKE; TRAUMATIC BRAIN INJURY; UNSPECIFIED SIDE EFFECT; UPREGULATION; WHITE MATTER;

EID: 84860796183     PISSN: 17562856     EISSN: 17562864     Source Type: Journal    
DOI: 10.1177/1756285611434926     Document Type: Review

References (93)

1. Agnello D. Bigini P. Villa P. Mennini T. Cerami A. Brines M.L. et al. (2002) Erythropoietin exerts an anti-inflammatory effect on the CNS in a model of experimental autoimmune encephalomyelitis. Brain Res 952: 128–134.
2. Bernaudin M. Bellail A. Marti H.H. Yvon A. Vivien D. Duchatelle I. et al. (2000) Neurons and astrocytes express EPO mRNA: oxygen-sensing mechanisms that involve the redox-state of the brain. Glia 30: 271–278.
3. Bernaudin M. Marti H.H. Roussel S. Divoux D. Nouvelot A. Mackenzie E.T. et al. (1999) A potential role for erythropoietin in focal permanent cerebral ischemia in mice. J Cereb Blood Flow Metab 19: 643–651.
4. Bernaudin M. Nedelec A.S. Divoux D. Mackenzie E.T. Petit E. Schumann-Bard P. (2002) Normobaric hypoxia induces tolerance to focal permanent cerebral ischemia in association with an increased expression of hypoxia-inducible factor-1 and its target genes, erythropoietin and VEGF, in the adult mouse brain. J Cereb Blood Flow Metab 22: 393–403.
5. Brines M. Cerami A. (2005) Emerging biological roles for erythropoietin in the nervous system. Nat Rev Neurosci 6: 484–494.
6. Brines M. Ghezzi P. Keenan S. Agnello D. de Lanerolle N.C. Cerami C. et al. (2000) Erythropoietin crosses the blood–brain barrier to protect against experimental brain injury. Proc Natl Acad Sci U S A 97: 10526–10531.
7. Brines M. Grasso G. Fiordaliso F. Sfacteria A. Ghezzi P. Fratelli M. et al. (2004) Erythropoietin mediates tissue protection through an erythropoietin and common beta-subunit heteroreceptor. Proc Natl Acad Sci U S A 101: 14907–14912.
8. Brines M. Patel N.S. Villa P. Brines C. Mennini T. De P.M. et al. (2008) Nonerythropoietic, tissue-protective peptides derived from the tertiary structure of erythropoietin. Proc Natl Acad Sci U S A 105: 10925–10930.
9. Buemi M. Cavallaro E. Floccari F. Sturiale A. Aloisi C. Trimarchi M. et al. (2003) The pleiotropic effects of erythropoietin in the central nervous system. J Neuropathol Exp Neurol 62: 228–236.
10. Calapai G. Marciano M.C. Corica F. Allegra A. Parisi A. Frisina N. et al. (2000) Erythropoietin protects against brain ischemic injury by inhibition of nitric oxide formation. Eur J Pharmacol 401: 349–356.
11. Campana W.M. Li X. Shubayev V.I. Angert M. Cai K. Myers R.R. (2006) Erythropoietin reduces Schwann cell TNF-alpha, Wallerian degeneration and pain-related behaviors after peripheral nerve injury. Eur J Neurosci 23: 617–626.
12. Chen G. Shi J.X. Hang C.H. Xie W. Liu J. Liu X. (2007) Inhibitory effect on cerebral inflammatory agents that accompany traumatic brain injury in a rat model: a potential neuroprotective mechanism of recombinant human erythropoietin (rhEPO). Neurosci Lett 425: 177–182.
13. Cho H.J. Kim Y.J. (2009) Efficacy and safety of oral citicoline in acute ischemic stroke: drug surveillance study in 4,191 cases. Methods Find Exp Clin Pharmacol 31: 171–176.
14. Chong Z.Z. Kang J.Q. Maiese K. (2002) Erythropoietin is a novel vascular protectant through activation of Akt 1 and mitochondrial modulation of cysteine proteases. Circulation 106: 2973–2979.
15. Conant R. Schauss A.G. (2004) Therapeutic applications of citicoline for stroke and cognitive dysfunction in the elderly: a review of the literature. Altern Med Rev 9: 17–31.
16. Cramer S.C. Fitzpatrick C. Warren M. Hill M.D. Brown D. Whitaker L. et al. (2010) The beta-hCG+erythropoietin in acute stroke (BETAS) study: a 3-center, single-dose, open-label, noncontrolled, phase IIa safety trial. Stroke 41: 927–931.
17. Diaz Z. Assaraf M.I. Miller W.H. Jr Schipper H.M. (2005) Astroglial cytoprotection by erythropoietin pre-conditioning: implications for ischemic and degenerative CNS disorders. J Neurochem 93: 392–402.
18. Digicaylioglu M. (2010) Erythropoietin in stroke: quo vadis. Expert Opin Biol Ther 10: 937–949.
19. Digicaylioglu M. Lipton S.A. (2001) Erythropoietin-mediated neuroprotection involves cross-talk between JAK2 and NF-kappaB signalling cascades. Nature 412: 641–647.
20. Ehrenreich H. Degner D. Meller J. Brines M. Behe M. Hasselblatt M. et al. (2004) Erythropoietin: a candidate compound for neuroprotection in schizophrenia. Mol Psychiatry 9: 42–54.
21. Ehrenreich H. Fischer B. Norra C. Schellenberger F. Stender N. Stiefel M. et al. (2007) Exploring recombinant human erythropoietin in chronic progressive multiple sclerosis. Brain 130: 2577–2588.
22. Ehrenreich H. Hasselblatt M. Dembowski C. Cepek L. Lewczuk P. Stiefel M. et al. (2002) Erythropoietin therapy for acute stroke is both safe and beneficial. Mol Med 8: 495–505.
23. Ehrenreich H. Weissenborn K. Prange H. Schneider D. Weimar C. Wartenberg K. et al. (2009) Recombinant human erythropoietin in the treatment of acute ischemic stroke. Stroke 40: e647-e656.
24. Eid T. Brines M.L. Cerami A. Spencer D.D. Kim J.H. Schweitzer J.S. et al. (2004) Increased expression of erythropoietin receptor on blood vessels in the human epileptogenic hippocampus with sclerosis. J Neuropathol Exp Neurol 63: 73–83.
25. Elmahdy H. El-Mashad A.R. El-Bahrawy H. El-Gohary T. El-Barbary A. Aly H. (2010) Human recombinant erythropoietin in asphyxia neonatorum: pilot trial. Pediatrics 125: e1135-e1142.
26. Erbayraktar S. Grasso G. Sfacteria A. Xie Q.W. Coleman T. Kreilgaard M. et al. (2003) Asialoerythropoietin is a nonerythropoietic cytokine with broad neuroprotective activity in vivo. Proc Natl Acad Sci U S A 100: 6741–6746.
27. Fauchere J.C. Dame C. von Thein R. Koller B. Arri S. Wolf M. et al. (2008) An approach to using recombinant erythropoietin for neuroprotection in very preterm infants. Pediatrics 122: 375–382.
28. Fisher J.W. (2003) Erythropoietin: physiology and pharmacology update. Exp Biol Med (Maywood ) 228: 1–14.
29. Fisher M. (2011) New approaches to neuroprotective drug development. Stroke 42: S24-S27.
30. Fisher M. Feuerstein G. Howells D.W. Hurn P.D. Kent T.A. Savitz S.I. et al. (2009) Update of the stroke therapy academic industry roundtable preclinical recommendations. Stroke 40: 2244–2250.
31. Genc S. Koroglu T.F. Genc K. (2002) Erythropoietin as a novel neuroprotectant. Restorative Neurol Neurosci 20: 1–15.
32. Genc S. Koroglu T.F. Genc K. (2004) Erythropoietin and the nervous system. Brain Res 1000: 19–31.
33. Gorio A. Gokmen N. Erbayraktar S. Yilmaz O. Madaschi L. Cichetti C. et al. (2002) Recombinant human erythropoietin counteracts secondary injury and markedly enhances neurological recovery from experimental spinal cord trauma. Proc Natl Acad Sci U S A 99: 9450–9455.
34. Graff C.L. Pollack G.M. (2005) Nasal drug administration: potential for targeted central nervous system delivery. J Pharm Sci 94: 1187–1195.
35. Grasso G. Sfacteria A. Erbayraktar S. Passalacqua M. Meli F. Gokmen N. et al. (2006) Amelioration of spinal cord compressive injury by pharmacological preconditioning with erythropoietin and a nonerythropoietic erythropoietin derivative. J Neurosurg Spine 4: 310–318.
36. Green A.R. (2008) Pharmacological approaches to acute ischaemic stroke: reperfusion certainly, neuroprotection possibly. Br J Pharmacol 153(Suppl. 1): S325-S338.
37. Haljan G. Maitland A. Buchan A. Arora R.C. King M. Haigh J. et al. (2009) The erythropoietin neuroprotective effect: assessment in CABG surgery (TENPEAKS): a randomized, double-blind, placebo controlled, proof-of-concept clinical trial. Stroke 40: 2769–2775.
38. He J.S. Huang Z.L. Yang H. Weng K.Z. Zhu S.B. (2008) [Early use of recombinant human erythropoietin promotes neurobehavioral development in preterm infants]. Zhongguo Dang Dai Er Ke Za Zhi 10: 586–588.
39. Illum L. (2003) Nasal drug delivery–possibilities, problems and solutions. J Control Release 87: 187–198.
40. Jia L. Chopp M. Zhang L. Lu M. Zhang Z. (2010) Erythropoietin in combination of tissue plasminogen activator exacerbates brain hemorrhage when treatment is initiated 6 hours after stroke. Stroke 41: 2071–2076.
41. Juul S. (2002) Erythropoietin in the central nervous system, and its use to prevent hypoxic-ischemic brain damage. Acta Paediatr Suppl 91: 36–42.
42. Kato S. Aoyama M. Kakita H. Hida H. Kato I. Ito T. et al. (2011) Endogenous erythropoietin from astrocyte protects the oligodendrocyte precursor cell against hypoxic and reoxygenation injury. J Neurosci Res 89: 1566–1574.
43. Keswani S.C. Leitz G.J. Hoke A. (2004) Erythropoietin is neuroprotective in models of HIV sensory neuropathy. Neurosci Lett 371: 102–105.
44. Kilic E. Kilic U. Soliz J. Bassetti C.L. Gassmann M. Hermann D.M. (2005) Brain-derived erythropoietin protects from focal cerebral ischemia by dual activation of ERK-1/-2 and Akt pathways. FASEB J 19: 2026–2028.
45. Koshimura K. Murakami Y. Sohmiya M. Tanaka J. Kato Y. (1999) Effects of erythropoietin on neuronal activity. J Neurochem 72: 2565–2572.
46. Koury M.J. Bondurant M.C. (1990) Erythropoietin retards DNA breakdown and prevents programmed death in erythroid progenitor cells. Science 248:378–381.
47. Kumral A. Gonenc S. Acikgoz O. Sonmez A. Genc K. Yilmaz O. et al. (2005) Erythropoietin increases glutathione peroxidase enzyme activity and decreases lipid peroxidation levels in hypoxic-ischemic brain injury in neonatal rats. Biol Neonate 87: 15–18.
48. Leist M. Ghezzi P. Grasso G. Bianchi R. Villa P. Fratelli M. et al. (2004) Derivatives of erythropoietin that are tissue protective but not erythropoietic. Science 305: 239–242.
49. Lewczuk P. Hasselblatt M. Kamrowski-Kruck H. Heyer A. Unzicker C. Siren A.L. et al. (2000) Survival of hippocampal neurons in culture upon hypoxia: effect of erythropoietin. Neuroreport 11: 3485–3488.
50. Li F. Chong Z.Z. Maiese K. (2006) Microglial integrity is maintained by erythropoietin through integration of Akt and its substrates of glycogen synthase kinase-3beta, beta-catenin, and nuclear factor-kappa B. Curr Neurovasc Res 3: 187–201.
51. Liu W. Shen Y. Plane J.M. Pleasure D.E. Deng W. (2011) Neuroprotective potential of erythropoietin and its derivative carbamylated erythropoietin in periventricular leukomalacia. Exp Neurol 230: 227–239.
52. Mahmood A. Lu D. Qu C. Goussev A. Zhang Z.G. Lu C. et al. (2007) Treatment of traumatic brain injury in rats with erythropoietin and carbamylated erythropoietin. J Neurosurg 107: 392–397.
53. Marti H.H. (2004) Erythropoietin and the hypoxic brain. J Exp Biol 207: 3233–3242.
54. Marti H.H. Wenger R.H. Rivas L.A. Straumann U. Digicaylioglu M. Henn V. et al. (1996) Erythropoietin gene expression in human, monkey and murine brain. Eur J Neurosci 8: 666–676.
55. Millan M. Sobrino T. Arenillas J.F. Rodriguez-Yanez M. Garcia M. Nombela F. et al. (2008) Biological signatures of brain damage associated with high serum ferritin levels in patients with acute ischemic stroke and thrombolytic treatment. Dis Markers 25: 181–188.
56. Minnerup J. Heidrich J. Rogalewski A. Schabitz W.R. Wellmann J. (2009) The efficacy of erythropoietin and its analogues in animal stroke models: a meta-analysis. Stroke 40: 3113–3120.
57. Morishita E. Masuda S. Nagao M. Yasuda Y. Sasaki R. (1997) Erythropoietin receptor is expressed in rat hippocampal and cerebral cortical neurons, and erythropoietin prevents in vitro glutamate-induced neuronal death. Neuroscience 76: 105–116.
58. O'Collins V.E. Macleod M.R. Donnan G.A. Horky L.L. van der Worp B.H. Howells D.W. (2006) 1,026 experimental treatments in acute stroke. Ann Neurol 59: 467–477.
59. Pinzon A. Marcillo A. Pabon D. Bramlett H.M. Bunge M.B. Dietrich W.D. (2008) A re-assessment of erythropoietin as a neuroprotective agent following rat spinal cord compression or contusion injury. Exp Neurol 213: 129–136.
60. Prass K. Scharff A. Ruscher K. Lowl D. Muselmann C. Victorov I. et al. (2003) Hypoxia-induced stroke tolerance in the mouse is mediated by erythropoietin. Stroke 34: 1981–1986.
61. Renzi M.J. Farrell F.X. Bittner A. Galindo J.E. Morton M. Trinh H. et al. (2002) Erythropoietin induces changes in gene expression in PC-12 cells. Brain Res Mol Brain Res 104: 86–95.
62. Ruscher K. Freyer D. Karsch M. Isaev N. Megow D. Sawitzki B. et al. (2002) Erythropoietin is a paracrine mediator of ischemic tolerance in the brain: evidence from an in vitro model. J Neurosci 22: 10291–10301.
63. Sadamoto Y. Igase K. Sakanaka M. Sato K. Otsuka H. Sakaki S. et al. (1998) Erythropoietin prevents place navigation disability and cortical infarction in rats with permanent occlusion of the middle cerebral artery. Biochem Biophys Res Commun 253: 26–32.
64. Sakanaka M. Wen T.-C. Matsuda S. Seiji Masuda S. Morishita E. Nagao M. et al. (1998) In vivo evidence that erythropoietin protects neurons from ischemic damage. Proc Natl Acad Sci U S A 95: 4635–4640.
65. Savino C. Pedotti R. Baggi F. Ubiali F. Gallo B. Nava S. et al. (2006) Delayed administration of erythropoietin and its non-erythropoietic derivatives ameliorates chronic murine autoimmune encephalomyelitis. J Neuroimmunol 172: 27–37.
66. Schmidt R.E. Green K.G. Feng D. Dorsey D.A. Parvin C.A. Lee J.M. et al. (2008) Erythropoietin and its carbamylated derivative prevent the development of experimental diabetic autonomic neuropathy in STZ-induced diabetic NOD-SCID mice. Exp Neurol 209: 161–170.
67. Shingo T. Sorokan S.T. Shimazaki T. Weiss S. (2001) Erythropoietin regulates the in vitro and in vivo production of neuronal progenitors by mammalian forebrain neural stem cells. J Neurosci 21: 9733–9743.
68. Shuaib A. Hussain M.S. (2008) The past and future of neuroprotection in cerebral ischaemic stroke. Eur Neurol 59: 4–14.
69. Sinor A.D. Greenberg D.A. (2000) Erythropoietin protects cultured cortical neurons, but not astroglia, from hypoxia and AMPA toxicity. Neurosci Lett 290: 213–215.
70. Siren A.L. Ehrenreich H. (2001) Erythropoietin–a novel concept for neuroprotection. Eur Arch Psychiatry Clin Neurosci 251: 179–184.
71. Siren A.L. Fasshauer T. Bartels C. Ehrenreich H. (2009) Therapeutic potential of erythropoietin and its structural or functional variants in the nervous system. Neurotherapeutics 6: 108–127.
72. Siren A.L. Fratelli M. Brines M. Goemans C. Casagrande S. Lewczuk P. et al. (2001) Erythropoietin prevents neuronal apoptosis after cerebral ischemia and metabolic stress. Proc Natl Acad Sci U S A 98: 4044–4049.
73. Sirén A.-L. Knerlich F. Poser W. Gleiter C. Brück W. Ehrenreich H. (2001) Erythropoietin and erythropoietin receptor in human ischemic / hypoxic brain. Acta Neuropathol (Berl) 101: 271–276.
74. Sola A. Rogido M. Lee B.H. Genetta T. Wen T.C. (2005) Erythropoietin after focal cerebral ischemia activates the Janus kinase-signal transducer and activator of transcription signaling pathway and improves brain injury in postnatal day 7 rats. Pediatr Res 57: 481–487.
75. Sosa I. Mengana Y. García Salman J.D. Subiros N. Cruz J. Muñoz A. et al. (2008) La eritropoyetina humana recombinante como terapia para la neuroprotección en la isquemia cerebral. Biotecnología Aplicada 25: 223–229.
76. Springborg J.B. Sonne B. Frederiksen H.J. Foldager N. Poulsgaard L. Klausen T. et al. (2003) Erythropoietin in the cerebrospinal fluid of patients with aneurysmal subarachnoid haemorrhage originates from the brain. Brain Res 984: 143–148.
77. Subiros Martínez N. Coro Antich R. García Salman J.D. Sosa I. Mengana Y. García Rodríguez J.C. et al. (2007) Efectos neuroprotectores de una formulación nasal de EPOhr-bas sobre la isquemia cerebral. II. Modelo de Isquemia Bilateral Transitoria. In IX Congreso Virtual Hispanoamericano de Anatomía Patológica 2007. Available at: http://www.conganat.org/9congreso/index.asp.
78. Sugawa M. Sakurai Y. Ishikawa-Ieda Y. Suzuki H. Asou H. (2002) Effects of erythropoietin on glial cell development; oligodendrocyte maturation and astrocyte proliferation. Neurosci Res 44: 391–403.
79. Talving P. Lustenberger T. Kobayashi L. Inaba K. Barmparas G. Schnuriger B. et al. (2010) Erythropoiesis stimulating agent administration improves survival after severe traumatic brain injury: a matched case control study. Ann Surg 251: 1–4.
80. Tseng M.Y. Hutchinson P.J. Richards H.K. Czosnyka M. Pickard J.D. Erber W.N. et al. (2009) Acute systemic erythropoietin therapy to reduce delayed ischemic deficits following aneurysmal subarachnoid hemorrhage: a Phase II randomized, double-blind, placebo-controlled trial. Clinical article. J Neurosurg 111: 171–180.
81. van der Kooij M.A. Groenendaal F. Kavelaars A. Heijnen C.J. van B.F. (2008) Neuroprotective properties and mechanisms of erythropoietin in in vitro and in vivo experimental models for hypoxia/ischemia. Brain Res Rev 59: 22–33.
82. Villa P. Bigini P. Mennini T. Agnello D. Laragione T. Cagnotto A. et al. (2003) Erythropoietin selectively attenuates cytokine production and inflammation in cerebral ischemia by targeting neuronal apoptosis. J Exp Med 198: 971–975.
83. Wang L. Zhang Z. Wang Y. Zhang R. Chopp M. (2004 a) Treatment of stroke with erythropoietin enhances neurogenesis and angiogenesis and improves neurological function in rats. Stroke 35: 1732–1737.
84. Wang X. Zhu C. Wang X. Gerwien J.G. Schrattenholz A. Sandberg M. et al. (2004 b) The nonerythropoietic asialoerythropoietin protects against neonatal hypoxia-ischemia as potently as erythropoietin. J Neurochem 91: 900–910.
85. Wang Y. Zhang Z.G. Rhodes K. Renzi M. Zhang R.L. Kapke A. et al. (2007) Post-ischemic treatment with erythropoietin or carbamylated erythropoietin reduces infarction and improves neurological outcome in a rat model of focal cerebral ischemia. Br J Pharmacol 151: 1377–1384.
86. Wen T.C. Sadamoto Y. Tanaka J. Zhu P.X. Nakata K. Ma Y.J. et al. (2002) Erythropoietin protects neurons against chemical hypoxia and cerebral ischemic injury by up-regulating Bcl-xL expression. J Neurosci Res 67:795–803.
87. Wiessner C. Allegrini P.R. Ekatodramis D. Jewell U.R. Stallmach T. Gassmann M. (2001) Increased cerebral infarct volumes in polyglobulic mice overexpressing erythropoietin. J Cereb Blood Flow Metab 21: 857–864.
88. Wu Y. Shang Y. Sun S.G. Liu R.G. Yang W.Q. (2007) Protective effect of erythropoietin against 1-methyl-4-phenylpyridinium-induced neurodegeneration in PC 12 cells. Neurosci Bull 23: 156–164.
89. Yu X. Shacka J.J. Eells J.B. Suarez-Quian C. Przygodzki R.M. Beleslin-Cokic B. et al. (2002) Erythropoietin receptor signalling is required for normal brain development. Development 129: 505–516.
90. Yu Y.-P. Xu Q.-Q. Zhang Q. Zhang W.-P. Zhang L.-H. Wei E.-Q. (2005) Intranasal recombinant human erythropoietin protects rats against focal cerebral ischemia. Neurosci Lett 387: 5–10.
91. Zechariah A. ElAli A. Hermann D.M. (2010) Combination of tissue-plasminogen activator with erythropoietin induces blood-brain barrier permeability, extracellular matrix disaggregation, and DNA fragmentation after focal cerebral ischemia in mice. Stroke 41: 1008–1012.
92. Zhang L. Chopp M. Zhang R.L. Wang L. Zhang J. Wang Y. et al. (2010) Erythropoietin amplifies stroke-induced oligodendrogenesis in the rat. PloS ONE 5: e11016.
93. Zhu C. Kang W. Xu F. Cheng X. Zhang Z. Jia L. et al. (2009) Erythropoietin improved neurologic outcomes in newborns with hypoxic-ischemic encephalopathy. Pediatrics 124: e218–e226.