Erythropoietin in stroke: Quo vadis

Expert Opinion on Biological Therapy

Volumn 10, Issue 6, 2010, Pages 937-949

  Digicaylioglu, Murat ^a  

^a Mays Cancer Center at UT Health San Antonio   (United States)

Author keywords

Bloodbrain barrier; Drug targeting; Erythropoietin; Intranasal administration; Ischemia; Neuroprotection; RtPA; Stroke; Systemic administration; Therapeutic strategies

Indexed keywords

ALTEPLASE; NANOPARTICLE; PLACEBO; RECOMBINANT ERYTHROPOIETIN; SODIUM CHLORIDE;

BLOOD BRAIN BARRIER; BRAIN ISCHEMIA; DRUG ADMINISTRATION ROUTE; DRUG DELIVERY SYSTEM; DRUG EFFICACY; DRUG MECHANISM; DRUG PENETRATION; NEUROPROTECTION; NONHUMAN; PRACTICE GUIDELINE; REVIEW; STROKE; TREATMENT RESPONSE;

ADMINISTRATION, INTRANASAL; ANIMALS; BRAIN ISCHEMIA; DRUG DELIVERY SYSTEMS; ERYTHROPOIETIN, RECOMBINANT; HUMANS; INJECTIONS, INTRAVENTRICULAR; NANOPARTICLES; NEUROPROTECTIVE AGENTS; STROKE;

ANIMALIA;

EID: 77952168803     PISSN: 14712598     EISSN: None     Source Type: Journal    
DOI: 10.1517/14712598.2010.481435     Document Type: Review

References (107)

1. Lloyd-Jones D, Adams R, Carnethon M, et al.. Heart disease and stroke statistics--2009 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation 2009;119(3):480-486
2. California Acute Stroke Pilot Registry (CASPR) Investigators. Prioritizing interventions to improve rates of thrombolysis for ischemic stroke. Neurology 2005;64(4):654-659
3. Kleindorfer D, Lindsell CJ, Brass LV. National US estimates of recombinant tissue plasminogen activator use: ICD-9 codes substantially underestimate. Stroke 2008;39(3):924-928
4. Arcasoy MO. The non-haematopoietic biological effects of erythropoietin. Br J Haematol 2008;141(1):14-31
5. Noguchi CT, Wang L, Rogers HM, et al.. Survival and proliferative roles of erythropoietin beyond the erythroid lineage. Expert Rev Mol Med 2008;10:e36. Published online 01 December 2008, doi:10.1017/ S1462399408000860
6. Elliott S, Busse L, Bass MB, et al.. Anti-Epo receptor antibodies do not predict Epo receptor expression. Blood 2006;107(5):1892-1895 (Pubitemid 43289368)
7. Kirkeby A, van Beek J, Nielsen J, et al.. Functional and immunochemical characterisation of different antibodies against the erythropoietin receptor. J Neurosci Methods 2007;164(1):50-58
8. Sinclair AM, Coxon A, McCaffery I, et al.. Functional erythropoietin receptor is undetectable in endothelial, cardiac, neuronal, and renal cells. Blood 2010. [Epub ahead of print]
9. Chen ZY, Warin R, Noguchi CT. Erythropoietin and normal brain development: receptor expression determines multi-tissue response. Neurodegener Dis 2006;3(1-2):68-75
10. Kilic E, Kilic U, Soliz J, et al.. Brain-derived erythropoietin protects from focal cerebral ischemia by dual activation of ERK-1/-2 and Akt pathways. FASEB 2005;19(14):2026-2028
11. Tsai PS, Ohab JJ, Kertesz N, et al.. A critical role or erythropoietin receptor in neurogenesis and post-stroke recovery. J Neurosci 2006;26(4):1269-1274
12. Yu X, Shacka JJ, Eells JB, et al.. Erythropoietin receptor signalling is required for normal brain development. Development 2002;129(2):505-516
13. Chen ZY, Asavaritikrai P, Prchal JT, Noguchi CT. Endogenous erythropoietin signaling is required for normal neural progenitor cell proliferation. J Biol Chem 2007;282(35):25875-25883
14. Kadota T, Shingo T, Yasuhara T, et al.. Continuous intraventricular infusion of erythropoietin exerts neuroprotective/ rescue effects upon Parkinson's disease model of rats with enhanced neurogenesis. Brain Res 2009;1254:120-127
15. Carmichael ST. Cellular and molecular mechanisms of neural repair after stroke: making waves. Ann Neurol 2006;59(5):735-742
16. Ohab JJ, Carmichael ST. Poststroke neurogenesis: emerging principles of migration and localization of immature neurons. Neuroscientist 2008;14(4):369-380
17. Morishita E, Masuda S, Nagao M, et al.. Erythropoietin receptor is expressed in rat hippocampal and cerebral cortical neurons, and erythropoietin prevents in vitro glutamate-induced neuronal death. Neuroscience 1997;76(1):105-116
18. Digicaylioglu M, Lipton SA. Erythropoietin-mediated neuroprotection involves cross-talk between Jak2 and NF-kB signalling cascades. Nature 2001;412(6847):641-647
19. 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(8):4635-4640
20. Konishi Y, Chui DH, Hirose H, et al.. Trophic effect of erythropoietin and other hematopoietic factors on central cholinergic neurons in vitro and in vivo. Brain Res 1993;609(1-2):29-35
21. Chong ZZ, Kang JQ, Maiese K. Erythropoietin is a novel vascular protectant through activation of Akt1 and mitochondrial modulation of cysteine proteases. Circulation 2002;106(23):2973-2979
22. Chong ZZ, Kang JQ, Maiese K. Angiogenesis and plasticity: role of erythropoietin in vascular systems. J Hematother Stem Cell Res 2002;11(6):863-871
23. Diaz Z, Assaraf MI, Miller WH Jr, Schipper HM. Astroglial cytoprotection by erythropoietin pre-conditioning: implications for ischemic and degenerative CNS disorders. J Neurochem 2005;93(2):392-402
24. Grasso G, Sfacteria A, Meli F, et al.. Neuroprotection by erythropoietin administration after experimental traumatic brain injury. Brain Res 2007;1182:99-105
25. Gorio A, Gokmen N, Erbayraktar S, et al.. Recombinant human erythropoietin counteracts secondary injury and markedly enhances neurological recovery from experimental spinal cord trauma. Proc Natl Acad Sci USA 2002;99(14):9450-9455
26. Grasso G, Sfacteria A, Erbayraktar S, et al.. Amelioration of spinal cord compressive injury by pharmacological preconditioning with erythropoietin and a nonerythropoietic erythropoietin derivative. J Neurosurg Spine 2006;4(4):310-318
27. Mann C, Lee JH, Liu J, et al.. Delayed treatment of spinal cord injury with erythropoietin or darbepoetin--a lack of neuroprotective efficacy in a contusion model of cord injury. Exp Neurol 2008;211(1):34-40
28. Li Y, Lu ZY, Ogle M, Wei L. Erythropoietin prevents blood brain barrier damage induced by focal cerebral ischemia in mice. Neurochem Res 2007;32(12):2132-2141
29. Chi OZ, Hunter C, Liu X, Weiss HR. Effects of erythropoietin on blood-brain barrier disruption in focal cerebral ischemia. Pharmacology 2008;82(1):38-42 (Pubitemid 351931408)
30. Ehrenreich H, Hasselblatt M, Dembowski C, et al.. Erythropoietin therapy for acute stroke is both safe and beneficial. Mol Med 2002;8(8):495-505
31. Ehrenreich H, Weissenborn K, Prange H, et al.. Recombinant human erythropoietin in the treatment of acute ischemic stroke. Stroke 2009;40(12):e647-56
32. Unger EF, Thompson AM, Blank MJ, Temple R. Erythropoiesis-stimulating agents--time for a reevaluation. N Eng J Med 2010;362(3):189-192
33. Kaur J, Zhao Z, Klein GM, et al.. The neurotoxicity of tissue plasminogen activator? J Cereb Blood Flow Metab 2004;24(9):945-963
34. Ginsberg MD. Current status of neuroprotection for cerebral ischemia: synoptic overview. Stroke 2009;40(Suppl 3):S111-14
35. Fisher M, Bastan B. Treating acute ischemic stroke. Curr Opin Drug Discov Devel 2008;11(5):626-632
36. Fisher M. Recommendations for advancing development of acute stroke therapies: Stroke Therapy Academic Industry Roundtable 3. Stroke 2003;34(6):1539-1546
37. O'Collins VE, Macleod MR, Donnan GA, et al.. 1,026 experimental treatments in acute stroke. Ann Neurol 2006;59(3):467-477
38. Stroke Therapy Academic Industry Roundtable (STAIR). Recommendations for standards regarding preclinical neuroprotective and restorative drug development. Stroke 1999;30(12):2752-2758
39. Stroke Therapy Academic Industry Roundtable II (STAIR-II). Recommendations for clinical trial evaluation of acute stroke therapies. Stroke 2001;32(7):1598-1606
40. Fisher M, Albers GW, Donnan GA, et al.. Enhancing the development and approval of acute stroke therapies: Stroke Therapy Academic Industry roundtable. Stroke 2005;36(8):1808-1813
41. Fisher M, Hanley DF, Howard G, et al.. Recommendations from the STAIR V meeting on acute stroke trials, technology and outcomes. Stroke 2007;38(2):245-248
42. Fisher M, Feuerstein G, Howells DW, et al.. Update of the stroke therapy academic industry roundtable preclinical recommendations. Stroke 2009;40(6):2244-2250
43. Zlokovic BV. The blood--brain barrier in health and chronic neurodegenerative disorders. Neuron 2008;57(2):178-201
44. Butt AM, Jones HC, Abbott NJ. Electrical resistance across the blood--brain barrier in anaesthetized rats: a developmental study. J Physiol 1990;429:47-62
45. Brines ML, Ghezzi P, Keenan S, et al.. Erythropoietin crosses the blood-brain barrier to protect against experimental brain injury. Proc Natl Acad Sci USA 2000;97(19):10526-10531
46. Minnerup J, Heidrich J, Rogalewski A, et al.. The efficacy of erythropoietin and its analogues in animal stroke models: a meta-analysis. Stroke 2009;40(9):3113-3120
47. Pardridge WM. Drug targeting to the brain. Pharm Res 2007;24(9):1733-1744
48. Pardridge WM. Blood--brain barrier delivery. Drug Discov Today 2007;12(1-2):54-61
49. Habgood MD, Bye N, Dziegielewska KM, et al.. Changes in blood-brain barrier permeability to large and small molecules following traumatic brain injury in mice. Eur J Neurosci 2007;25(1):231-238
50. Banks WA, Jumbe NL, Farrell CL, et al.. Passage of erythropoietic agents across the blood--brain barrier: a comparison of human and murine erythropoietin and the analog darbepoetin alfa. Eur J Pharmacol 2004;505(1-3):93-101
51. 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(6):643-651
52. Wakida K, Shimazawa M, Hozumi I, et al.. Neuroprotective effect of erythropoietin, and role of metallothionein-1 and -2, in permanent focal cerebral ischemia. Neuroscience 2007;148(1):105-114
53. Wang Y, Zhang ZG, Rhodes K, et al.. 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 2007;151(8):1377-1384
54. Jeong Lee H, Pardridge WM. Drug targeting to the brain using avidin-biotin technology in the mouse; (blood--brain barrier, monoclonal antibody, transferrin receptor, Alzheimer's disease). J Drug Target 2000;8(6):413-424
55. Spector R, Mock D. Biotin transport through the blood-brain barrier. J Neurochem 1987;48(2):400-404 (Pubitemid 17005146)
56. Shi F, Bailey C, Malick AW, Audus KL. Biotin uptake and transport across bovine brain microvessel endothelial cell monolayers. Pharm Res 1993;10(2):282-288
57. Pillai DR, Dittmar MS, Baldaranov D, et al.. Cerebral ischemia-reperfusion injury in rats-a 3 T MRI study on biphasic blood--brain barrier opening and the dynamics of edema formation. J Cereb Blood Flow Metab 2009;29(11):1846-1855
58. Lo EH, Singhal AB, Torchilin VP, Abbott NJ. Drug delivery to damaged brain. Brain Res Brain Res Rev 2001;38(1-2):140-148
59. Belayev L, Busto R, Zhao W, Ginsberg MD. Quantitative evaluation of blood--brain barrier permeability following middle cerebral artery occlusion in rats. Brain Res 1996;739(1-2):88-96
60. Martinez-Estrada OM, Rodriguez-Millan E, Gonzalez-De Vicente E, et al.. Erythropoietin protects the in vitro blood-brain barrier against VEGF-induced permeability. Eur J Neurosci 2003;18(9):2538-2544
61. Barchet TM, Amiji MM. Challenges and opportunities in CNS delivery of therapeutics for neurodegenerative diseases. Expert Opin Drug Deliv 2009;6(3):211-225
62. Wen TC, Sadamoto Y, Tanaka J, et al.. Erythropoietin protects neurons against chemical hypoxia and cerebral ischemic injury by up-regulating Bcl-xL expression. J Neurosci Res 2002;67(6):795-803
63. Zhang F, Signore AP, Zhou Z, et al.. Erythropoietin protects CA1 neurons against global cerebral ischemia in rat: potential signaling mechanisms. J Neurosci Res 2006;83(7):1241-1251
64. Wu H, Hu K, Jiang X. From nose to brain: understanding transport capacity and transport rate of drugs. Expert Opin Drug Deliv 2008;5(10):1159-1168
65. Hanson LR, Frey WH 2nd. Intranasal delivery bypasses the blood-brain barrier to target therapeutic agents to the central nervous system and treat neurodegenerative disease. BMC Neurosci 2008;9(Suppl 3):S5. Published online 10 December 2008, doi:10.1186/1471-2202-9-S3-S5
66. Freychet L, Rizkalla SW, Desplanque N, et al.. Effect of intranasal glucagon on blood glucose levels in healthy subjects and hypoglycaemic patients with insulin-dependent diabetes. Lancet 1988;1(8599):1364-1366
67. Liu XF, Fawcett JR, Thorne RG, et al.. Intranasal administration of insulin-like growth factor-I bypasses the blood--brain barrier and protects against focal cerebral ischemic damage. J Neurol Sci 2001;187(1-2):91-97
68. Liu XF, Fawcett JR, Thorne RG, Frey WH 2nd. Non-invasive intranasal insulin-like growth factor-I reduces infarct volume and improves neurologic function in rats following middle cerebral artery occlusion. Neurosci Lett 2001;308(2):91-94
69. Ross TM, Martinez PM, Renner JC, et al.. Intranasal administration of interferon beta bypasses the blood-brain barrier to target the central nervous system and cervical lymph nodes: a non-invasive treatment strategy for multiple sclerosis. J Neuroimmunol 2004;151(1-2):66-77
70. Thorne RG, Pronk GJ, Padmanabhan V, Frey WH 2nd. Delivery of insulin-like growth factor-I to the rat brain and spinal cord along olfactory and trigeminal pathways following intranasal administration. Neuroscience 2004;127(2):481-496
71. Yu YP, Xu QQ, Zhang Q, et al.. Intranasal recombinant human erythropoietin protects rats against focal cerebral ischemia. Neurosci Lett 2005;387(1):5-10
72. Reger MA, Watson GS, Frey WH 2nd, et al.. Effects of intranasal insulin on cognition in memory-impaired older adults: modulation by APOE genotype. Neurobiol Aging 2006;27(3):451-458
73. Thorne RG, Hanson LR, Ross TM, et al.. Delivery of interferon-beta to the monkey nervous system following intranasal administration. Neuroscience 2008;152(3):785-797
74. Francis GJ, Martinez JA, Liu WQ, et al.. Intranasal insulin prevents cognitive decline, cerebral atrophy and white matter changes in murine type I diabetic encephalopathy. Brain 2008;131(Pt 12):3311-3334
75. Ma M, Ma Y, Yi X, et al.. Intranasal delivery of transforming growth factorbeta1 in mice after stroke reduces infarct volume and increases neurogenesis in the subventricular zone. BMC Neurosci 2008;9:117. Published online 10 December 2008, doi:10.1186/ 1471-2202-9-117
76. Martinez JA, Francis GJ, Liu WQ, et al.. Intranasal delivery of insulin and a nitric oxide synthase inhibitor in an experimental model of amyotrophic lateral sclerosis. Neuroscience 2008;157(4):908-925
77. Reger MA, Watson GS, Green PS, et al.. Intranasal insulin administration dose-dependently modulates verbal memory and plasma amyloid-beta in memory-impaired older adults. J Alzheimers Dis 2008;13(3):323-331
78. Ross TM, Zuckermann RN, Reinhard C, Frey WH 2nd. Intranasal administration delivers peptoids to the rat central nervous system. Neurosci Lett 2008;439(1):30-33
79. Novakovic ZM, Leinung MC, Lee DW, Grasso P. Intranasal administration of mouse [D-Leu-4]OB3, a synthetic peptide amide with leptin-like activity, enhances total uptake and bioavailability in Swiss Webster mice when compared to intraperitoneal, subcutaneous, and intramuscular delivery systems. Regul Pept 2009;154(1-3):107-111
80. Garcia-Rodriguez JC, Sosa-Teste I. The nasal route as a potential pathway for delivery of erythropoietin in the treatment of acute ischemic stroke in humans. ScientificWorld Journal 2009;9:970-981
81. Hanson L, Roeytenberg A, Martinez PM, et al.. Intranasal deferoxamine provides increased brain exposure and significant protection in rat ischemic stroke. J Pharmacol Exp Ther 2009;330(3):679-686
82. Dhuria SV, Hanson LR, Frey WH 2nd. Intranasal drug targeting of hypocretin-1 (orexin-A) to the central nervous system. J Pharm Sci 2009;98(7):2501-2515
83. Fletcher L, Kohli S, Sprague SM, et al.. Intranasal delivery of erythropoietin plus insulin-like growth factor-I for acute neuroprotection in stroke. J Neurosurg 2009;111(1):164-170
84. Alcala-Barraza SR, Lee MS, Hanson LR, et al.. Intranasal delivery of neurotrophic factors BDNF, CNTF, EPO, and NT-4 to the CNS. J Drug Target 2010;18(3):179-190
85. Yu H, Kim K. Direct nose-to-brain transfer of a growth hormone releasing neuropeptide, hexarelin after intranasal administration to rabbits. Int J Pharm 2009;378(1-2):73-79
86. Hanson LR, Frey WH 2nd. Strategies for intranasal delivery of therapeutics for the prevention and treatment of neuroAIDS. J Neuroimmune Pharmacol 2007;2(1):81-86
87. Pietrowsky R, Struben C, Molle M, et al.. Brain potential changes after intranasal vs intravenous administration of vasopressin: evidence for a direct nose--brain pathway for peptide effects in humans. Biol Psychiatry 1996;39(5):332-340
88. Pietrowsky R, Thiemann A, Kern W, et al.. A nose-brain pathway for psychotropic peptides: evidence from a brain evoked potential study with cholecystokinin. Psychoneuroendocrinology 1996;21(6):559-572
89. Dhuria SV, Hanson LR, Frey WH 2nd. Intranasal delivery to the central nervous system: mechanisms and experimental considerations. J Pharm Sci 2010;99(4):1654-1673
90. Ribatti D, Vacca A, Roccaro AM, et al.. Erythropoietin as an angiogenic factor. Eur J Clin Invest 2003;33(10):891-896
91. Muller-Ehmsen J, Schmidt A, Krausgrill B, et al.. Role of erythropoietin for angiogenesis and vasculogenesis: from embryonic development through adulthood. Am J Physiol Heart Circ Physiol 2006;290(1):H331-40
92. Juul SE, Beyer RP, Bammler TK, et al.. Microarray analysis of high-dose recombinant erythropoietin treatment of unilateral brain injury in neonatal mouse hippocampus. Pediatr Res 2009;65(5):485-492
93. Mahmood A, Lu D, Qu C, et al.. Treatment of traumatic brain injury in rats with erythropoietin and carbamylated erythropoietin. J Neurosurg 2007;107(2):392-397 (Pubitemid 47219384)
94. Danielyan L, Schafer R, von Ameln-Mayerhofer A, et al.. Intranasal delivery of cells to the brain. Eur J Cell Biol 2009;88(6):315-324
95. Balin BJ, Broadwell RD, Salcman M, el-Kalliny M. Avenues for entry of peripherally administered protein to the central nervous system in mouse, rat, and squirrel monkey. J Comp Neurol 1986;251(2):260-280
96. Illum L. Is nose-to-brain transport of drugs in man a reality? J Pharm Pharmacol 2004;56(1):3-17
97. Merkus FW, van den Berg MP. Can nasal drug delivery bypass the blood-brain barrier?: questioning the direct transport theory. Drugs R D 2007;8(3):133-144
98. Digicaylioglu M, Garden G, Timberlake S, et al.. Acute neuroprotective synergy of erythropoietin and insulin-like growth factor I. Proc Natl Acad Sci USA 2004;101(26):9855-9860
99. Diem R, Sattler MB, Merkler D, et al.. Combined therapy with methylprednisolone and erythropoietin in a model of multiple sclerosis. Brain 2005;128(Pt 2):375-385
100. Faure S, Oudart N, Javellaud J, et al.. Synergistic protective effects of erythropoietin and olmesartan on ischemic stroke survival and post-stroke memory dysfunctions in the gerbil. J Hypertens 2006;24(11):2255-2261
101. van der Kooij MA, Groenendaal F, Kavelaars A, et al.. Combination of deferoxamine and erythropoietin: therapy for hypoxia--ischemia-induced brain injury in the neonatal rat? Neurosci Lett 2009;451(2):109-113
102. Ruenraroengsak P, Cook JM, Florence AT. Nanosystem drug targeting: facing up to complex realities. J Control Release 2010;141(3):265-276
103. Jerndal M, Forsberg K, Sena ES, et al.. A systematic review and meta-analysis of erythropoietin in experimental stroke. J Cereb Blood Flow Metab 2009. [Epub ahead of print]
104. Li Y, Lu Z, Keogh CL, et al.. Erythropoietin-induced neurovascular protection, angiogenesis, and cerebral blood flow restoration after focal ischemia in mice. J Cereb Blood Flow Metab 2007;27(5):1043-1054
105. Wang L, Zhang Z, Wang Y, et al.. Treatment of stroke with erythropoietin enhances neurogenesis and angiogenesis and improves neurological function in rats. Stroke 2004;35(7):1732-1737
106. Villa P, Bigini P, Mennini T, et al.. Erythropoietin selectively attenuates cytokine production and inflammation in cerebral ischemia by targeting neuronal apoptosis. Exp Med 2003;198(6):971-975
107. Sadamoto Y, Igase K, Sakanaka M, et al.. Erythropoietin prevents place navigation disability and cortical infarction in rats with permanent occlusion of the middle cerebral artery. Biochem Biophys Res Commun 1998;253(1):26-32