Neuroprotective properties of epoetin alfa

被引:64
作者
Cerami, A
Brines, M
Ghezzi, P
Cerami, C
Itri, LM
机构
[1] Kenneth S Warren Inst, Ossining, NY 10562 USA
[2] Mario Negri Inst Pharmacol Res, Dept Mol Biochem & Pharmacol, I-20157 Milan, Italy
[3] Genta Inc, Berkeley Hts, NJ USA
关键词
brain injury; encephalitis; epoetin alfa; erythropoietin; ischaemia; neuroprotection;
D O I
10.1093/ndt/17.suppl_1.8
中图分类号
R3 [基础医学]; R4 [临床医学];
学科分类号
1001 ; 1002 ; 100602 ;
摘要
Erythropoietin and its receptor function as primary mediators of the normal physiological response to hypoxia. Erythropoietin is recognized for its central role in erythropoiesis, but studies in which recombinant human erythropoietin (epoetin alfa) is injected directly into ischaemic rodent brain show that erythropoietin also mediates neuroprotection. Abundant expression of the erythropoietin receptor has been observed at brain capillaries, which could provide a route for circulating erythropoietin to enter the brain. In confirmation of this hypothesis. systemic administration of epoetin alfa before or up to 6 h after focal brain ischaemia reduced injury by 50-75%. Epoetin alfa also limited the extent of concussive brain injury, the immune damage in experimental autoimmune encephalomyelitis and excitotoxicity induced by kainate. Thus. systemically administered epoetin alfa in animal models has neuroprotective effects, demonstrating its potential use after brain injury, trauma and multiple sclerosis. It is evident that erythropoietin has biological activities in addition to increasing red cell mass. Given the excellent safety profile of epoetin alfa, clinical trials evaluating systemically administered epoetin alfa as a general neuroprotective treatment are warranted.
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页码:8 / 12
页数:5
相关论文
共 12 条
  • [1] Bernaudin M, 2000, GLIA, V30, P271, DOI 10.1002/(SICI)1098-1136(200005)30:3<271::AID-GLIA6>3.0.CO
  • [2] 2-H
  • [3] Erythropoietin crosses the blood-brain barrier to protect against experimental brain injury
    Brines, ML
    Ghezzi, P
    Keenan, S
    Agnello, D
    de Lanerolle, NC
    Cerami, C
    Itri, LM
    Cerami, A
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2000, 97 (19) : 10526 - 10531
  • [4] Pathobiology of ischaemic stroke: an integrated view
    Dirnagl, U
    Iadecola, C
    Moskowitz, MA
    [J]. TRENDS IN NEUROSCIENCES, 1999, 22 (09) : 391 - 397
  • [5] DIXON C E, 1988, Journal of Neurotrauma, V5, P91, DOI 10.1089/neu.1988.5.91
  • [6] GATA-1 and erythropoietin cooperate to promote erythroid cell survival by regulating bcl-xL expression
    Gregory, T
    Yu, CN
    Ma, A
    Orkin, SH
    Blobel, GA
    Weiss, MJ
    [J]. BLOOD, 1999, 94 (01) : 87 - 96
  • [7] Hillman RS, 1996, RED CELL MANUAL
  • [8] Drug delivery to the brain
    Pardridge, WM
    [J]. JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 1997, 17 (07) : 713 - 731
  • [9] In vivo evidence that erythropoietin protects neurons from ischemic damage
    Sakanaka, M
    Wen, TC
    Matsuda, S
    Masuda, S
    Morishita, E
    Nagao, M
    Sasaki, R
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (08) : 4635 - 4640
  • [10] Erythropoietin can induce the expression of Bcl-xL through Stat5 in erythropoietin-dependent progenitor cell lines
    Silva, M
    Benito, A
    Sanz, C
    Prosper, F
    Ekhterae, D
    Nuñez, G
    Fernandez-Luna, JL
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (32) : 22165 - 22169