Beyond erythropoiesis: Novel applications for recombinant human erythropoietin

Beyond erythropoiesis: Novel applications for recombinant human erythropoietin Erythropoietin (EPO) primarily is produced in the kidney and acts as a principal mediator of the physiologic response to hypoxia by increasing red blood cell production. Astrocytes and neurons in the central nervous system (CNS) also are known to produce EPO in response to hypoxia/ischemia. EPO appears to play a neuroprotective role based on preclinical data demonstrating the ability of recombinant human erythropoietin (r-HuEPO) to shield neurons from hypoxic/ischemic stress when administered intracerebraventricularly. In CNS models, systemically administered r-HuEPO has not been intensely investigated because large glycosylated molecules generally were deemed incapable of crossing the blood-brain barrier (BBB). A collaborative research effort identified expression of EPO receptors on human brain capillaries and a specific receptor-mediated transport of r-HuEPO across the BBB after a single intraperitoneal (IP) injection in rodents, with subsequent protection against various types of neuronal damage. For example, administration of r-HuEPO 24 hours before or up to 6 hours after focal ischemic stroke significantly reduced the extent of infarction. r-HuEPO also attenuated concussive brain injury, kainate-induced seizure activity, and autoimmune encephalomyelitis. These preclinical findings suggest that r-HuEPO may have therapeutic potential for stroke, head trauma, and epilepsy; additional studies are needed to confirm and extend these encouraging observations in animal models. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Seminars in Hematology Elsevier

Beyond erythropoiesis: Novel applications for recombinant human erythropoietin

Seminars in Hematology, Volume 38 – Jul 1, 2001

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Publisher
Elsevier
Copyright
Copyright © 2001 Elsevier Ltd
ISSN
0037-1963
eISSN
1532-8686
D.O.I.
10.1016/S0037-1963(01)90128-3
Publisher site
See Article on Publisher Site

Abstract

Erythropoietin (EPO) primarily is produced in the kidney and acts as a principal mediator of the physiologic response to hypoxia by increasing red blood cell production. Astrocytes and neurons in the central nervous system (CNS) also are known to produce EPO in response to hypoxia/ischemia. EPO appears to play a neuroprotective role based on preclinical data demonstrating the ability of recombinant human erythropoietin (r-HuEPO) to shield neurons from hypoxic/ischemic stress when administered intracerebraventricularly. In CNS models, systemically administered r-HuEPO has not been intensely investigated because large glycosylated molecules generally were deemed incapable of crossing the blood-brain barrier (BBB). A collaborative research effort identified expression of EPO receptors on human brain capillaries and a specific receptor-mediated transport of r-HuEPO across the BBB after a single intraperitoneal (IP) injection in rodents, with subsequent protection against various types of neuronal damage. For example, administration of r-HuEPO 24 hours before or up to 6 hours after focal ischemic stroke significantly reduced the extent of infarction. r-HuEPO also attenuated concussive brain injury, kainate-induced seizure activity, and autoimmune encephalomyelitis. These preclinical findings suggest that r-HuEPO may have therapeutic potential for stroke, head trauma, and epilepsy; additional studies are needed to confirm and extend these encouraging observations in animal models.

Journal

Seminars in HematologyElsevier

Published: Jul 1, 2001

References

  • Erythropoietin: Structure, control of production, and function
    Jelkmann, W
  • Neurons and astrocytes express EPO mRNA: Oxygen-sensing mechanisms that involve the redox-state of the brain
    Bernaudin, M; Bellail, A; Marti, HH
  • Erythropoietin gene expression in human, monkey and murine brain
    Marti, HH; Wenger, RH; Rivas, LA
  • Erythropoietin prevents place navigation disability and cortical infarction in rats with permanent occlusion of the middle cerebral artery
    Sadamoto, Y; Igase, K; Sakanaka, M
  • Receptor-mediated transcytosis of transferrin across the blood-brain barrier
    Fishman, JB; Rubin, JB; Handrahan, JV
  • Neurodegeneration in excitotoxicity, global cerebral ischemia, and target deprivation: A perspective on the contributions of apoptosis and necrosis
    Martin, LJ; Al-Abdulla, NA; Brambrink, AM

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