The biology of erythropoietin in the central nervous system and its neurotrophic and neuroprotective potential.
This review summarizes published as well as preliminary data on the biology of erythropoietin (Epo) in the developing and mature human central nervous system (CNS). Both Epo receptor (Epo-R) and Epo gene expression underlie developmental changes and a brain-specific regulation. These features suggest a different role of Epo in normal brain development than in neuroprotection and neuronal tissue repair after brain injury. Epo concentrations in the cerebrospinal fluid may have primary paracrine effects. While the transport of Epo across the intact blood brain barrier (BBB) is generally limited in humans, systemically produced or administrated Epo may cross during BBB dysfunction. Summarized data of the in vivo and in vitro effects of Epo in the CNS show significant neuroprotective and neurotrophic effects of this molecule. These effects are mediated by several mechanisms, including the activation of a variety of genes and their consecutive protein production. Therapeutic strategies involving activation of the CNS Epo-R are discussed, including the potential use of Epo mimetic peptides.
Dame
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Division of Neonatology, Department of Pediatrics, University of Florida, Gainesville 32610-0296, USA.
Juul
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Christensen
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D000818:Animals; D001812:Blood-Brain Barrier; D001921:Brain / Q000196:embryology / Q000254:growth & development*; D001927:Brain Diseases / Q000517:prevention & control*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004921:Erythropoietin / Q000134:cerebrospinal fluid / Q000235:genetics / Q000494:pharmacology / Q000502:physiology* / Q000627:therapeutic use; D005786:Gene Expression Regulation; D006801:Humans; D009474:Neurons / Q000187:drug effects; D012333:RNA, Messenger / Q000032:analysis; D011994:Recombinant Proteins; D013116:Spinal Cord / Q000196:embryology / Q000254:growth & development*
D012333:RNA, Messenger; D011994:Recombinant Proteins; D004921:Erythropoietin