Effects of epoetin alfa on the central nervous system.
Erythropoietin (EPO) is a glycoprotein that has been shown to mediate response to hypoxia, and is most notably recognized for its central role in erythropoiesis. In a series of experiments using rodent models, the ability of systemically administered recombinant human erythropoietin (r-HuEPO, epoetin alfa) to cross the blood-brain barrier and affect the outcome of neuronal injury or cognitive function was evaluated. It was shown that EPO and EPO receptors are expressed at capillaries of the brain-periphery interface, and that systemically administered epoetin alfa crossed the blood-brain barrier. Compared with control animals, epoetin alfa significantly reduced tissue damage in an ischemic stroke model when administered 24 hours before inducing stroke, with significant protection still evident when epoetin alfa was administered 6 hours poststroke. Epoetin alfa reduced injury by blunt trauma when administered 24 hours before trauma, with a significantly smaller volume of tissue necrosis noted when compared with controls. The observation that epoetin alfa may reduce nervous system inflammation was confirmed when an experimental autoimmune encephalomyelitis model in which rats were shown to have significantly delayed onset and reduced severity of experimental autoimmune encephalomyelitis symptoms after treatment with epoetin alfa. Epoetin alfa also was shown to ameliorate the latency and severity of seizures, and significantly increase survival versus controls when exposed to kainate. These findings suggest future potential therapeutic uses for epoetin alfa beyond its current use to increase erythropoiesis.
Cerami
A
A
Kenneth S. Warren Laboratories, Tarrytown, NY, USA.
Brines
M L
ML
Ghezzi
P
P
Cerami
C J
CJ
D000818:Animals; D001812:Blood-Brain Barrier; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002545:Brain Ischemia / Q000517:prevention & control; D002490:Central Nervous System / Q000187:drug effects*; D004679:Encephalomyelitis / Q000517:prevention & control; D000068817:Epoetin Alfa; D004921:Erythropoietin / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D007608:Kainic Acid; D051379:Mice; D023421:Models, Animal; D018696:Neuroprotective Agents / Q000378:metabolism / Q000494:pharmacology*; D017467:Receptors, Erythropoietin / Q000378:metabolism*; D011994:Recombinant Proteins; D012640:Seizures / Q000139:chemically induced / Q000517:prevention & control
D018696:Neuroprotective Agents; D017467:Receptors, Erythropoietin; D011994:Recombinant Proteins; D004921:Erythropoietin; D000068817:Epoetin Alfa; D007608:Kainic Acid