Recombinant human erythropoietin for neuroprotection: what is the evidence?
Erythropoietin (EPO) is an endogenous cytokine with antiapoptotic, antiinflammatory, and neurotrophic properties. Apart from being produced by the kidney, liver, and spleen in response to hypoxia, EPO is highly expressed in the brain during development and after neuropathological insults. The observation that receptors for EPO are present on brain capillaries and glial capillary end-feet has suggested that circulating (plasma) EPO may be transferred into the brain. This review summarizes the increasing number of studies indicating that peripherally administered recombinant human (rHu) EPO crosses the blood-brain barrier. Moreover, several of these studies have shown that peripherally administered rHuEPO can protect against the damage caused by a diversity of neuropathological conditions such as (a) stroke, (b) head and spinal cord trauma, (c) inflammatory and demyelinating conditions, (d) toxin-induced epileptic seizures, and (e) retinal ischemia. While all these studies are based on experiments in animal models, the effectiveness of rHuEPO in ischemic stroke in human patients has recently been suggested in a proof-of-concept trial, which is also discussed.
Eid
Tore
T
Department of Neurosurgery, Yale University School of Medicine, New Haven, Connecticut 06520, USA. tore.eid@yale.edu
Brines
Michael
M
D000818:Animals; D001812:Blood-Brain Barrier; D001930:Brain Injuries / Q000188:drug therapy* / Q000473:pathology / Q000517:prevention & control; D018849:Controlled Clinical Trials as Topic; D003430:Cross-Sectional Studies; D003711:Demyelinating Diseases / Q000188:drug therapy* / Q000517:prevention & control; D004195:Disease Models, Animal; D004921:Erythropoietin / Q000627:therapeutic use*; D019317:Evidence-Based Medicine; D005260:Female; D006801:Humans; D007273:Injections, Intramuscular; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D011817:Rabbits; D051381:Rats; D011994:Recombinant Proteins; D012680:Sensitivity and Specificity; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000473:pathology / Q000517:prevention & control; D020521:Stroke / Q000188:drug therapy* / Q000473:pathology / Q000517:prevention & control; D016896:Treatment Outcome
D018696:Neuroprotective Agents; D011994:Recombinant Proteins; D004921:Erythropoietin