title: Circulating damage marker profiles support a neuroprotective effect of erythropoietin in ischemic stroke patients.
abstract: The German Multicenter EPO Stroke Trial, which investigated safety and efficacy of erythropoietin (EPO) treatment in ischemic stroke, was formally declared a negative study. Exploratory subgroup analysis, however, revealed that patients not receiving thrombolysis most likely benefited from EPO during clinical recovery, a result demonstrated in the findings of the Göttingen EPO Stroke Study. The present work investigated whether the positive signal on clinical outcome in this patient subgroup was mirrored by respective poststroke biomarker profiles. All patients of the German Multicenter EPO Stroke Trial nonqualifying for thrombolysis were included if they (a) were treated per protocol and (b) had at least two of the five follow-up blood samples for circulating damage markers drawn (n = 163). The glial markers S100B and glial fibrillary acid protein (GFAP) and the neuronal marker ubiquitin C-terminal hydrolase (UCH-L1) were measured by enzyme-linked immunosorbent assay in serum on d 1, 2, 3, 4 and 7 poststroke. All biomarkers increased poststroke. Overall, EPO-treated patients had significantly lower concentrations (area under the curve) over 7 d of observation, as reflected by the composite score of all three markers (Cronbach α = 0.811) and by UCH-L1. S100B and GFAP showed a similar tendency. To conclude, serum biomarker profiles, as an outcome measure of brain damage, corroborate an advantageous effect of EPO in ischemic stroke. In particular, reduction in the neuronal damage marker UCH-L1 may reflect neuroprotection by EPO.
authors.affiliation: Clinical Neuroscience, Max Planck Institute of Experimental Medicine, Göttingen, Germany. ehrenreich@em.mpg.de
authors.forename: Hannelore
authors.initials: H
authors.lastname: Ehrenreich
authors.forename: Anne
authors.initials: A
authors.lastname: Kästner
authors.forename: Karin
authors.initials: K
authors.lastname: Weissenborn
authors.forename: Jackson
authors.initials: J
authors.lastname: Streeter
authors.forename: Swetlana
authors.initials: S
authors.lastname: Sperling
authors.forename: Kevin K
authors.initials: KK
authors.lastname: Wang
authors.forename: Hans
authors.initials: H
authors.lastname: Worthmann
authors.forename: Ronald L
authors.initials: RL
authors.lastname: Hayes
authors.forename: Nico
authors.initials: N
authors.lastname: von Ahsen
authors.forename: Andreas
authors.initials: A
authors.lastname: Kastrup
authors.forename: Andreas
authors.initials: A
authors.lastname: Jeromin
authors.forename: Manfred
authors.initials: M
authors.lastname: Herrmann
mesh_terms: D000368:Aged; D019540:Area Under Curve; D015415:Biomarkers / Q000097:blood; D002545:Brain Ischemia / Q000097:blood* / Q000150:complications / Q000188:drug therapy*; D000068817:Epoetin Alfa; D004921:Erythropoietin / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use; D020521:Stroke / Q000097:blood* / Q000150:complications / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D018696:Neuroprotective Agents; D011994:Recombinant Proteins; D004921:Erythropoietin; D000068817:Epoetin Alfa