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Erythropoietin Does Not Alter Serum Profiles of Neuronal and Axonal Biomarkers After Traumatic Brain Injury: Findings From the Australian EPO-TBI Clinical Trial

Hellewell, SC, Mondello, S, Conquest, A, Shaw, G, Madorsky, I, Deng, JV, Little, L, Kobeissy, F, Bye, N ORCID: 0000-0003-0976-5870, Bellomo, R, Cooper, DJ, Vallance, S, Board, J and Morganti-Kossmann, MC 2017 , 'Erythropoietin Does Not Alter Serum Profiles of Neuronal and Axonal Biomarkers After Traumatic Brain Injury: Findings From the Australian EPO-TBI Clinical Trial' , Critical care medicine , pp. 1-8 , doi:

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Objective: To determine profiles of serum ubiquitin carboxy-terminalhydrolase L1 and phosphorylated neurofilament heavy-chain,examine whether erythropoietin administration reduce their concentrations,and whether biomarkers discriminate between erythropoietinand placebo treatment groups.Design: Single-center, prospective observational study.Setting: A sub-study of the erythropoietin-traumatic brain injuryclinical trial, conducted at the Alfred Hospital, Melbourne, Australia.Patients: Forty-four patients with moderate-to-severe traumaticbrain injury.Interventions: Epoetin alfa 40,000 IU or 1mL sodium chloride 0.9as subcutaneous injection within 24 hours of traumatic brain injury.Measurements and Main Results: Ubiquitin carboxy-terminal hydrolaseL1, phosphorylated neurofilament heavy-chain, and erythropoietinconcentrations were measured in serum by enzyme-linked immunosorbentassay from D0 (within 24hr of injury, prior to erythropoietin/vehicleadministration) to D5. Biomarker concentrations were comparedbetween injury severities, diffuse versus focal traumatic brain injury anderythropoietin or placebo treatment groups. Ubiquitin carboxy-terminalhydrolase L1 peaked at 146.0ng/mL on D0, significantly decreasedto 84.30ng/mL on D1, and declined thereafter. Phosphorylated neurofilamentheavy-chain levels were lowest at D0 and peaked on D5at 157.9ng/mL. D0 ubiquitin carboxy-terminal hydrolase L1 concentrationswere higher in diffuse traumatic brain injury. Peak phosphorylatedneurofilament heavy-chain levels on D3 and D4 correlated withGlasgow Outcome Score–Extended, predicting poor outcome. Erythropoietindid not reduce concentrations of ubiquitin carboxy-terminalhydrolase L1 or phosphorylated neurofilament heavy-chain.Conclusions: Serum ubiquitin carboxy-terminal hydrolase L1 andphosphorylated neurofilament heavy-chain increase after traumaticbrain injury reflecting early neuronal and progressive axonal injury.Consistent with lack of improved outcome in traumatic brain injurypatients treated with erythropoietin, biomarker concentrations andprofiles were not affected by erythropoietin. Pharmacokinetics oferythropoietin suggest that the dose given was possibly too low toexert neuroprotection.

Item Type: Article
Authors/Creators:Hellewell, SC and Mondello, S and Conquest, A and Shaw, G and Madorsky, I and Deng, JV and Little, L and Kobeissy, F and Bye, N and Bellomo, R and Cooper, DJ and Vallance, S and Board, J and Morganti-Kossmann, MC
Keywords: Traumatic brain injury, serum biomarkers, erythropoietin
Journal or Publication Title: Critical care medicine
Publisher: Lippincott Williams & Wilkins
ISSN: 0090-3493
DOI / ID Number:
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Copyright © 2017 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc.

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