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Title: Erythropoietin Does Not Alter Serum Profiles of Neuronal and Axonal Biomarkers After Traumatic Brain Injury: Findings From the Australian EPO-TBI Clinical Trial.
Austin Authors: Hellewell, Sarah C;Mondello, Stefania;Conquest, Alison;Shaw, Gerry;Madorsky, Irina;Deng, Jay V;Little, Lorraine;Kobeissy, Firas;Bye, Nicole;Bellomo, Rinaldo ;Cooper, David J;Vallance, Shirley;Board, Jasmine;Morganti-Kossmann, Maria C
Affiliation: Faculty of Rehabilitation Medicine, University of Alberta, Edmonton, Canada
Department of Surgery, Alfred Hospital, Melbourne, Australia
Department of Medicine, Nursing and Health Sciences, Monash University, Melbourne, Australia
Department of Biomedical and Dental Sciences and Morphofunctional Imaging, Messina University, Messina, Italy
EnCor Biotechnology Inc., Gainesville, FL
Australian New Zealand Intensive Care Research Centre, Melbourne, Australia
Department of Psychiatry and Neuroscience, McKnight Brain Institute, University of Florida, Gainesville, FL
Department of Intensive Care Research, Austin Health, Heidelberg, Victoria, Australia
Department of Intensive Care, Alfred Hospital, Melbourne, Australia
Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia
Department of Child Health, Barrow Neurological Institute, University of Arizona, Phoenix, AZ
Issue Date: Apr-2018
Publication information: Critical Care Medicine 2018; 46(4): 554-561
Abstract: To determine profiles of serum ubiquitin carboxy-terminal hydrolase L1 and phosphorylated neurofilament heavy-chain, examine whether erythropoietin administration reduce their concentrations, and whether biomarkers discriminate between erythropoietin and placebo treatment groups. Single-center, prospective observational study. A sub-study of the erythropoietin-traumatic brain injury clinical trial, conducted at the Alfred Hospital, Melbourne, Australia. Forty-four patients with moderate-to-severe traumatic brain injury. Epoetin alfa 40,000 IU or 1 mL sodium chloride 0.9 as subcutaneous injection within 24 hours of traumatic brain injury. Ubiquitin carboxy-terminal hydrolase L1, phosphorylated neurofilament heavy-chain, and erythropoietin concentrations were measured in serum by enzyme-linked immunosorbent assay from D0 (within 24 hr of injury, prior to erythropoietin/vehicle administration) to D5. Biomarker concentrations were compared between injury severities, diffuse versus focal traumatic brain injury and erythropoietin or placebo treatment groups. Ubiquitin carboxy-terminal hydrolase L1 peaked at 146.0 ng/mL on D0, significantly decreased to 84.30 ng/mL on D1, and declined thereafter. Phosphorylated neurofilament heavy-chain levels were lowest at D0 and peaked on D5 at 157.9 ng/mL. D0 ubiquitin carboxy-terminal hydrolase L1 concentrations were higher in diffuse traumatic brain injury. Peak phosphorylated neurofilament heavy-chain levels on D3 and D4 correlated with Glasgow Outcome Score-Extended, predicting poor outcome. Erythropoietin did not reduce concentrations of ubiquitin carboxy-terminal hydrolase L1 or phosphorylated neurofilament heavy-chain. Serum ubiquitin carboxy-terminal hydrolase L1 and phosphorylated neurofilament heavy-chain increase after traumatic brain injury reflecting early neuronal and progressive axonal injury. Consistent with lack of improved outcome in traumatic brain injury patients treated with erythropoietin, biomarker concentrations and profiles were not affected by erythropoietin. Pharmacokinetics of erythropoietin suggest that the dose given was possibly too low to exert neuroprotection.
DOI: 10.1097/CCM.0000000000002938
ORCID: 0000-0002-1650-8939
PubMed URL: 29278529
Type: Journal Article
Appears in Collections:Journal articles

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