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Front Neurol. 2017 Jul 3;8:300. doi: 10.3389/fneur.2017.00300. eCollection 2017.

Serial Sampling of Serum Protein Biomarkers for Monitoring Human Traumatic Brain Injury Dynamics: A Systematic Review.

Author information

1
Division of Neurosurgery, Department of Clinical Neurosciences, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom.
2
Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
3
Division of Anaesthesia, Department of Medicine, University of Cambridge, Cambridge, United Kingdom.
4
Department of Surgery, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada.
5
Clinician Investigator Program, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada.
6
Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, Messina, Italy.
7
Szentagothai Research Centre, University of Pecs, Pecs, Hungary.
8
Department of Neurosurgery, University of Pecs, Pecs, Hungary.
9
MTA-PTE Clinical Neuroscience MR Research Group, Pecs, Hungary.
10
Wolfson Brain Imaging Centre, Department of Clinical Neurosciences, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom.
11
Section of Perioperative Medicine and Intensive Care, Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.

Abstract

BACKGROUND:

The proteins S100B, neuron-specific enolase (NSE), glial fibrillary acidic protein (GFAP), ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), and neurofilament light (NF-L) have been serially sampled in serum of patients suffering from traumatic brain injury (TBI) in order to assess injury severity and tissue fate. We review the current literature of serum level dynamics of these proteins following TBI and used the term "effective half-life" (t1/2) in order to describe the "fall" rate in serum.

MATERIALS AND METHODS:

Through searches on EMBASE, Medline, and Scopus, we looked for articles where these proteins had been serially sampled in serum in human TBI. We excluded animal studies, studies with only one presented sample and studies without neuroradiological examinations.

RESULTS:

Following screening (10,389 papers), n = 122 papers were included. The proteins S100B (n = 66) and NSE (n = 27) were the two most frequent biomarkers that were serially sampled. For S100B in severe TBI, a majority of studies indicate a t1/2 of about 24 h, even if very early sampling in these patients reveals rapid decreases (1-2 h) though possibly of non-cerebral origin. In contrast, the t1/2 for NSE is comparably longer, ranging from 48 to 72 h in severe TBI cases. The protein GFAP (n = 18) appears to have t1/2 of about 24-48 h in severe TBI. The protein UCH-L1 (n = 9) presents a t1/2 around 7 h in mild TBI and about 10 h in severe. Frequent sampling of these proteins revealed different trajectories with persisting high serum levels, or secondary peaks, in patients with unfavorable outcome or in patients developing secondary detrimental events. Finally, NF-L (n = 2) only increased in the few studies available, suggesting a serum availability of >10 days. To date, automated assays are available for S100B and NSE making them faster and more practical to use.

CONCLUSION:

Serial sampling of brain-specific proteins in serum reveals different temporal trajectories that should be acknowledged. Proteins with shorter serum availability, like S100B, may be superior to proteins such as NF-L in detection of secondary harmful events when monitoring patients with TBI.

KEYWORDS:

S100B; biomarkers; glial fibrillary acidic protein; neurofilament light; neuron-specific enolase; serum; traumatic brain injury; ubiquitin carboxy-terminal hydrolase L1

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