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

Abstract

BackgroundThe 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 methodsThrough 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.ResultsFollowing 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.ConclusionSerial 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.

Circulating Brain Injury Exosomal Proteins following Moderate-to-Severe Traumatic Brain Injury: Temporal Profile, Outcome Prediction and Therapy Implications

“…The complex and varied biogenesis underpinning the release of circulating exosomal brain injury proteins, along with their potential double-edged role in the contexts of the pathobiology of TBI [21,29], can provide a possible explanation for the observed absence of a correlation between exosomal markers, and injury severity and neurosurgical interventions. Alternatively, we cannot fully rule out an effect of variability in the time interval between blood draw and injury/procedures [30]. Future work is warranted.…”

Importance of GFAP isoform‐specific analyses in astrocytoma

“…These studies suggest that GFAP serum levels are related to brain damage and cell death induced by, in, or near the tumor. This is supported by studies that have linked high GFAP serum levels in patients with traumatic brain injury (Bazarian et al, 2018;Thelin et al, 2017). Increased levels of GFAP positive microparticles can be observed from 7 days up to 7 months after surgery (Sartori et al, 2013), although another study that measured GFAP serum levels 6 weeks after surgery, does not…”

Influence of Blood–Brain Barrier Integrity on Brain Protein Biomarker Clearance in Severe Traumatic Brain Injury: A Longitudinal Prospective Study

“…Biologically, NSE is larger (39 kDa) 71,72 than S100B (9-14 kDa), 73 implications of which could be a swifter movement across body compartments for small proteins and a longer serum half-life for larger proteins. Accordingly, NSE has been shown to exhibit an ''effective half-life'' of up to 48-72 h in serum compared with 24 h for S100B, 74 following severe TBI. This would give a slower decline of NSE blood values than S100B values.…”