Following traumatic brain injury (TBI), the cytoskeletal protein α-II-spectrin is proteolyzed by calpain and caspase-3 to signature breakdown products. To determine whether α -II-spectrin proteolysis is a potentially reliable biomarker for TBI in humans, the present study (1) examined levels of spectrin breakdown products (SBDPs) in cerebrospinal fluid (CSF) from adults with severe TBI and (2) examined the relationship between these levels, severity of injury, and clinical outcome. This prospective case control study enrolled 41 patients with severe TBI, defined by a Glasgow Coma Scale (GCS) score of ≤8, who underwent intraventricular intracranial pressure monitoring. Patients without TBI requiring CSF drainage for other medical reasons served as controls. Ventricular CSF was sampled from each patient at 6, 12, 24, 48, 72, 96, and 120 h following TBI and analyzed for SBDPs. Outcome was assessed using the Glasgow Outcome Score (GOS) 6 months after injury. Calpain and caspase-3 mediated SBDP levels in CSF w...

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Clinical Significance of αII-Spectrin Breakdown Products in Cerebrospinal Fluid after Severe Traumatic Brain Injury

Background
Several studies have suggested that neuron-specific enolase (NSE) in serum may be a biomarker of traumatic brain injury. However, whether serum NSE levels correlate with outcomes remains unclear. The purpose of this review was to evaluate the prognostic value of serum NSE protein after traumatic brain injury.

https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0106680&type=printable

The Prognostic Value of Serum Neuron-Specific Enolase in Traumatic Brain Injury: Systematic Review and Meta-Analysis

Over the past five decades, those interested in markers of radiation effect have focused primarily on tumor response. More recently, however, the view has broadened to include irradiated normal tissues—markers that predict unusual risk of side-effects, prognosticate during the prodromal and therapeutic phases, diagnose a particular toxicity as radiation-related, and, in the case of bioterror, allow for tissue-specific biodosimetry. Currently, there are few clinically useful radiation-related biomarkers. Notably, levels of some hormones such as thyroid-stimulating hormone (TSH) have been used successfully as markers of dysfunction, indicative of the need for replacement therapy, and for prevention of cancers. The most promising macromolecular markers are cytokines: TGFβ, IL-1, IL-6, and TNFα being lead molecules in this class as both markers and targets for therapy. Genomics and proteomics are still in nascent stages and are actively being studied and developed.

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Molecular markers of radiation-related normal tissue toxicity

Elevated serum neuron-specific enolase levels are correlated with brain cell damage. Low scores according to Glasgow Coma Scale are also considered as serious poor prognostic factor. The aims of the study were to investigate whether there is a correlation between the two measurements in patients with traumatic brain injury and whether serum neuron-specific enolase levels have potential as a screening test to predict outcome. A total of 169 consecutive patients with traumatic brain injury admitted to our clinic between 2002 and 2005 are included in this study. Those patients, who had any major health problem before trauma, were excluded from the study. However, patients with isolated head injury were included in the study. Serial serum neuron-specific enolase concentrations taken at the first 2, 24, and 48 h after traumatic brain injury were analyzed. A computed tomography was performed on each patient on admission. Their Glasgow Coma Scale scores were recorded serially. The relationship between Glasgow Coma Scale scores and the serum neuron-specific enolase levels were assessed by statistical methods. There was a significant negative correlation between the serum neuron-specific enolase levels and Glasgow Coma Scale scores. The levels of neuron-specific enolase were significantly higher in the patients who died in 30 days after trauma and whose scores were lower than or equal to 8 points in Glasgow Coma Scale. Although there are several serious limitations of the use of neuron-specific enolase as a biomarker in traumatic brain injury (i.e., hypoperfusion, extracranial trauma, bleeding, liver, or kidney damage also increase the level of neuron-specific enolase), its concentrations may be useful as a practical and helpful screening test to identify neurotrauma patients who are at increased risk and may provide supplementary estimation with radiological and clinical findings.

Serum neuron-specific enolase as a predictor of short-term outcome and its correlation with Glasgow Coma Scale in traumatic brain injury

Traumatic brain injury (TBI) and hypoxic ischemic encephalopathy (HIE) are leading causes of morbidity and mortality in children. Several studies over the past several years have evaluated the use of serum biomarkers to predict outcome after pediatric brain injury. These studies have all used simple point estimates such as initial and peak biomarker concentrations to predict outcome. However, this approach does not recognize patterns of change over time. Trajectory analysis is a type of analysis which can capture variance in biomarker concentrations over time and has been used with success in the social sciences. We used trajectory analysis to evaluate the ability of the serum concentrations of 3 brain-specific biomarkers - S100B, neuron-specific enolase (NSE) and myelin basic protein (MBP) - to predict poor outcome (Glasgow Outcome Scale scores 3-5) after pediatric TBI and HIE. Clinical and biomarker data from 100 children with TBI or HIE were evaluated. For each biomarker, we validated 2-, 3- and 4-group models for outcome prediction, using sensitivity and specificity. For S100B, the 3-group model predicted poor outcome with a sensitivity of 59% and specificity of 100%. For NSE, the 3-group model predicted poor outcome with a sensitivity of 48% and specificity of 98%. For MBP, the 3-group model predicted poor outcome with a sensitivity of 73% and specificity of 61%. Thus, when the models predicted a poor outcome, there was a very high probability of a poor outcome. In contrast, 17% of subjects with a poor outcome were predicted to have a good outcome by all 3 biomarker trajectories. These data suggest that trajectory analysis of biomarker data may provide a useful approach for predicting outcome after pediatric brain injury.

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Trajectory analysis of serum biomarker concentrations facilitates outcome prediction after pediatric traumatic and hypoxemic brain injury.

OBJECTIVE To study the association between serum neuron-specific enolase (NSE) and the extent of brain damage and the outcome after acute traumatic brain injury (TBI). METHODS The release patterns of serum NSE in 78 patients after acute TBI were analyzed by using the enzyme linked immunosorbent assay. The levels of NSE were compared with Glasgow coma scale, the category of brain injury and the outcome after 6 months of injury. RESULTS There were different NSE values in patients with minor (12.96 microg/L+/-2.39 microg/L), moderate (23.44 microg/L+/-5.33 microg/L) and severe brain injury (42.68 microg/L+/-4.57 microg/L). After severe TBI, the concentration of NSE in patients with epidural hematomas was 13.38 microg/L+/-4.01 microg/L, 24.03 microg/L+/-2.85 microg/L in brain contusion without surgical intervention group, 55.20 microg/L+/-6.35 microg/L in brain contusion with surgical intervention group, and 83.85 microg/L+/-15.82 microg/L in diffuse brain swelling group. There were close correlations between NSE values and Glasgow coma scale (r=-0.608, P<0.01) and the extent of brain injury (r=0.75, P<0.01). Patients with poor outcome had significantly higher initial and peak NSE values than those with good outcome (66.40 microg/L+/-9.46 microg/L, 94.24 microg/L+/-13.75 microg/L vs 32.16 microg/L+/-4.21 microg/L, 34.08 microg/L+/-4.40 microg/L, P<0.01, respectively). Initial NSE values were negatively related to the outcome (r=-0.501, P<0.01). Most patients with poor outcomes had persisting or secondary elevated NSE values. CONCLUSIONS Serum NSE is one of the valuable neurobiochemical markers for assessment of the severity of brain injury and outcome prediction.

Wei Guan

Papers

Significance of serum neuron-specific enolase in patients with acute traumatic brain injury.