Introduction: Glial fibrillary acidic protein (GFAP) may serve as a serum marker of traumatic brain injury (TBI) that can be used to monitor biochemical changes in patients and gauge the response to treatment. However, the temporal profile of serum GFAP in the acute period of brain injury and the associated utility for outcome prediction has not been elucidated.Methods: We conducted a prospective longitudinal cohort study of consecutive severe TBI patients in a local tertiary neurotrauma center in Shanghai, China, between March 2011 and September 2014. All patients were monitored and managed with a standardized protocol with inclusion of hypothermia and other intensive care treatments. Serum specimens were collected on admission and then daily for the first 5 days. GFAP levels were measured using enzyme-linked immunosorbent assay techniques. Patient outcome was assessed at 6 months post injury with the Glasgow Outcome Scale and further grouped into death versus survival and unfavorable versus favorable.Results: A total of 67 patients were enrolled in the study. The mean time from injury to admission was 2.6 hours, and the median admission Glasgow Coma Scale score was 6. Compared with healthy subjects, patients with severe TBI had increased GFAP levels on admission and over the subsequent 5 days post injury. Serum GFAP levels showed a gradual reduction from admission to day 3, and then rebounded on day 4 when hypothermia was discontinued with slow rewarming. GFAP levels were significantly higher in patients who died or had an unfavorable outcome across all time points than in those who were alive or had a favorable outcome. Results of receiver operating characteristic curve analysis indicated that serum GFAP at each time point could predict neurological outcome at 6 months. The areas under the curve for GFAP on admission were 0.761 for death and 0.823 for unfavorable outcome, which were higher than those for clinical variables such as age, Glasgow Coma Scale score, and pupil reactions.Conclusions: Serum GFAP levels on admission and during the first 5 days of injury were increased in patients with severe TBI and were predictive of neurological outcome at 6 months.

Traumatic brain injury (TBI) is a major health and socioeconomic problem worldwide with a high rate of death and long-term disability. Previous studies have summarized evidence from large-scale randomized trials, finding no intervention showing convincing efficacy for acute TBI management. The present empirical study set out to assess another crucial component of evidence base-systematic review, which contributes a lot to evidence-based health care, in terms of clinical issues, methodological aspects, and implication for practice and research. A total of 44 systematic reviews pertaining to therapeutic interventions for acute TBI were identified through electronic database searching, clinical guideline retrieval, and expert consultation, of which 21 were published in Cochrane Library and 23 in peer-reviewed journals. Their methodological quality was generally satisfactory, with the median Overview Quality Assessment Questionnaire score of 5.5 (interquartile range 2–7). Cochrane reviews are of better quality than regular journal reviews. Twenty-nine high-quality reviews provided no conclusive evidence for the investigated 22 interventions except for an adverse effect of corticosteroids. Less than one-third of the component trials were reported with adequate allocation concealment. Additionally other methodological flaws in design—for example, ignoring heterogeneity among the TBI population—also contributed to the failure of past clinical research. Based on the above findings, evidence from both systematic reviews and clinical trials does not fully support current management of acute TBI. Translating from laboratory success to clinical effect remains an unique challenge. Accordingly it may be the time to rethink the way in future practice and clinical research in TBI.

Scientific efforts continue to concentrate on elucidating the complex molecular mechanisms underlying traumatic brain injury (TBI), and recent reports suggest that epigenetic regulation including long non-coding RNA (lncRNA) is involved. The present study aimed to investigate the plasma concentration of a long non-coding RNA, named growth arrest-specific 5 (GAS5), in a group of 45 patients with severe TBI (sTBI), and to analyze the correlations of GAS5 with TBI onset, injury severity, systemic inflammation, and early outcome of the patients. It was found that plasma GAS5 levels were substantially increased in sTBI patients compared with the relative controls (p < 0.001). Further, significantly higher expression of plasma GAS5 was observed in patients with a Glasgow Coma Scale (GCS) score of less than five (p = 0.002) or unfavorable outcome at discharge (p < 0.001). Circulating GAS5 expression had a negative correlation with GCS score (r = −0.406, p = 0.006), and positive correlations with white blood cell count (r = 0.473, p = 0.001), neutrophil count (r = 0.502, p < 0.001), and neutrophil/lymphocyte ratio (NLR) (r = 0.398, p = 0.007). Univariate and multivariate logistic regression analyses revealed that GCS score (OR = 0.318, 95% CI 0.132–0.767, p = 0.011) and GAS5 (OR = 2.771, 95% CI 1.025–7.494, p = 0.045) were the two independent predictors for early outcome of patients. The receiver operating characteristic (ROC) curves showed good prognostic values of GCS score (AUC = 0.856, 95% CI: 0.719–0.943) and GAS5 expression (AUC = 0.798, 95% CI: 0.651–0.903). Importantly, the combined use of them can improve the prognostic ability of TBI with an AUC of 0.895 (95% CI: 0.767–0.966). Collectively, our study indicated that the levels of lncRNA GAS5 in circulation were elevated following severe TBI and correlated well with injury severity and inflammatory parameters. In addition, GAS5 as well as GCS scores may have the potential to predict the early outcome of TBI patients.