Marker Of Traumatic Brain Injury Research Articles

Serum metabolomic markers for traumatic brain injury: a mouse model

Traumatic brain injury (TBI) is physical injury to brain tissue that temporarily or permanently impairs brain function. Evaluate the use of metabolomics for the development of biomarkers of TBI for the diagnosis and timing of injury onset. A validated model of closed injury TBI was employed using 10 TBI mice and 8 sham operated controls. Quantitative LC–MS/MS metabolomic analysis was performed on the serum. Thirty-six (24.0 %) of 150 metabolites were altered with TBI. Principal component analysis (PCA) and Partial least squares discriminant analysis (PLS-DA) analyses revealed clear segregation between TBI versus control sera. The combination of methionine sulfoxide and the lipid PC aa C34:4 accurately diagnosed TBI, AUC (95 % CI) 0.85 (0.644–1.0). A combination of metabolite markers were highly accurate in distinguishing early (4 h post TBI) from late (24 h) TBI: AUC (95 % CI) 1.0 (1.0–1.0). Spermidine, which is known to have an antioxidant effect and which is known to be metabolically disrupted in TBI, was the most discriminating biomarker based on the variable importance ranking in projection (VIP) plot. Several important metabolic pathways were found to be disrupted including: pathways for arginine, proline, glutathione, cysteine, and sphingolipid metabolism. Using serum metabolomic analysis we were able to identify novel putative serum biomarkers of TBI. They were accurate for detecting and determining the timing of TBI. In addition, pathway analysis provided important insights into the biochemical mechanisms of brain injury. Potential clinical implications for diagnosis, timing, and monitoring brain injury are discussed.

Glial fibrillary acidic protein as a biomarker in severe traumatic brain injury patients: a prospective cohort study.

IntroductionGlial 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.MethodsWe 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.ResultsA 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.ConclusionsSerum 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.

Role of apolipoprotein E polymorphism as a prognostic marker in traumatic brain injury and neurodegenerative disease: a critical review.

OBJECT The difference in course and outcome of several neurodegenerative conditions and traumatic injuries of the nervous system points toward a possible role of genetic and environmental factors as prognostic markers. Apolipoprotein E (Apo-E), a key player in lipid metabolism, is recognized as one of the most powerful genetic risk factors for dementia and other neurodegenerative diseases. In this article, the current understanding of APOE polymorphism in various neurological disorders is discussed. METHODS The English literature was searched for various studies describing the role of APOE polymorphism as a prognostic marker in neurodegenerative diseases and traumatic brain injury. The wide ethnic distribution of APOE polymorphism was discussed, and the recent meta-analyses of role of APOE polymorphism in multiple diseases were analyzed and summarized in tabular form. RESULTS Results from the review of literature revealed that the distribution of APOE is varied in different ethnic populations. APOE polymorphism plays a significant role in pathogenesis of neurodegeneration, particularly in Alzheimer's disease. APOE ε4 is considered a marker for poor prognosis in various diseases, but APOE ε2 rather than APOE ε4 has been associated with cerebral amyloid angiopathy-related bleeding and sporadic Parkinson's disease. The role of APOE polymorphism in various neurological diseases has not been conclusively elucidated. CONCLUSIONS Apo-E is a biomarker for various neurological and systemic diseases. Therefore, while analyzing the role of APOE polymorphism in neurological diseases, the interpretation should be done after adjusting all the confounding factors. A continuous quest to look for associations with various neurological diseases and wide knowledge of available literature are required to improve the understanding of the role of APOE polymorphism in these conditions and identify potential therapeutic targets.

Should an increase in cerebral neurochemicals following head kicks in full contact karate influence return to play?

Cerebral neurochemicals are markers of traumatic brain injury (TBI). The aim of the study was to determine whether kicks to the head (KTH) in full contact karate significantly increased serum concentrations of protein S-100B, and neurone specific enolase (NSE). Kicks to the body (KTB) were also quantified to asses muscle tissue injury. Muscle damage was assessed by analysis of serum total creatine kinase (CK). Twenty-four full contact karate practitioners were observed and filmed during actual competition and divided into two main groups post event: (1) Kicks to the head and body group (KTH): n = 12; mean ± SD; age, 30.4 ± 6.7 years; height, 1.74 ± 0.1 m; weight, 79.1 ± 2.1 kg; and (2): Kicks to the body group (KTB): n = 12; mean ± SD; age, 28.2 ± 6.5 years; height, 1.75 ± 0.1 m; weight, 79.2 ± 1.7 kg. The KTH group received direct kicks to the head, while group KTB received kicks and punches to the body. Blood samples were taken before and immediately post-combat for analysis of serum S-100B, NSE, CK and cardiac troponin. Significant increases in serum concentrations of S-100B (0.12 ± 0.17 vs. 0.37 ± 0.26, µg.L(-1)) and NSE (11.8 ± 4.1 vs. 20.2 ± 9.1 ng.mL(-1)) were encountered after combat in the KTH group and CK (123 ± 53 vs. 184 ± 103 U.L(-1)) in the KTB group (all P <0.05). Head kicks in full contact karate cause elevation of neurochemical markers associated with damaged brain tissue. The severity of injury is related to the early post-traumatic release of protein S-100B and NSE. The early kinetics and appearance post injury can reflect intracranial pathology, and suggest S-100B and NSE are extremely sensitive prognostic markers of TBI.

Fluid markers of traumatic brain injury.

Traumatic brain injury (TBI) occurs when an external force traumatically injures the brain. Whereas severe TBI can be diagnosed using a combination of clinical signs and standard neuroimaging techniques, mild TBI (also called concussion) is more difficult to detect. This is where fluid markers of injury to different cell types and subcellular compartments in the central nervous system come into play. These markers are often proteins, peptides or other molecules with selective or high expression in the brain, which can be measured in the cerebrospinal fluid or blood as they leak out or get secreted in response to the injury. Here, we review the literature on fluid markers of neuronal, axonal and astroglial injury to diagnose mild TBI and to predict clinical outcome in patients with head trauma. We also discuss chronic traumatic encephalopathy, a progressive neurodegenerative disease in individuals with a history of multiple mild TBIs in a biomarker context. This article is part of a Special Issue entitled 'Traumatic Brain Injury'.

Depletion of Brain Docosahexaenoic Acid Impairs Recovery from Traumatic Brain Injury

Omega-3 fatty acids are crucial for proper development and function of the brain where docosahexaenoic acid (DHA), the primary omega-3 fatty acid in the brain, is retained avidly by the neuronal membranes. We investigated the effect of DHA depletion in the brain on the outcome of traumatic brain injury (TBI). Pregnant mice were put on an omega-3 fatty acid adequate or deficient diet from gestation day 14 and the pups were raised on the respective diets. Continuation of this dietary regime for three generations resulted in approximately 70% loss of DHA in the brain. Controlled cortical impact was delivered to both groups of mice to produce severe TBI and the functional recovery was compared. Compared to the omega-3 adequate mice, the DHA depleted mice exhibited significantly slower recovery from motor deficits evaluated by the rotarod and the beam walk tests. Furthermore, the DHA deficient mice showed greater anxiety-like behavior tested in the open field test as well as cognitive deficits evaluated by the novel object recognition test. The level of alpha spectrin II breakdown products, the markers of TBI, was significantly elevated in the deficient mouse cortices, indicating that the injury is greater in the deficient brains. This observation was further supported by the reduction of NeuN positive cells around the site of injury in the deficient mice, indicating exacerbated neuronal death after injury. These results suggest an important influence of the brain DHA status on TBI outcome.

The inflammatory cellular constituents of foetal and infant leptomeninges: a survey of hospital-based autopsies without trauma

ObjectivesNotwithstanding the lack of definitive evidence from studies conducted to date, inflammatory infiltrates and iron deposition in the leptomeninges are routinely used as forensic markers of traumatic brain injury. We investigated the presence of these forensic markers of trauma in neonates and infants, with the objective of determining their suitability for use in forensic cases.MethodsLeptomeninges derived from non-traumatic deaths were studied. Thirty-three cases were divided into groups 1 and 2, according to set age groups. Inflammatory cells and iron in these groups were quantified.ResultsCD45, CD68 and CD163 positive inflammatory cells were identified in the leptomeninges of sections of the cerebellum, brain stem and cortex of all 33 cases of non-traumatic infant deaths surveyed in this study. There were no significant differences between the two groups. Iron was found in the leptomeninges in several cases, even those without recent haemorrhage. Overall within the two subgroups, the numbers of inflammatory cells and iron containing cells were not significantly different.ConclusionThese findings demonstrate that inflammatory cells and iron in the leptomeninges can be found in natural and non-traumatic conditions. Further, two cases with no reported neuropathology demonstrated the presence of inflammatory cells and iron. Thus, cautious interpretation of the presence of inflammatory cells and iron containing cells in forensic paediatric cases is recommended.

S100B and NSE as Useful Postmortem Biochemical Markers of Traumatic Brain Injury in Autopsy Cases

Postmortem analysis of relevant biomarkers might aid in characterizing causes of death and survival times in legal medicine. However, there are still no sufficiently established results of practical postmortem biochemical investigations in cases of traumatic brain injury (TBI). The two biomarkers--S100 protein subunit B (S100B) and neuronal specific enolase (NSE)--could be of special interest. Therefore, the aim of the present study was to investigate changes in their postmortem levels for further determination of brain damage in TBI. In 17 cases of TBI (average age, 58 years) and in 23 controls with different causes of death (average age, 59 years), serum and cerebrospinal fluid (CSF) samples were analyzed with a chemiluminescence immunoassay for marker expression. An increase in serum S100B, as well as a subsequent decrease after survival times>4 days, were detected in TBI cases (p<0.01). CSF NSE values >6,000 ng/mL and CSF S100B levels >10,000 ng/mL seem to indicate a TBI survival time of at least 15 min (p<0.01). It is of particular interest that CSF S100B levels (p<0.01) and serum S100B levels (p<0.05) as well as CSF NSE values (p<0.01) were significantly higher in TBI cases in comparison to the controls, especially when compared with fatal non-head injuries. In conclusion, the present findings emphasize that S100B and NSE are useful markers in postmortem biochemistry in cases of suspected TBI. Further, S100B may be helpful to estimate the survival time of fatal injuries in legal medicine.

GFAP-BDP as an Acute Diagnostic Marker in Traumatic Brain Injury: Results from the Prospective Transforming Research and Clinical Knowledge in Traumatic Brain Injury Study

Reliable diagnosis of traumatic brain injury (TBI) is a major public health need. Glial fibrillary acidic protein (GFAP) is expressed in the central nervous system, and breakdown products (GFAP-BDP) are released following parenchymal brain injury. Here, we evaluate the diagnostic accuracy of elevated levels of plasma GFAP-BDP in TBI. Participants were identified as part of the prospective Transforming Research And Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) Study. Acute plasma samples (<24 h post-injury) were collected from patients presenting with brain injury who had CT imaging. The ability of GFAP-BDP level to discriminate patients with demonstrable traumatic lesions on CT, and with failure to return to pre-injury baseline at 6 months, was evaluated by the area under the receiver operating characteristic curve (AUC). Of the 215 patients included for analysis, 83% had mild, 4% had moderate, and 13% had severe TBI; 54% had acute traumatic lesions on CT. The ability of GFAP-BDP level to discriminate patients with traumatic lesions on CT as evaluated by AUC was 0.88 (95% confidence interval [CI], 0.84-0.93). The optimal cutoff of 0.68 ng/mL for plasma GFAP-BDP level was associated with a 21.61 odds ratio for traumatic findings on head CT. Discriminatory ability of unfavorable 6 month outcome was lower, AUC 0.65 (95% CI, 0.55-0.74), with a 2.07 odds ratio. GFAP-BDP levels reliably distinguish the presence and severity of CT scan findings in TBI patients. Although these findings confirm and extend prior studies, a larger prospective trial is still needed to validate the use of GFAP-BDP as a routine diagnostic biomarker for patient care and clinical research. The term "mild" continues to be a misnomer for this patient population, and underscores the need for evolving classification strategies for TBI targeted therapy. (ClinicalTrials.gov number NCT01565551; NIH Grant 1RC2 NS069409).

Role of Phosphorylated Neurofilament H as a diagnostic and prognostic marker in traumatic brain injury

Background and purposeOne of the main drawbacks in the management of patients with traumatic brain injuries (TBI) is the absence of a widely available and rapid diagnostic test. The objective of our study was to assess whether Phosphorylated Neurofilament H (pNF-H) might provide useful diagnostic information as an indication of axonal injury in the early evaluation of such patients and whether levels of the pNF-H correlated with different clinical variables. MethodsA total of 30 patients presenting to the critical care department of Cairo University diagnosed with traumatic brain injury were prospectively studied. Blood samples for pNF-H were assayed on admission and after 7 days. Neurofilament levels correlated with Glasgow coma scale and CT findings on admission and after 7 days. Rankin score at 3 months was used to detect the degree of disability. ResultsPhosphorylated Neurofilament H levels showed a negative correlation with GCS on admission and after 7 days in traumatic brain injury; hence higher neuromarker levels were associated with lower GCS on admission and after 7 days. There was a negative correlation between neurofilament levels and Marshal CT scores on admission and after 7 days (r = 0.56.0.4) hence higher neurofilament levels correlated with worse CT findings. Patients who died or had the greatest Rankin 6 and 5 after 3 months had the highest levels of pNF-H on admission and after 7 days. The cut off level of pNF-H to detect death and disability was 35 pg/ml on admission (sensitivity 82%, specificity 78%) and was 11 pg/ml after 7 days (sensitivity87%, and specificity 92%). ConclusionPhosphorylated Neurofilament H can be used as a diagnostic and prognostic marker in patients with TBI as seen by the presence of significant correlations between the marker levels and different clinical and radiological tools.

Effect of slosh mitigation on histologic markers of traumatic brain injury

Helmets successfully prevent most cranial fractures and skull traumas, but traumatic brain injury (TBI) and concussions continue to occur with frightening frequency despite the widespread use of helmets on the athletic field and battlefield. Protection against such injury is needed. The object of this study was to determine if slosh mitigation reduces neural degeneration, gliosis, and neuroinflammation. Two groups of 10 adult male Sprague-Dawley rats were subjected to impact-acceleration TBI. One group of animals was fitted with a collar inducing internal jugular vein (IJV) compression prior to injury, whereas the second group received no such collar prior to injury. All rats were killed 7 days postinjury, and the brains were fixed and embedded in paraffin. Tissue sections were processed and stained for markers of neural degeneration (Fluoro-Jade B), gliosis (glial fibrillary acidic protein), and neuroinflammation (ionized calcium binding adapter molecule 1). Compared with the controls, animals that had undergone IJV compression had a 48.7%-59.1% reduction in degenerative neurons, a 36.8%-45.7% decrease in reactive astrocytes, and a 44.1%-65.3% reduction in microglial activation. The authors concluded that IJV compression, a form of slosh mitigation, markedly reduces markers of neurological injury in a common model of TBI. Based on findings in this and other studies, slosh mitigation may have potential for preventing TBI in the clinical population.

Location and Level of Etk Expression in Neurons Are Associated with Varied Severity of Traumatic Brain Injury

BackgroundMuch recent research effort in traumatic brain injury (TBI) has been devoted to the discovery of a reliable biomarker correlating with severity of injury. Currently, no consensus has been reached regarding a representative marker for traumatic brain injury. In this study, we explored the potential of epithelial/endothelial tyrosine kinase (Etk) as a novel marker for TBI.Methodology/Principal FindingsTBI was induced in Sprague Dawley (SD) rats by controlled cortical impact. Brain tissue samples were analyzed by Western blot, Q-PCR, and immunofluorescence staining using various markers including glial fibrillary acidic protein, and epithelial/endothelial tyrosine kinase (Etk). Results show increased Etk expression with increased number and severity of impacts. Expression increased 2.36 to 7-fold relative to trauma severity. Significant upregulation of Etk appeared at 1 hour after injury. The expression level of Etk was inversely correlated with distance from injury site. Etk and trauma/inflammation related markers increased post-TBI, while other tyrosine kinases did not.Conclusion/SignificanceThe observed correlation between Etk level and the number of impacts, the severity of impact, and the time course after impact, as well as its inverse correlation with distance away from injury site, support the potential of Etk as a possible indicator of trauma severity.

Biological markers and severe head trauma. Where are we?

AbstractTraumatic brain injury (TBI) constitutes a major health and socioeconomic problem throughout the world. Despite the significant advances in neuroradiology and cerebral monitoring it is still difficult to measure the degree of primary brain injury and continuing secondary damage with Glasgow Coma Scale score or the initial computed tomography. Predicting prognosis of TBI patients in early stages has a vital importance and is difficult in some instances. The present review shows that there has been an increasing interest in biochemical markers for traumatic brain injury during the last years. The potential correlation of markers with injury and outcome measures in severe head injury is promising.

Serum Levels of Biochemical Markers of Traumatic Brain Injury

Background. A biomarker would be valuable in the diagnosis, risk stratification and prognosis of patients with traumatic brain injury (TBI). Methods. We measured serum levels of S-100β, neuron specific enolase (NSE) and myelin basic protein (MBP) in 50 TBI subjects, and 50 age and gender matched controls. Patients were recruited within 6 hours of the initial injury, they had an initial Glasgow Coma Scale (GCS) score of 14 or less, or a GCS score of 15 with witnessed loss of consciousness (LOC) or amnesia. Results. S-100β, NSE and MBP levels were significantly higher in TBI subjects than in control subjects (P&lt;0.001 for S-100β and NSE; P=0.009 for MBP). Initial S-100β levels were significantly higher in TBI subjects who had not retuned to normal activities 2 weeks following their injury than in TBI subjects who had retuned to normal activities (P=0.022). MBP levels were higher in TBI subjects with positive findings on the baseline CT scan than in CT-negative subjects (P=0.007). Conclusions. S-100β, NSE and MBP may be present in the sera of TBI subjects in elevated quantities relative to controls. S-100β may aid in predicting short-term outcome in TBI subjects.

Endothelial progenitor cells correlate with clinical outcome of traumatic brain injury

Endothelial progenitor cells play an active role in vascular repair and revascularization of tissue damaged by traumatic, inflammatory, and ischemic injures. We correlate the changes in circulating endothelial progenitor cells with the severity of traumatic brain injury. The study is designed to investigate the endothelial progenitor cell mobilization after injury and a potential use of circulating endothelial progenitor cells as a prognostic marker for evaluating trauma severity and clinical outcomes. A prospective cohort study conducted in two neurosurgical intensive care units of Tianjin Medical University General Hospital and Tianjin Huanhu Hospital (Tianjin, China). Patients with traumatic brain injury and age- and gender-matched healthy controls. None. Changes in the levels of circulating endothelial progenitor cells were monitored for up to 21 days in 84 patients with traumatic brain injury. Results were correlated with the clinical assessment of injury severity as determined by the Glasgow Coma Scale. The level of circulating endothelial progenitor cells was found to be suppressed 24-48 hrs after injury but rapidly increased, reaching the highest at days 5-7 post-trauma. Circulating endothelial progenitor cells in patients with improved Glasgow Coma Scale scores were significantly higher than those with deteriorated conditions and remained persistently low in patients who died of trauma. The results suggest that the level of circulating endothelial progenitor cells correlates with the clinical severity and outcome of traumatic brain injury and may offer potential as a prognostic marker for traumatic brain injury. A long-term follow-up of these patients is ongoing.

Biochemical markers of traumatic brain injury.

Background: Currently used clinical and radiological findings of particularly mild traumatic brain injury have limited diagnostic and prognostic value. Methods and results: We conducted a systematic review of selected primary clinical studies on biochemical markers of traumatic brain injury in the last 10 years, using an electronic search of the National Library of Medicine’s database MEDLINE. The most explored and clinically relevant biochemical markers of acute brain injury are protein S100B, neuron-specific enolase and glial fibrillary acidic protein. In addition, novel markers such as spectrin breakdown product, c-tau and amiloid-b are presented. Based on clinical trials, the rationale for their use in the context of severity of traumatic brain injury is outlined. Conclusions: Measurement of biochemical markers of brain injury should be introduced in the clinical management of mild traumatic brain injury. The predictive value of current clinical and radiological findings can be markedly improved by the determination of biochemical markers in mild and severe traumatic brain injury.

Hospital Mortality of Patients with Severe Traumatic Brain Injury is Associated with Serum PTX3 Levels

Traumatic brain injury (TBI) is a worldwide cause of morbidity and mortality. Pentraxin 3 (PTX3) is a humoral component of the innate immune system which has been studied as a marker of inflammatory, infections or cardiovascular pathologies. To investigate the association between serum levels of PTX3 and the hospital mortality of patients with severe TBI. The independent association between serum PTX3 levels after severe TBI (Glasgow Coma Scale, GCS ≤ 8) and hospital mortality was analyzed in a prospective study of 83 consecutive patients by a multiple logistic regression analysis. The leukocyte count in the same sample was analyzed as another marker of inflammatory response. The mean age of patients was 35 years and 85% were male. Serum PTX3 levels were determined 18.0 (SD ± 17.0) h after TBI. Patients who died showed a mean serum PTX3 level of 9.95 μg/ml (SD ± 6.42) in comparison to 5.46 μg/ml (SD ± 4.87) of the survivor group (P = 0.007). Elevated serum PTX3 levels remain significantly associated with mortality (P = 0.04) in the subset of patients with isolated TBI (n = 34). There were no differences in the leukocytes count measured in the same blood sample used for PTX3 determination in survivors and non-survivors (P = 0.56). The final multiple logistic regression model including age, pupillary examination, GCS, associated trauma, and PTX3 levels shows that serum levels of PTX3 which were higher than 10 μg/ml were independently associated with the patients mortality (adjusted OR 3.06, CI 95% 1.03-9.15, P = 0.04). Serum PTX3 levels after severe TBI are independently associated with higher hospital mortality and may be a useful marker of TBI and its prognosis.

Can S-100B serum protein help to save cranial CT resources in a peripheral trauma centre? A study and consensus paper

BackgroundCranial CT (CCT) is the gold standard to rule out traumatic brain injury. The serum level of the protein S-100B has recently been proposed as promising marker of traumatic brain...

Pediatric Traumatic Brain Injury: The Utility of Beta-Natriuretic Peptide

According to the literature, serum beta-natriuretic peptide (BNP) levels have been shown to increase in adult trauma patients, specifically for those with traumatic brain injury and in those with intracranial hemorrhage. It has been suggested that BNP levels may be an ideal serum marker for traumatic brain injury. It may save time and radiation if the levels correlated with head computed tomography (CT) scan findings, especially for pediatric patients who have higher radiation risks. We hypothesized that serum BNP levels would be elevated in patients with intracranial bleeding on head CT. Serum BNP levels were drawn from 95 consecutive "Level I status" pediatric trauma patients immediately on presentation to the emergency department. These patients had high impact mechanisms, were altered, or were physiologically unstable. The findings of head CTs were recorded. Patients were subsequently divided into a negative bleed or positive bleed group. Clinical data such as Glasgow Coma Scale, loss of consciousness, and hospital course were collected. Results were compared using Wilcoxon rank sum test and Spearman correlation coefficients. BNP levels did not increase significantly in the positive bleed group (n = 21) compared with the negative bleed group (n = 74) (p = 0.48). BNP levels did not correlate with loss of consciousness, Glasgow Coma Scale, Injury Severity Score, or hospital stay. BNP levels drawn at the time of the emergency department visit do not seem to be a predictor for intracranial hemorrhage in pediatric trauma patients. A head CT still remains the best diagnostic study for diagnosing intracranial hemorrhage.

A panel of neuron-enriched proteins as markers for traumatic brain injury in humans.

Surrogate markers have enormous potential for contributing to the diagnosis, prognosis, and therapeutic evaluation of acute brain damage, but extensive prior study of individual candidates has not yielded a biomarker in widespread clinical practice. We hypothesize that a panel of neuron-enriched proteins measurable in cerebrospinal fluid (CSF) and blood should vastly improve clinical evaluation and therapeutic management of acute brain injuries. Previously, we developed such a panel based initially on the study of protein release from degenerating cultured neurons, and subsequently on rodent models of traumatic brain injury (TBI) and ischemia, consisting of 14-3-3beta, 14-3-3zeta, three distinct phosphoforms of neurofilament H, ubiquitin hydrolase L1, neuron-specific enolase, alpha-spectrin, and three calpain- and caspase-derived fragments of alpha-spectrin. In the present study, this panel of 11 proteins was evaluated as CSF and serum biomarkers for severe TBI in humans. By quantitative Western blotting and sandwich immunoassays, the CSF protein levels were near or below the limit of detection in pre-surgical and most normal pressure hydrocephalus (NPH) controls, but following TBI nine of the 11 were routinely elevated in CSF. Whereas different markers peaked coordinately, the time to peak varied across TBI cases from 24-96 h post-injury. In serum, TBI increased all four members of the marker panel for which sandwich immunoassays are currently available: a calpain-derived NH(2)-terminal alpha-spectrin fragment and the three neurofilament H phosphoforms. Our results identify neuron-enriched proteins that may serve as a panel of CSF and blood surrogate markers for the minimally invasive detection, management, mechanistic, and therapeutic evaluation of human TBI.