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Objective: This study aims to analyze the risk factors for early postoperative brain injury in patients undergoing cardiovascular surgery and explore the predictive value of transcranial color Doppler (TCCD) and regional cerebral oxygen saturation (rSO 2 ) for detecting early postoperative brain injury in cardiovascular surgery patients., Methods: A total of 55 patients undergoing cardiovascular surgery with cardiopulmonary bypass in Changzhou No.2 The People's Hospital of Nanjing Medical University were included in this study. Neuron-specific enolase (NSE) concentration was measured 24 h after operation. Patients were divided into brain injury (NSE ≥ 16.3 ng/mL) and normal (0 < NSE < 16.3 ng/mL) groups according to the measured NSE concentration. The clinical outcomes between the two groups were compared, including decreased rSO 2 and cerebral blood flow (as measured by TCCD) levels. The risk factors of early postoperative brain injury were analyzed by multivariate logistic regression analysis, and the significant variables were analyzed by receiver operating characteristic (ROC) analysis., Results: A total of 50 patients were included in this study, with 20 patients in the brain injury group and 30 patients in the normal group. Cardiopulmonary bypass time (min) (107 ± 29 vs. 90 ± 28, P = 0.047) and aortic occlusion time (min) (111 (IQR 81-127) vs. 87 (IQR 72-116), P = 0.010) were significantly longer in the brain injury group than in the normal group. Patients in the brain injury group had greater decreased rSO 2 (%) (27.0 ± 7.3 vs. 17.5 ± 6.1, P < 0.001) and cerebral blood flow (%) (44.9 (IQR 37.8-69.2) vs. 29.1 (IQR 12.0-48.2), P = 0.004) levels. Multivariate logistic regression analysis suggested that decreased rSO 2 and cerebral blood flow levels, aortic occlusion time, and history of atrial fibrillation were independent risk factors for early postoperative brain injury (P < 0.05). ROC analysis reported that the best cutoff values for predicting early postoperative brain injury were 21.4% and 37.4% for decreased rSO 2 and cerebral blood flow levels, respectively (P < 0.05)., Conclusion: The decreased rSO 2 and cerebral blood flow levels, aorta occlusion time, and history of atrial fibrillation were independent risk factors for early postoperative brain injury. TCCD and rSO 2 could effectively monitor brain metabolism and cerebral blood flow and predict early postoperative brain injury., (© 2024. The Author(s).)

Background/aim: Postnatal corticosteroids are commonly used to treat bronchopulmonary dysplasia (BPD). We aimed to show whether S100 calcium-binding B (S100B), neuron-specific enolase (NSE), Tau protein or microtubule-associated protein tau (MAPT), and glial fibrillary acid protein (GFAP) levels would provide any evidence of early neurological damage in premature infants receiving postnatal low dose dexamethasone therapy for BPD treatment., Materials and Methods: In this cohort study, 136 preterm infants diagnosed with BPD at ≤32 weeks of gestation formed the study group, and 64 preterm infants formed the control group. NSE, S100B, GFAP, and MAPT levels were first measured before the postnatal corticosteroid treatment in both the patient and the control group on the 28th day and, for a second time, after treatment termination in the patient group., Results: There were significant differences between the measured GFAP, MAPT, and NSE values of the BPD and control groups on the 28th day, whereas there was no significant difference between the measured S100B values of the two groups. There were a statistically significant difference between the NSE values measured on the 28th day and after the treatment within the BPD group, whereas no significant difference existed between the GFAP, MAPT, and S100B values., Conclusion: NSE levels, which indicate brain damage in the early period, increased in preterm babies with BPD who had been administered postnatal dexamethasone., (This work is licensed under a Creative Commons Attribution 4.0 International License.)

Objective: To explore the changes in amplitude-integrated electroencephalography (aEEG), neuron-specific enolase (NSE), and S100B in neonates with brain injury induced by neonatal hyperbilirubinemia (NHB)., Methods: 67 neonates with brain injury induced by NHB admitted to our hospital from March 2016 to October 2018 were included in a brain injury group (BIG), and 82 neonates with NHB but without brain injury in our hospital during the same period were included in a non-BIG. The two groups were compared regarding the rates of normal and abnormal aEEG results., Results: The proportion of normal aEEG results in the BIG was significantly lower than that in the non-BIG, and the proportion of moderately and severely abnormal aEEG results in the BIG were both significantly higher than those in the non-BIG. The BIG showed significantly higher NSE and S100B levels than those of the non-BIG. The ROC curve for predicting prognosis showed that the AUC of aEEG, NSE, S100B, and the combined detection are 0.780, 0.754, 0.743, 0.788. The AUC > 0.700 indicated a good predictive value for the prognosis., Conclusion: The combination of aEEG, NSE, and S100B has good value in diagnosing injury induced by NHB and can predict prognosis moderately well.

In predicting outcomes in patients with acute brain injury, current practice focuses special attention on neuron-specific proteins that reliably reflect the severity of the lesion. Further studies of molecular markers and their specificity and sensitivity could contribute to broadening the understanding of pathophysiological, diagnostic, and prognostic methods, which is vital to reducing the mortality and disability associated with these critical conditions. The purpose of this study was to assess the biomarkers of brain lesions and their correlative relations with the integral Glasgow Coma Scale (GCS) and National Institutes of Health Stroke Scale (NIHSS) in predicting severity and treatment outcomes in patients with acute neuropathologies. Ninety patients were examined, including those with traumatic brain lesions (16.6%, n = 15), hemorrhagic stroke (52.2%, n = 47), and ischemic stroke (31.1%, n = 28). Patients were classified into two groups according to the outcome of the disease: those who survived (group I, 57.8%, n = 52) and those who died (group II, 42.2%, n = 38). In comparison with the survivors, the group of patients who died demonstrated an initial increase in neuron-specific enolase (NSE) by 1.23 and S100 by 6.45 times, and in dynamics by 1.5 and 7.4 times. A significant correlation with NIHSS and GCS was determined for NSE (r = 0.1149; P = 0.3073 and r = -0.0758; P = 0.5011) and for S100 (r = 0.3243; P = 0.0031 and r = -0.2661; P = 0.0163). The receiver operating characteristic (ROC) curves were 0.828 for S100 and 0.712 for NSE. The degree of sensitivity and specificity of the markers was studied. Increased levels of S100 and NSE correlated with NIHSS and GCS, with sensitivity of 80.77 and 63.46% and specificity of 42.11 and 73.68%, respectively, and were predictive of adverse disease outcome. The survival analysis showed that early detection of these biomarkers enables the timely prognostication of the progression of secondary brain injury and aids in implementing treatment.

Objective : To evaluate the effects of isolated impaired fasting glucose (IIFG) on brain injury in patients undergoing cardiopulmonary bypass (CPB) surgery. Methods : Patients with rheumatic heart valve disease who underwent elective mitral valve replacement were included and divided into control and IIFG groups. Pre-, intra-, and postoperative blood glucose levels, serum insulin levels, insulin resistance index (HOMA-IR), lactic acid levels, and neuron-specific enolase (NSE) and S100B levels were measured. The cerebral oxygen extraction ratio (OER) was calculated. Cognitive function was assessed via the Mini-Mental State Examination (MMSE). Results : HOMA-IR levels were higher in the IIFG group than the control group 30 min after the beginning of CPB, at the termination of CPB, and 2 h after the termination of CPB. Cerebral OER and lactic acid increased intraoperatively in both groups, especially in the IIFG group. NSE and S100B levels were higher in the IIFG group than in the control group at the termination of CPB, 2 h after the termination of CPB, and at 24 h postoperatively. The MMSE scores did not significantly differ between the two groups. Delirium occurred in two patients in the IIFG group, and one in the control group. No other signs and symptoms of brain injuries were detected in either group. Conclusions : The increased postoperative NSE and S100B levels in the IIFG group compared with controls may be associated with severe insulin resistance and stress hyperglycemia. However, the IIFG group did not have clinical manifestations of brain injuries, including cognitive impairment.

The aim of the given study was to test the in situ stability of biochemical markers of cerebral damage and acute phase response in the early post-mortem interval to assess their usability for forensic pathology. A monocentric, prospective study investigated post-mortem femoral venous blood samples at four time points obtained within 48 h post-mortem starting at the death of 20 deceased, using commercial immunoassays for the ten parameters: S100 calcium-binding protein B (S100B), glial fibrillary acidic protein (GFAP), neuron-specific enolase (NSE), brain-derived neurotrophic factor (BDNF), interleukin-6 (IL-6), C-reactive protein (CRP), procalcitonin (PCT), ferritin, soluble tumor necrosis factor receptor type 1 (sTNFR1), and lactate dehydrogenase (LDH). Significant changes in serum levels were observed only later than 2 h after death for all markers. Inter-laboratory comparability was high, and intra-assay precision was sufficient for most markers. Most of the biomarker levels depended on the severity of hemolysis and lipemia but were robust against freeze-thaw cycles. Serum levels increased with longer post-mortem intervals for S100B, NSE, ferritin, sTNFR1, and LDH (for all p < 0.001) but decreased over this period for CRP (p = 0.089) and PCT (p < 0.001). Largely unchanged median values were found for GFAP (p = 0.139), BDNF (p = 0.106), and IL-6 (p = 0.094). Serum levels of CRP (p = 0.059) and LDH (p = 0.109) did not differ significantly between the final ante-mortem (resuscitation) and the first post-mortem sample (moment of death). Collecting the post-mortem blood sample as soon as possible will reduce the influence of post-mortem blood changes. Serum GFAP for detection of cerebral damage as well as serum IL-6 and CRP as proof of acute phase response seemed to be preferable due to their in situ stability in the first 2 days after death.

Objective This study was performed to investigate the correlation among decreased regional cerebral oxygen saturation (rSO 2 ), blood levels of brain injury biomarkers, and postoperative cognitive disorder (POCD) after cardiac surgery with cardiopulmonary bypass (CPB). Methods This prospective observational study included 59 patients undergoing coronary artery bypass graft surgery with CPB. All patients underwent neuropsychological tests (Mini Mental State Evaluation, Rey Auditory Verbal Learning Test, digit span test, digit symbol substitution test, and Schulte table) the day before and 10 days after the surgery. The blood levels of two brain injury biomarkers, neuron-specific enolase (NSE) and glial fibrillary acidic protein (GFAP), were measured before and 1 day after the surgery. Results The rSO 2 decreased during surgery in 21 (35%) patients. POCD was detected in 22 (37%) patients. After the surgery, no significant changes in the GFAP blood level occurred in any patients. No significant correlations were found among the decreased rSO 2 , increased NSE blood level, and rate of POCD. Conclusion These results suggest that a decrease in rSO 2 during cardiac surgery is not necessarily related to the development of POCD or an increased blood level of the brain injury biomarker NSE.

Background: To investigate serum levels of brain injury markers in diabetic ketoacidosis (DKA) and the relation of these markers with clinical and radiological findings of brain injury and laboratory results., Methods: Twenty-nine patients with DKA, 30 with type 1 diabetes mellitus (T1DM), and 35 healthy children were included. Clinical and laboratory findings, and the Glasgow Coma Scale (GCS) were recorded. In the DKA group, neuron-specific enolase (NSE), S100 calcium-binding protein B (S100B) and glial fibrillary acidic protein (GFAP) levels were measured at baseline and 6 and 12 hours after treatment. Magnetic resonance imaging was performed in the DKA group to demonstrate any brain injury., Results: No clinical or radiological findings of brain injury were found in any of the patients with DKA. In the DKA group, S100B was significantly higher than the healthy control and T1DM groups, while GFAP and NSE levels were not different from controls and T1DM patients. No significant differences were found in GFAP, NSE and S100B levels according to severity of DKA, diabetes duration and GCS., Conclusion: NSE and GFAP levels do not increase in DKA patients without overt brain injury. Elevated levels of S100B, which is also synthesized from non-neuronal tissues, might arise from peripheral sources. A lack of concurrent increase in serum levels of these brain injury markers might result from the yet intact blood brain barrier or a true absence of neuronal damage. In order to reveal subclinical brain injury related to DKA, there is a need for studies concurrently assessing neurocognitive functions., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Unexpected neurological morbidity in Pediatric Intensive Care Units (PICUs) remains high and is difficult to detect proactively. Brain-specific biomarkers represent a novel approach for early detection of neurological injury. We sought to determine whether serum concentrations of neuron-specific enolase (NSE), myelin basic protein (MBP), and S100B, specific for neurons, oligodendrocytes, and glia, respectively, were predictive of neurological morbidity in critically ill children., Methods: Serum was prospectively collected on days 1-7 from diagnostically diverse PICU patients (n = 103). Unfavorable neurological outcome at hospital discharge was defined as Pediatric Cerebral Performance Category (PCPC) score of 3-6 with a deterioration from baseline. NSE, MBP, and S100B concentrations were measured by enzyme-linked immunosorbent assay., Results: Peak biomarker levels were greater in patients with unfavorable versus favorable neurological outcome [NSE 39.4 ± 44.1 vs. 12.2 ± 22.9 ng/ml (P = 0.005), MBP 9.1 ± 11.5 vs. 0.6 ± 1.3 ng/ml (P = 0.003), S100B 130 ± 232 vs. 34 ± 70 pg/ml (P = 0.04), respectively; mean ± SD]. Peak levels were each independently associated with unfavorable neurological outcome when controlling for presence of primary neurologic admission diagnosis and poor baseline PCPC using logistic regression analysis (NSE, P = 0.04; MBP, P = 0.004; S100B, P = 0.04), and had the following receiver operating characteristics: NSE 0.75 (0.58, 0.92), MBP 0.81 (0.66, 0.94), and S100B 0.80 (0.67, 0.93) (area under the curve [95% confidence intervals])., Conclusions: Prospectively collected brain-specific serum biomarkers predict unfavorable neurological outcome in critically ill children. Serum biomarkers used in conjunction with clinical data could be used to generate models predicting early detection of neurological injury, allowing for more timely diagnostic and therapeutic interventions, potentially reducing neurological morbidity in the PICU.

Aim: To investigate if the serum biomarkers of cerebral injury, neuron-specific enolase and S100b protein, may classify unfavourable neurological outcome after paediatric cardiac arrest., Methods: We performed a retrospective study of neuron-specific enolase and S100b measurements from 95 children treated in our paediatric cardiac intensive care unit after cardiac arrest. Neurological outcome at discharge was evaluated using the paediatric cerebral performance category scale, with unfavourable outcome defined as a change of >1 compared to pre-arrest status or death., Results: Fifty-eight patients (61.1%) survived to discharge with 48 (50.5%) having a favourable neurological outcome. We observed significantly higher levels of both biomarkers in the unfavourable outcome group at designated time points (neuron-specific enolase at 24, 48, and 72h and S100b at 12, 24, and 48h after cardiac arrest, p<0.05). Receiver operating characteristic areas under the curve for neuron-specific enolase were 0.83, 0.80, and 0.73 at time points 24, 48, and 72h and 0.87, 0.81, and 0.82 for S100b at 12, 24, and 48h after cardiac arrest, respectively. Neuron-specific enolase measurement at 24h after cardiac arrest was an independent predictor of unfavourable outcome in a multivariable analysis., Conclusions: Neuron-specific enolase and S100b classify unfavourable neurological outcome in this large paediatric cardiac arrest cohort. Further multi-institutional prospective studies to comprehensively evaluate the diagnostic accuracy of these biomarkers under various clinical conditions and to determine reliable cut-off values in children are warranted., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objective: This study investigates the clinical value of monitoring blood levels of tumor necrosis factor-α (TNF-α), high mobility group protein Bl (HMGBl), and neuron-specific enolase (NSE), and examining an amplitude-integrated electroencephalogram (aEEG) for the diagnosis and short-term prognosis of brain damage caused by neonatal asphyxia., Patients and Methods: Sixty full-term neonates born in Yidu Central Hospital from January to December 2015 were enrolled in the study. The neonates were classified into one of 3 groups: 23 neonates in the mild asphyxia group, 7 in a severe asphyxia group and 30 in a control group admitted to the NICU but without asphyxia. The neonates presenting asphyxia received standard neonatal resuscitation before they were transferred to the NICU. The dynamic changes of the umbilical artery/peripheral blood TNF-α, HMGBl, and NSE levels and aEEG results were monitored and compared among the groups., Results: The umbilical artery and serum TNF-α, HMGBl, and NSE levels at day 1 were significantly higher in the two asphyxia groups than in the control group; and the values were higher in the severe asphyxia group (p <0.05). Furthermore, the correlation coefficients between TNF-α and HMGB1, TNF-α and NSE, and HMGB1 and NSE at all the monitoring time points were positive: 0.5516, 26.943 and 15.87, respectively (p <0.001). Additionally, the neonates with abnormal aEEG results at 6 hours postpartum had higher serum TNF-α, HMGBl and NSE levels than those with normal aEEG results (p <0.05). The patients with persistently abnormal or progressively deteriorating aEEG results usually had a poor evolution., Conclusions: The dynamic monitoring of TNF-α, HMGBl, and NSE levels combined with aEEG can provide useful evidence for the early diagnosis, the determination of severity and the short-term prognosis of brain damage caused by neonatal asphyxia.

The object of this work was to explore if blood based biomarkers of brain damage could predict subclinical brain lesions and clinical outcome during follow-up in asymptomatic hypertensive patients. This was a cross-sectional study including 101 patients with essential hypertension and no clinical evidence of neurological disease and 53 healthy controls, followed by a longitudinal study of 62 hypertensive patients for an average of 33 months. Serum concentrations of two brain specific proteins (S100B and neuron specific enolase - NSE) were determined at inclusion. Fundoscopic exploration, brain MRI and echocardiographic studies were also performed. Clinical outcome at follow-up was registered: transient ischemic attack (TIA), stroke, vascular headache or migraine, cardiovascular events and death. Higher serum NSE and S100B concentrations were observed in hypertensive patients; and multiple regression analysis revealed independent associations of clinical variables and more severe white matter lesions only with NSE concentration. A panel combining two clinical variables (blood pressure>140/90 and years of hypertension>10) and serum NSE>13 μg/L predicted more severe white matter lesions with 80% sensitivity and 94.4% specificity. Higher NSE levels at inclusion were associated not only with the occurrence of vascular events related with the CNS (stroke, TIA and vascular headache), but also with an earlier presentation of these events during the follow-up period. Serum NSE concentration could be a useful biomarker to predict subclinical brain damage and future vascular events related with the CNS in hypertension. Blood based biomarkers could aid in filtering hypertensive patients with a higher risk of cerebrovascular disease for brain MRI scanning., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: Despite several experimental studies on the role of S100B and NSE in fractures, no studies on the influence of surgery on the biomarker serum levels have been performed yet., Methods: The serum levels of S100B and NSE were analysed in patients with fractures that were located in the spine (group 1, n = 35) or in the lower extremity (group 2, n = 32) pre- and post-operatively., Results: The mean S100B serum level showed a significant increase (p = 0.04) post-surgery in the patients of group 1. In patients undergoing acute surgery (< 24 hours) the mean S100B serum level was 0.23 ± 0.22 μg L(-1) pre-operatively and 1.24 ± 1.38 μg L(-1) post-operatively. Likewise, the mean S100B serum level significantly increased in group 2 after surgery (p < 0.0001). In this group patients undergoing acute surgery showed a mean S100B serum level of 0.23 ± 0.14 μg L(-1) and 1.11 ± 0.73 μg L(-1) pre- and post-operatively., Conclusion: This study demonstrates significant alterations of the biomarker S100B serum levels in patients undergoing surgery. Higher S100B serum levels were found within 24 hours and might be related to the acute fracture. The NSE serum levels were unchanged and this biomarker may offer the probability to serve as a future outcome predictor in studies with patients with traumatic brain injury and additional extracerebral injuries.

Background: Cerebral neurochemicals are markers of traumatic brain injury (TBI)., Objectives: 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)., Methods: 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., Results: 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)., Conclusions: 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., (© The Author(s) 2015.)

Traumatic brain injury (TBI) is a common cause of death and disability, worldwide. Early determination of injury severity is essential to improve care. Neurofilament light (NF-L) has been introduced as a marker of neuroaxonal injury in neuroinflammatory/-degenerative diseases. In this study we determined the predictive power of serum (s-) and cerebrospinal fluid (CSF-) NF-L levels towards outcome, and explored their potential correlation to diffuse axonal injury (DAI). A total of 182 patients suffering from TBI admitted to the neurointensive care unit at a level 1 trauma center were included. S-NF-L levels were acquired, together with S100B and neuron-specific enolase (NSE). CSF-NF-L was measured in a subcohort (n = 84) with ventriculostomies. Clinical and neuro-radiological parameters, including computerized tomography (CT) and magnetic resonance imaging, were included in the analyses. Outcome was assessed 6 to 12 months after injury using the Glasgow Outcome Score (1-5). In univariate proportional odds analyses mean s-NF-L, -S100B and -NSE levels presented a pseudo-R2 Nagelkerke of 0.062, 0.214 and 0.074 in correlation to outcome, respectively. In a multivariate analysis, in addition to a model including core parameters (pseudo-R2 0.33 towards outcome; Age, Glasgow Coma Scale, pupil response, Stockholm CT score, abbreviated injury severity score, S100B), S-NF-L yielded an extra 0.023 pseudo-R2 and a significantly better model (p = 0.006) No correlation between DAI or CT assessed-intracranial damage and NF-L was found. Our study thus demonstrates that S-NF-L correlates to TBI outcome, even if used in models with S100B, indicating an independent contribution to the prediction, perhaps by reflecting different pathophysiological processes, not possible to monitor using conventional neuroradiology. Although we did not find a predictive value of NF-L for DAI, this cannot be completely excluded. We suggest further studies, with volume quantification of axonal injury, and a prolonged sampling time, in order to better determine the connection between NF-L and DAI.

Background: Several studies have demonstrated that magnesium (Mg) plays an important role in the prevention and treatment of central nervous system (CNS) insults. In this study, we tested the effect of intravenous magnesium sulfate (MgSO4) on the outcome of patients with brain tumors who underwent craniotomy. The outcome was defined clinically as the Barthel index score and paraclinically as blood levels of NSE (neuron-specific enloase) and S100Β protein., Methods: Sixty patients were randomly divided into two groups of 30 patients: the treatment and control groups. In the treatment group, 5 g of MgSO4 in normal saline was infused in 6 h 2 days before surgery, and the same dosage was repeated the day before and during surgery. The control group received placebo. Serum S100Β and NSE concentrations were measured at baseline before administration of magnesium, before surgery, and on the 2nd postoperative day. The Barthel index score was evaluated and registered before surgery, 3, and 6 months after the operation., Results: The study results showed a significant change in S100Β protein levels before and after surgery (p < 0.05), but we could not find similar results for NSE protein and the Barthel index score. There was a correlation between NSE protein and the Barthel index., Conclusions: The results of this study revealed that administration of intravenous MgSO4 before and during surgery is safe and effective in reducing S100B protein levels in patients undergoing supratentorial craniotomy for brain tumors. Further studies to elucidate the pathophysiology of brain injuries and role of magnesium are warranted.

Objective: to study the content of biomarkers of diagnostic and prognostic value in the assessment of traumatic brain injury (TBI) severity in children., Material and Methods: Authors determined the levels of glial protein S100B, neuronspecific enolase (NSE), autoantibodies (aAb) to glutamate receptors and natural autoantibodies (nAb) to S100B and brain-derived neurotrophic factor (BDNF) in serum/plasma of children with different outcomes of TBI. All parameters were analyzed in the 1-3rd, 7-8th, 14-15th and 20-23rd days after TBI, and, in some cases of severe brain injury and long stay patients in hospital, in 11-12 months after TBI. The severity and outcome of TBI were assessed according the Glasgow coma scale (GCS) and the Glasgow outcome scale (GOS), respectively., Results and Conclusion: The content of NSE and S100B increased immediately after TBI regardless of TBI severity, but in cases with favorable outcome it dropped to a normal level in the first 3 days. The maximum levels of S100B protein and NSE were observed in children with fatal TBI, and higher values were observed throughout the post-traumatic period. The low levels of aAb to NR2-subtype of glutamate receptors that were similar to controls and the high level of nAb to S100B in the first days after severe TBI indicate the failure of compensatory-adaptive immunological mechanisms and the high permeability of the brain-blood barrier, which were poor prognostic signs for children with severe TBI. Mild and severe TBI with full recovery were accompanied by higher values of ВDNF in the 1st day followed by a decline to the 3rd day. The level of BDNF in the 1st day of TBI was the lowest and subsequently continued to decline in patients with severe TBI with fatal outcome.

Objective: The association was studied of intracranial pressure (ICP) and cerebral perfusion pressure (CPP) on S-100B and neuron-specific enolase (NSE) in severe traumatic brain injury (sTBI). The relationship was explored between biomarkers, ICP, CPP, CT-scan classifications and the clinical outcome., Materials and Methods: Data were collected prospectively and consecutively in 48 patients with Glasgow Coma Scale score ≤ 8, age 15-70 years. NSE and S-100B were analysed during 5 consecutive days. The initial and follow-up CT-scans were classified according to the Marshall, Rotterdam and Morris-Marshall classifications. Outcome was evaluated with extended Glasgow outcome scale at 3 months., Results: Maximal ICP and minimal CPP correlated with S-100B and NSE levels. Complex relations between biomarkers and CT classifications were observed. S-100B bulk release (AUC = 0.8333, p = 0.0009), and NSE at 72 hours (AUC = 0.8476, p = 0.0045) had the highest prediction power of mortality. Combining Morris-Marshall score and S-100B bulk release improved the prediction of clinical outcome (AUC = 0.8929, p = 0.0008)., Conclusion: Biomarker levels are associated with ICP and CPP and reflect different aspects of brain injury as evaluated by CT-scan. The biomarkers might predict mortality. There are several pitfalls influencing the interpretation of biomarker data in respect to ICP, CPP, CT-findings and clinical outcome.

Objective: To study blast-induced traumatic brain injury (bTBI) characteristics in confined space., Methods: The goats were placed at the column-like buildings with trinitrotoluene (TNT) as the source of the blast wave. The pressure was recorded at 2-8 m from the explosion center. The systemic physiology, electroencephalogram (EEG), serum level of S-100beta, and neuron specific enolase (NSE) were determined pre and post the exposure. Neuroanatomy and neuropathology were observed 4 hours after the exposure., Results: The blast waveform was composed of two peaks from the incident and reflection wave with a range of pressure-duration from 555/913 kPa-0.663 milliseconds at 2 m to 45/71 kPa-2.7/2.367 milliseconds at 8 m. At 2 m, the goats experienced brain depression while the heart rate and respiratory rate concomitantly increased with bloody foam fluid emission from the nose and the mouth. Of the goats, 88.89% were burned. The distinctive gross neuroanatomical changes were congestive expansion of surface vessels on the hemisphere cerebellum and brainstem along with subarachnoid hemorrhage on the frontal lobe, mesencephalon, and brainstem. Subarachnoid hemorrhage, enlarged perivascular space, vascular dilatation and congestion, and parenchymal hemorrhagic could be easily observed microscopically. High amplitude and low frequency of waveforms appeared in the EEG. The serum concentration of S-100beta and NSE were elevated. Although these pathophysiological changes diminished with increasing distance from the explosive center, these changes existed for the 8 m subjects., Conclusions: Blast-induced traumatic brain injury can be induced by a complex blast wave with a pressure and duration of 45/71 kPa and 2.7/2.367 milliseconds. Its severity is related to the features and waveforms of the blast.

The main purpose of this study was to assess the role of S100B protein, neuron-specific enolase (NSE), and glial fibrillary acidic protein (GFAP) in the evaluation of hypoxic brain injury in acute carbon monoxide (CO)-poisoned patients. This cross-sectional study was conducted among the patients with acute CO poisoning who referred to the emergency department in a 1-year period. Serum levels of S100B protein, NSE, and GFAP were determined on admission. A total of 55 CO-poisoned patients (mean age ± standard deviation, 45 ± 20.3 years; 60% women) were included in the study. The control group consisted of 25 healthy adults. The patients were divided into two groups according to whether they were conscious or unconscious. The serum levels of S100B, NSE, and GFAP were higher in patients than that in the control group. There was no significant difference between unconscious and conscious patients with respect to these markers. There was a statistically significant difference between the conscious and unconscious patients and the control group in terms of S100B and NSE levels. There was also a statistically significant difference between the unconscious patients and the control group in terms of GFAP levels. Increased serum S100B, NSE, and GFAP levels are associated with acute CO poisoning. These biomarkers can be useful in assessing the clinical status of patients with CO poisoning., (© The Author(s) 2014.)

Traumatic brain injury (TBI) is a frequent and clinically highly heterogeneous neurological disorder with large socioeconomic consequences. NeuroAid (MLC601 and MLC901), a Traditional Medicine used in China for patients after stroke has been previously reported to induce neuroprotection and neuroplasticity. This study was designed to evaluate the neuroprotective and neuroregenerative effects of MLC901 in a rat model of TBI. TBI was induced by a moderate lateral fluid percussion applied to the right parietal cortex. MLC901 was injected intraperitoneally at 2h post-TBI, and then administered in drinking water at a concentration of 10mg/ml until sacrifice of the animals. The cognitive deficits induced by TBI were followed by using the "what-where-when" task, which allows the measurement of episodic-like memory. MLC901 treatment decreased brain lesions induced by TBI. It prevented the serum increase of S-100 beta (S100B) and neuron-specific enolase (NSE), which may be markers to predict the neurologic outcome in human patients with TBI. MLC901 reduced the infarct volume when injected up to 2h post-TBI, prevented edema formation and assisted its resolution, probably via the regulation of aquaporin 4. These positive MLC901 effects were associated with an upregulation of vascular endothelial growth factor (VEGF) as well as an increase of endogenous hippocampal neurogenesis and gliogenesis around the lesion. Furthermore, MLC901 reduced cognitive deficits induced by TBI. Rats subjected to TBI displayed a suppression of temporal order memory, which was restored by MLC901. This work provides evidence that MLC901 has neuroprotective and neurorestorative actions, which lead to an improvement in the recovery of cognitive functions in a model of traumatic brain injury., (Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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., Methods: PubMed and Embase were searched for relevant studies published up to October 2013. Full-text publications on the relationship of NSE to TBI were included if the studies concerned patients with closed head injury, NSE levels in serum after injury, and Glasgow Outcome Scale (GOS) or Extended GOS (GOSE) scores or mortality. Study design, inclusion criteria, assay, blood sample collection time, NSE cutoff, sensitivity and specificity of NSE for mortality prediction (if sufficient information was provided to calculate these values), and main outcomes were recorded., Results: Sixteen studies were eligible for the current meta-analysis. In the six studies comparing NSE concentrations between TBI patients who died and those who survived, NSE concentrations correlated with mortality (M.D. 0.28, 95% confidence interval (CI), 0.21 to 0.34; I2 55%). In the eight studies evaluating GOS or GOSE, patients with unfavorable outcomes had significantly higher NSE concentrations than those with favorable outcomes (M.D. 0.24, 95% CI, 0.17 to 0.31; I2 64%). From the studies providing sufficient data, the pooled sensitivity and specificity for mortality were 0.79 and 0.50, and 0.72 and 0.66 for unfavorable neurological prognosis, respectively. The areas under the SROC curve (AUC) of NSE concentrations were 0.73 (95% CI, 0.66-0.80) for unfavorable outcome and 0.76 (95% CI, 0.62-0.90) for mortality., Conclusions: Mortality and unfavorable outcome were significantly associated with greater NSE concentrations. In addition, NSE has moderate discriminatory ability to predict mortality and neurological outcome in TBI patients. The optimal discrimination cutoff values and optimal sampling time remain uncertain because of significant variations between studies.

Objective: To determine whether a model of transient mass-type brain damage (MTBD) in the rat produces early release of neurospecific enolase (NSE) and protein S100B in peripheral blood, as an expression of the induced brain injury., Design: An experimental study with a control group., Setting: Experimental operating room of the Institute of Biomedicine (IBiS) of Virgen del Rocío University Hospital (Seville, Spain)., Participants: Fourteen adult Wistar rats., Interventions: Blood was sampled at baseline, followed by: MTBD group, a trephine perforation was used to insert and inflate the balloon of a catheter at a rate of 500 μl/20 sec, followed by 4 blood extractions every 20 min. Control group, the same procedure as before was carried out, though without trephine perforation., Primary Study Variables: Weight, early mortality, serum NSE and S100B concentration., Results: Differences in NSE and S100B concentration were observed over time within the MTBD group (P<.001), though not so in the control group. With the exception of the baseline determination, differences were observed between the two groups in terms of the mean NSE and S100B values. Following MTBD, NSE and S100B progressively increased at all measurement timepoints, with r=0.765; P=.001 and r=0.628; P=.001, respectively. In contrast, the control group showed no such correlation for either biomarker., Conclusions: Serum NSE and S100B concentrations offer an early indication of brain injury affecting the gray and white matter in an experimental model of mass-type MTBD in the rat., (Copyright © 2013 Elsevier España, S.L. and SEMICYUC. All rights reserved.)

There is a lack of reliable serum biomarkers for routine use in the diagnostic workup of people with traumatic brain injury. Multiple biomediators and biomarkers have been described in the pertinent literature in recent years; however, only a few candidate molecules have been associated with high sensitivity and high specificity for risk stratification and outcome prediction after traumatic brain injury. This review was designed to provide an overview of the state of the art regarding established serum biomarkers in the field and to outline future directions of investigation.

Objectives: Morbidity and mortality in children with cardiac arrest largely result from neurologic injury. Serum biomarkers of brain injury can potentially measure injury to neurons (neuron-specific enolase), astrocytes (S100b), and axons (myelin basic protein). We hypothesized that serum biomarkers can be used to classify outcome from pediatric cardiac arrest., Design: Prospective observational study., Setting: Single tertiary pediatric hospital., Patients: Forty-three children with cardiac arrest., Interventions: None., Measurements and Main Results: We measured serum neuron-specific enolase, S100b, and myelin basic protein on days 1-4 and 7 after cardiac arrest. We recorded demographics, details of the cardiac arrest and resuscitation, and Pediatric Cerebral Performance Category at hospital discharge and 6 months. We analyzed the association of biomarker levels at 24, 48, and 72 hours with favorable (Pediatric Cerebral Performance Category 1-3) or unfavorable (Pediatric Cerebral Performance Category 4-6) outcome and mortality. Forty-three children (49% female; mean age of 5.9 ± 6.3) were enrolled and 17 (40%) died. Serum S100b concentrations peaked earliest, followed by neuron-specific enolase and finally myelin basic protein. Serum neuron-specific enolase and S100b concentrations were increased in the unfavorable versus favorable outcome group and in subjects who died at all time points (all p < 0.05). Serum myelin basic protein at 24 and 72 hours correctly classified survival but not good versus poor outcome. Using best specificity, serum S100b and neuron-specific enolase had optimal positive and negative predictive values at 24 hours to classify both favorable versus unfavorable outcome and survival, whereas serum myelin basic protein's best accuracy occurred at 48 hours. Receiver operator curves for serum S100b and neuron-specific enolase to classify favorable versus unfavorable outcome at 6 months were superior to clinical variables., Conclusions: Preliminary data show that serum S100b, neuron-specific enolase, and myelin basic protein may aid in outcome classification of children surviving cardiac arrest.

Objectives: Extracorporeal life support (ECLS) is a rescue option in critically ill patients. Since fast available and appropriate for respiratory and circulatory failure, it is frequently applied in resuscitation scenarios. Neurological injury is a complication common in ECLS patients limiting outcome, particularly after resuscitation. In this study, the institutional ECLS database was used to correlate neuron-specific enolase (NSE) serum peak values with outcome of patients supported with venoarterial (VA) ECLS during cardiopulmonary resuscitation (CPR)., Methods: From January 2011 to August 2012, 31 patients were provided with a VA ECLS during CPR (external cardiac massage). Serum NSE peaks were monitored and correlated with neurological outcome and hospital mortality. Patients were divided into two groups with mild-to-moderate and high NSE levels (cut-off value 100 μg/l)., Results: High NSE levels were seen in 7 patients (mean 218 ± 155 μg/l) and mild-to-moderate levels in 24 patients (50 ± 23 μg/l, P = 0.0001). Duration of extracoporeal support was comparable in both groups (6.3 ± 7.5 vs 5.0 ± 4.5 days, P = n.s.). Patients with mild-to-moderate NSE levels were significantly older than those with high NSE levels (58 ± 16 vs 44 ± 15 years, P = 0.02). Six patients with high NSE levels (86%) developed severe neurological complications. Though 4 patients could be weaned from extracorporeal support, hospital mortality was 86% (6 patients). In contrast, patients with mild-to-moderate NSE levels had a hospital mortality of 46% (11 patients). Eighteen patients (75%) could be weaned from the device, and incidence of major neurological events was 29% (6 patients) only. Serum pH and lactate levels before ECLS implantation were significantly lower in patients with mild-to-moderate NSE values (pH: 7.23 ± 0.04 vs 6.93 ± 0.12, P = 0.039; lactate: 106 ± 11 vs 161 ± 16 mg/l, P = 0.023)., Conclusions: High NSE serum levels after ECLS correspond to poor neurological outcome and considerable mortality. Therefore, early neuroimaging is reasonable for determining therapeutic strategies in patients with high NSE peaks after resuscitation and extracorporeal support.

Traumatic brain injury (TBI) is a leading cause of mortality and disability. Acute postinjury insults after TBI, such as hypoxia, contribute to secondary brain injury and worse clinical outcomes. The functional and neuroinflammatory effects of brief episodes of hypoxia experienced following TBI have not been evaluated. Our previous studies have identified interleukin 6 (IL-6) as a potential mediator of mild TBI-induced pathology. In the present study, we sought to determine the effects of brief hypoxia on mild TBI and whether IL-6 played a role in the neuroinflammatory and functional deficits after injury. A murine model of mild TBI was induced by a weight drop (500 g from 1.5 cm). After injury, mice were exposed to immediate hypoxia (FIO2 = 15.1%) or normoxia (FIO2 = 21%) for 30 min. Serum and brain samples were analyzed for inflammatory cytokines 24 h after TBI. Neuron-specific enolase was measured as a serum biomarker of brain injury. Evaluation of motor coordination was performed for 5 days after TBI using a rotarod device. In some animals, anti-IL-6 was administered following TBI and hypoxia to neutralize systemic IL-6. Mice undergoing TBI had significant increases in brain injury. Exposure to brief hypoxia after TBI resulted in a more than 5-fold increase in serum neuron-specific enolase. This increase was associated with increases in serum and brain cytokine expression, suggesting that brief hypoxia exacerbates systemic and brain inflammation. Neutralization of IL-6 suppressed postinjury neuroinflammation and neuronal injury. In addition, TBI and hypoxia induced significant motor coordination deficits that were completely abrogated by IL-6 blockade. Exposure to hypoxia after TBI induces neuroinflammation and brain injury. These changes can be mitigated by neutralization of systemic IL-6. Interleukin 6 blockade also corrected the TBI-induced deficit in motor coordination. These data suggest that systemic IL-6 modulates the degree of neuroinflammation and contributes to reduced motor coordination after mild TBI.

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.

Background: Mild traumatic brain injury (TBI) is a serious public health concern affecting more than 1.7 million people in the United States annually. Mild TBI is difficult to diagnose and is clinically associated with impaired motor coordination and cognition., Methods: We subjected mice to a mild TBI (mTBI-1 or mTBI-2) induced by a weight drop model. We assessed brain injury histologically and biochemically, the latter by serum neuron-specific enolase and glial fibrillary acidic protein. Systemic and brain inflammation were measured by cytokine array. We determined blood-brain barrier integrity by cerebral vascular leakage of micromolecular and macromolecular fluorescent molecules. We evaluated mice using a rotarod device and novel object recognition to measure motor coordination and cognition, respectively., Results: Mice undergoing mTBI-1 or mTBI-2 had significant deficits in motor coordination and cognition for several days after injury compared with controls. Furthermore, both mTBI-1 and mTBI-2 caused micromolecular leakage in the blood-brain barrier, whereas only mTBI-2 caused macromolecular leakage. Serum neuron-specific enolase and glial fibrillary acidic protein were elevated acutely and corresponded to the degree of injury, but returned to baseline within 24 h. Serum cytokines interleukin-6 and keratinocyte-derived chemokine were significantly increased within 90 min of TBI. Interleukin-6 levels correlated with the degree of injury., Conclusions: The current study provides a reproducible model of mild TBI in mice that exhibits pathologic features of mild TBI in humans. Furthermore, our data suggest that serum cytokines, such as IL-6, may be effective biomarkers for severity of head injury., (Copyright © 2013 Elsevier Inc. All rights reserved.)

This study investigated the effect of penehyclidine hydrochloride (PHC) on regulatory mediators during the neuroinflammatory response and cerebral cell apoptosis following cardiopulmonary bypass (CPB). Forty-eight rats were randomly divided among 4 groups as follows: sham-operation, vehicle, low-dose PHC (0.6 mg·(kg body mass)(-1)), and high-dose PHC (2.0 mg·(kg body mass)(-1)). CPB was performed in the latter 3 groups. The plasma levels of neuron specific enolase (NSE) and S-100B were tested with ELISA. Real-time PCR and Western blotting were used to evaluate the expression levels of matrix metalloproteinase-9 (MMP-9), IL-10, caspase-3, Bcl-2, and p38 in brain tissue. The ultrastructure of hippocampus tissue was examined under an electron microscope. PHC attenuated the increase of plasma NSE and S-100B following CPB. MMP-9, cleaved caspase-3, and phosphorylated p38 expression were substantially increased in the vehicle group compared with the sham-operation group and gradually diminished with increasing doses of PHC. IL-10 and Bcl-2 expression were markedly lower in the vehicle group than in the sham-operation group and gradually recovered with increasing doses of PHC. PHC attenuated the histopathological changes of cerebral injury following CPB. PHC favorably regulates the inflammatory response and reduces markers of neuronal injury following CPB, potentially by reducing p38 and caspase-3 activation.

Objective: To evaluate the relationship between brain damage biomarkers and mortality in the intensive care unit (ICU)., Methods: The sample comprised 70 patients admitted to an ICU. Blood samples were collected from all patients on ICU admission, and levels of S100β and neuron-specific enolase (NSE) were determined by ELISA., Results: Acute Physiologic and Chronic Health Evaluation (APACHE II) score was associated with mortality, but NSE and S100β were not associated with this outcome. In contrast, S100β levels were significantly higher in delirious and non-delirious patients who required mechanical ventilation during ICU stay., Conclusion: Levels of brain biomarkers at the time of ICU admission did not predict mortality in critically ill patients.

In recent years, the measurement of biomarkers following neurotrauma assisted in improving outcome prediction and guiding therapy. The use of neuroproteins as diagnostic parameters requires a detailed knowledge of their dynamics in biological fluids for an appropriate interpretation. S100B is the most widely studied neuromarker, and its concentration in serum and cerebrospinal fluid (CSF) reflects the extent of brain damage. Neuron-specific enolase (NSE) is considered reflecting neuronal damage, while Beta-Trace is a lepto-meningeal protein used to diagnose CSF leakage. In five patients treated with an external ventricular drain (EVD) because of aneurysmal subarachnoid hemorrhage (SAH, n=3) or postinfectious hydrocephalus (n=2), an EVD exchange was performed 8 to 12 days after initial insertion. S100B and NSE were measured with the Cobas e411(®) electrochemiluminescence assay (Roche Diagnostics, Mannheim, Germany) and Beta-Trace with the BN Pro Spec(®) nephelometer (Dade Behring/Siemens, Germany) 1 h before EVD exchange, upon the insertion of the new drain, and 1, 3, 6, 12, 18, 24 and 48 h after EVD exchange. Before EVD exchange, S100B CSF concentrations were within the normal range in all patients (1.48 ± 0.37 μg/L), while NSE CSF concentrations were normal in four of five patients (6.51 ± 2.98 μg/L). Following EVD exchange, S100B and NSE CSF levels peaked significantly at 3 h after insertion of the new drain (S100B 39.02 ± 9.17 μg/L; NSE 54.80 ± 43.34 μg/L). S100B serum levels were slightly increased 6 to 24 h after EVD exchange. Beta-Trace concentrations in the CSF were not altered by EVD insertion. Our data demonstrate that EVD insertion results in a distinct increase of S100B and NSE concentrations in the CSF. Thus, the tampering of brain-derived protein concentrations in the CSF by diagnostic or therapeutic procedures has to be considered in the interpretation of neuromarker levels.

Object: The role of the neuromarkers S100B protein and neuron-specific enolase (NSE) in minor head injury is well established. Moreover, there are sensitive decision rules available in the literature to identify clinically important brain lesions. However, it is not clear if using the biomarkers has an influence on the predictability of the decision rule. The purpose of this study was to determine if a set of preclinical and clinical parameters combined with 2 neuromarker levels could serve as reliable guidance for accurate diagnosis., Methods: Prospective evaluation of a cohort of head trauma patients with Glasgow Coma Scale scores of 13-15 was performed at an academic, Level I trauma center. Blood samples and cranial CT studies were obtained for all patients within 3 hours after injury. The hypothesis of the study was whether the combination of an increase of S100B and NSE levels in serum and other defined risk factors are associated with a pathological finding on CT. A forward stepwise logistic regression model was used., Results: The study included 107 head trauma patients with a mean age of 59 ± 23 years. Twenty-five patients (23.4%) had traumatic lesions on CT. Eight patients underwent craniotomy. The analysis provided a model with good overall accuracy for discriminating cases with clinically important brain injury, including the 6 variables of S100B, NSE, nausea, amnesia, vomiting, and loss of consciousness. The area under the curve (AUC) was 0.88 (0.83-0.93). The receiver operating characteristic curve plots detecting clinically important brain injury for the single variables of S100B and NSE showed an AUC of 0.63 and 0.64, respectively. Conclusions The integration of the neuromarker panel as part of a diagnostic rule including the high-risk factors of nausea, vomiting, amnesia, and loss of consciousness is safe and reliable in determining a diagnosis, pending the availability of more brain-specific neuromarkers. CLINICAL TRIAL REGISTRATION NO.: NCT00622778 (ClinicalTrials.gov).

Objective: To observe the differences in bispectral index (BIS) in unconscious patients with acute brain injury due to different pathogenic factors, and approach its clinical significance., Methods: A retrospective study was conducted. One hundred and twenty-two unconscious patients with acute brain injured admitted to the intensive care unit (ICU) from March 2009 to August 2012 were involved. According to the pathogenic factors, all patients were divided into direct injury group (n=66) and indirect injury group (n=56). Based on BIS value, all patients were divided into the BIS<60 group (n=80) and the BIS≥60 group (n=42). The BIS was continuously measured for 12 hours during the first 3 days, or 24 hours after stoppage of sedative after admission to ICU. The mean value of BIS (BISmean) was evaluated. The acute physiology and chronic health evaluationII (APACHEII) score, probability of survival (PS) and Glasgow coma score (GCS) were recorded. On the same day, the serum protein S100 and neuron-specific enolase (NSE) were determined. The mortality and the rate of the poor neurological outcome were analyzed., Results: (1) There were no significant differences in the age, sex, APACHEII score, PS and days of stay in ICU between the direct and indirect injury groups. (2) BISmean and GCS in direct injury group were significantly lower than those of the indirect injury group [BISmean: 39.0 (2.5, 58.0) vs. 59.0 (42.0, 71.0), GCS score: 3 (3, 5) vs. 4 (3, 6), both P<0.01], while serum S100 levels was significantly higher [2.30 (0.75, 6.66) mg/L vs. 0.84 (0.40, 3.62) mg/L, P<0.01]. There was no significant difference in the NSE level between the direct and indirect injury groups. (3) The mortality rate and poor neurological outcome rate in BIS<60 group were significantly higher than the BIS≥60 group (mortality rate: 67.50% vs. 40.48%, poor neurological outcome rate: 86.25% vs. 66.67%, P<0.01 and P<0.05). In the BIS<60 group, there were no significant differences in the mortality and poor neurological outcome rate between direct and indirect injury group., Conclusions: There are differences in pathogenic factors, the injury mechanism, and the degree of the brain injury between the direct and indirect injury groups. BIS monitoring could help judge the degree of different kinds of brain injury. BIS<60 indicates poor prognosis and neurological outcome in spite of the inducing factor of brain injury.

A peripheral indicator of the presence and magnitude of brain injury has been a sought-after tool by clinicians. We measured neuron-specific enolase (NSE), myelin basic protein (MBP), and S100B, prior to and after scaled cortical impact in immature pigs, to determine if these purported markers increase after injury, correlate with the resulting lesion volume, and if these relationships vary with maturation. Scaled cortical impact resulted in increased lesion volume with increasing age. Concentrations of NSE, but not S100B or MBP, increased after injury in all age groups. The high variability of S100B concentrations prior to injury may have precluded detection of an increase due to injury. Total serum markers were estimated, accounting for the allometric growth of blood volume, and resulted in a positive correlation of both NSE and S100B with lesion volume. Even with allometric scaling of blood volume and a uniform mechanism of injury, NSE had only a fair to poor predictive value. In a clinical setting, where the types of injuries are varied, more investigation is required to yield a panel of serum markers that can reliably predict the extent of injury. Allometric scaling may improve estimation of serum marker release in pediatric populations.

Objective: To explore the relationship between interleukin-6 (IL-6) production and central nervous injury in septic patients., Methods: Twenty-two septic patients without central nervous system diseases were examined for serum IL-6 and neuron-specific enolase (NSE) levels, and the serum NSE levels and APACHEII scores were compared between patients with low, moderate, and high serum IL-6 levels. The correlations between NSE, APACHEII and serum IL-6 were analyzed., Results: In patients with low, moderate, and high serum IL-6 levels, the serum levels of NSE were 10.29∓4.05, 16.06∓5.84 and 23.97∓3.28 µg/L, respectively, showing a significant difference between the 3 groups (P<0.001). The APACHEII scores also differed significantly between the 3 groups (14.17∓4.67, 16.40∓4.84, and 24.00∓6.26, respectively, P=0.009). Correlation analysis showed significant positive correlations of IL-6 with NSE (r=0.788, P<0.001) and with APACHEII scores (r=0.733, P<0.001)., Conclusion: In septic patients, serum IL-6 level is significantly correlated with the severity of sepsis and brain injury, and can be used as a marker to monitor brain injury in septic patients.

Objective: To determine if early serum S100B and neuron-specific enolase (NSE) levels are associated with neuroradiographic and clinical evidence of brain injury in newborns with encephalopathy., Study Design: Patients who received therapeutic whole-body hypothermia were prospectively enrolled in this observational study. Serum specimens were collected at 0, 12, 24, and 72 hours of cooling. S100B and NSE levels were measured by enzyme linked immunosorbent assay. Magnetic resonance imaging was performed in surviving infants at 7-10 days of life. Standardized neurologic examination was performed by a child neurologist at 14 days of life. Multiple linear regression analyses were performed to evaluate the association between S100B and NSE levels and unfavorable outcome (death or severe magnetic resonance imaging injury/significant neurologic deficit). Cutoff values were determined by receiver operating curve analysis., Results: Newborns with moderate to severe encephalopathy were enrolled (n = 75). Median pH at presentation was 6.9 (range, 6.5-7.35), and median Apgar scores of 1 at 1 minute, 3 at 5 minutes, and 5 at 10 minutes. NSE and S100B levels were higher in patients with unfavorable outcomes across all time points. These results remained statistically significant after controlling for covariables, including encephalopathy grade at presentation, Apgar score at 5 minutes of life, initial pH, and clinical seizures., Conclusion: Elevated serum S100B and NSE levels measured during hypothermia were associated with neuroradiographic and clinical evidence of brain injury in encephalopathic newborns. These brain-specific proteins may be useful immediate biomarkers of cerebral injury severity., (Copyright © 2012 Mosby, Inc. All rights reserved.)

The management of severe traumatic brain injury (TBI) focuses on prevention and treatment of secondary insults such as cerebral hypoxia (CH). There are a number of biomarkers that are thought to play a part in secondary injury following severe TBI. This study evaluates the association between S100β, neuron-specific enolase (NSE), and glial fibrillary acidic protein (GFAP), detected in the serum of severe TBI patients and CH as measured by brain tissue oxygen partial pressure (Pbo(2)). Patients with severe TBI were prospectively enrolled. Pressure times time (PTD; mm Hg*h), measuring the depth and duration of CH, was calculated for 12-h periods for episodes of moderate (Pbo(2) < 20 mm Hg) and severe (Pbo(2) < 15 mm Hg) CH, and compared to serum levels of S100β, NSE, and GFAP drawn prior to periods of monitoring. An adjusted mixed model analysis was applied as was receiver operating characteristic (ROC) curve analysis. Of 76 patients enrolled, 24 had Pbo(2) monitoring. One hundred and thirty serum samples were matched with 12-h periods of monitoring. Significant associations were found in adjusted analyses between increasing serum levels of S100β (coefficient=0.57, 0.56; p<0.001), NSE (coefficient=0.48, 0.52; p<0.001), and GFAP (coefficient=0.29, 0.30; p=0.003 and 0.002), and increasing PTD of moderate (Pbo(2)<20 mm Hg) and severe (Pbo(2)<15 mm Hg) CH. AUCs for the prediction of moderate and severe CH were 0.62 and 0.66 for S100β, 0.55 and 0.71 for NSE, and 0.50 and 0.62 for GFAP, respectively. Specificities were between 76% and 90% for S100β and NSE. S100β, NSE, and GFAP demonstrate promise as candidate serum markers of impending CH. The fact that these biomarker elevations occur prior to the onset of clinical manifestations suggests that we may be able to predict imminent events following TBI. Given the morbidity of CH, early intervention and prevention may have a significant impact on outcomes and help guide decisions about the timing of interventions.

Background: Neurological injury is a common complication in the early period after liver transplantation, posing an enormous obstacle to treatment efficiency and patient survival. Nicorandil is a mitochondrial ATP-sensitive potassium channel (mitoKATP) opener. It has been reported to be effective in reducing brain injury in recent studies. However, it is still unclear whether nicorandil has cerebral protective effect in patients undergoing liver transplantation., Methods: Fifty patients scheduled for liver transplantation were randomly divided into a nicorandil group (group N) (n=25), in which patients received 10 mg nicorandil through a nasogastric tube 30 minutes before induction of anesthesia, and a control group (group C) (n=25) who received 10 mL normal saline. The Mini-Mental State Examination (MMSE) was performed before anesthesia (day 0), and on days 3 and 7 after surgery. Blood samples were obtained before induction of anesthesia (T1), and at 12 (T2) and 36 hours (T3) after surgery for determination of serum neuron-specific enolase (NSE) and S100β protein (S100β) concentrations., Results: During surgery, 5 patients in each group were eliminated due to severe reperfusion or renal insufficiency. Therefore, 20 patients remained in each group. The MMSE scores after operation were significantly lower than those before operation in group C. However, there was no difference at days 3 and 7 compared with day 0 in group N. Serum NSE concentrations after surgery were significantly higher than baseline (at T1) in both groups, except at T3 in group N. Serum S100β concentration after surgery was significantly higher than baseline (at T1) in both groups. The MMSE scores at days 3 and 7 in group N were significantly higher than those in group C. The concentrations of serum NSE and S100β at T2 and T3 in group N were significantly lower than those in group C., Conclusions: Oral nicorandil, as a premedication before liver transplantation, improves postoperative MMSE scores. It also attenuates the increase of NSE and S100β in blood, indicating its cerebral protective effect.

Object: In this article we tested the hypothesis that the level of two biochemical markers of brain injury may be associated with the apolipoprotein E (APOE) ε4 allele., Methods: In this prospective consecutive study patients with sTBI were included (n = 48). Inclusion criteria were Glasgow Coma Scale (GCS) score ≤ 8 at the time of intubation and sedation, patient age between 15 and 70 years, an initial cerebral perfusion pressure > 10 mmHg, and arrival to our level-one trauma university hospital within 24 h after trauma. Blood samples for neuron-specific enolase (NSE) and S-100B were collected as soon as possibly after arrival, and then twice daily (12-h intervals) for 5 consecutive days. Venous blood was used for APOE genotype determination. Clinical outcome at 3 months after injury was assessed with the Extended Glasgow Outcome Scale (GOSE)., Results: Significantly higher levels of the maximal S-100B (S-100B(max)) and area under the curve (S-100B(AUC)) were found in subjects with the APOE ε4 allele compared to those with non-ε4. A similar tendency was observed for NSE(max) and NSE(AUC), though not statistically significant., Conclusion: Our data indicate that there might be a gene-induced susceptibility to severe traumatic brain injury and that patients with the APOE ε4 allele may be more predisposed to brain cellular damage measured as S-100B and NSE. Thus, it seems to be of importance to consider the APOE genotype in interpreting the levels of the biomarkers.

Objective: To examine the prognostic ability of protein S100B, neuron-specific enolase (NSE) and glial fibrillary acid protein (GFAP) for prediction of 1-year mortality in patients with traumatic brain injury (TBI) in relation to clinical and radiological characteristics of TBI., Methods: Brain injury was quantified in 84 patients (Glasgow Coma Scale [GCS] ≤ 12) using clinical (GCS, pupils), radiological (computed tomography [CT] classification and individual CT characteristics) and biochemical (S100B, NSE and GFAP) data at admission and in the acute post-injury period., Results: Initial and peak S100B, NSE and GFAP concentrations were higher in non-survivors (n = 26) than in survivors (p-value range: <0.001-0.018). Cox regression showed that GFAP and S100B concentration and the temporal profile of S100B were more powerful independent predictors of mortality than baseline clinical and radiological characteristics or clinical and radiological indicators of neurological deterioration. The prognostic models containing admission variables and those available during the subsequent clinical course showed the same discrimination ability (area under receiver characteristic curve 0.92), but the model based on variables available in the acute post-injury period calibrated better (p = 0.428)., Conclusion: Mortality at 1-year post-TBI is accurately predicted by the combination of GFAP and S100B concentration and clinical and radiological characteristics at admission or in the acute post-injury period.

Background: To determine, using a civilian model of mild traumatic brain injury (TBI), the added value of biomarker sampling upon prognostication of outcome at 1 week and 6 weeks postinjury., Methods: The Galveston Orientation and Amnesia test was administered, and blood samples for serum protein S100B and neuron-specific enolase (NSE) were collected from 141 emergency department patients within 4 hours of a suspected mild TBI (mTBI). The Rivermead Post-Concussion Symptoms Questionnaire (RPQ) was administered via telephone 3 days postinjury. Patients were assessed by a physician at 1 week (n = 113; 80%) and 6 weeks (n = 95; 67%) postinjury. Neurocognitive and postural stability measures were also administered at these follow-ups., Results: Levels of S100B and NSE were found to be abnormally elevated in 49% and 65% of patients with TBI, respectively. Sixty-eight percent and 38% of the patients were considered impaired at 1 week and 6 weeks postinjury, respectively. Stepwise logistic regression modeling identified admission Galveston Orientation and Amnesia test score, S100B level, and RPQ score at day 3 postinjury to be predictive of poor outcome at 1 week postinjury (c-statistic 0.877); female gender, loss of consciousness, NSE level, and RPQ score at day 3 postinjury were predictive of poor outcome at 6 weeks postinjury (c-statistic 0.895). The discriminative power of the biomarkers alone was limited., Conclusions: Biomarkers, in conjunction with other readily available determinants of outcome assessed in the acute period after injury, add value in the early prognostication of patients with mTBI. Our findings are consistent with the notion that S100B and NSE point to biological mechanisms underlying poor outcome after mTBI.

Boxing exposes participants to the physiological response to high intensity exercise and also to direct body and brain trauma. Amateur boxing is increasing and females have also been included in the Olympics. The aim of this study is to assess the stress response and possible brain injury incurred during a match by measuring serum biomarkers associated with stress and cellular brain injury before and after combat. Sixteen male amateur boxers were studied retrospectively. The study population was divided into two groups: (a) a group that received predominantly punches to the head (PTH) and (b) a group that received predominantly punches to the body (PTB). Blood samples were taken before and five minutes after each contest. They were analysed for S-100B, neuron-specific enolase (NSE), creatine kinase (CK) and cortisol. The PTH group received direct contacts to the head (not blocked, parried or avoided) and to the body (n=8, age: 17.6 ± 5.3, years; height: 1.68 ± 0.13, meters; mass: 65.4 ± 20.3, kg). The PTB group received punches to the body including blocked and parried punches, but received no direct punches to the head, (n=8, mean ± SD, age: 19.1 ± 3.2 years; height: 1.70 ± 0.75, meters; mass: 68.5 ± 15 kg). Significant increases (P<0.05) were observed between pre- and post-combat serum concentrations in serum concentrations in PTH of S-100B (0.35 ± 0.61 vs. 0.54 ± 0.73, μg.L-1) NSE (19.7 ± 14 vs.31.1 ± 26.6, ng.ml-1) and cortisol (373 ± 202 vs. 756 ± 93, nmol.L-1). Significant increases (P<0.05) of creatine kinase were recorded in both groups. This study demonstrates significant elevations in neurochemical biomarkers in boxers who received direct blows to the head. However, further work is required to quantify this volumetric brain damage and long term clinical sequelae.

Objective: To determine the inflammatory effects of time-dependent exposure to the hypobaric environment of simulated aeromedical evacuation following traumatic brain injury (TBI)., Methods: Mice were subjected to a blunt TBI or sham injury. Righting reflex response (RRR) time was assessed as an indicator of neurologic recovery. Three or 24 h (Early and Delayed groups, respectively) after TBI, mice were exposed to hypobaric flight conditions (Fly) or ground-level control (No Fly) for 5 h. Arterial blood gas samples were obtained from all groups during simulated flight. Serum and cortical brain samples were analyzed for inflammatory cytokines after flight. Neuron specific enolase (NSE) was measured as a serum biomarker of TBI severity., Results: TBI resulted in prolonged RRR time compared with sham injury. After TBI alone, serum levels of interleukin-6 (IL-6) and keratinocyte-derived chemokine (KC) were increased by 6 h post-injury. Simulated flight significantly reduced arterial oxygen saturation levels in the Fly group. Post-injury altitude exposure increased cerebral levels of IL-6 and macrophage inflammatory protein-1α (MIP-1α), as well as serum NSE in the Early but not Delayed Flight group compared to ground-level controls., Conclusions: The hypobaric environment of aeromedical evacuation results in significant hypoxia. Early, but not delayed, exposure to a hypobaric environment following TBI increases the neuroinflammatory response to injury and the severity of secondary brain injury. Optimization of the post-injury time to fly using serum cytokine and biomarker levels may reduce the potential secondary cerebral injury induced by aeromedical evacuation., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Object: Complement activation has been suggested to play a role in the development of secondary injuries following traumatic brain injury (TBI). The present study was initiated in order to analyze complement activation in relation to the primary brain injury and to secondary insults, frequently occurring following TBI., Methods: Twenty patients suffering from severe TBI (Glasgow coma score ≤ 8) were included in the study. The "membrane attack complex," C5b9, which is the cytolytic end product of the complement system was analyzed in cerebrospinal fluid (CSF). The degree of brain tissue damage was assessed using the release of S100B and neuron-specific enolase (NSE) to the CSF and blood. The blood-brain barrier was assessed using the CSF/serum quotient of albumin (Q (A))., Results: Following impact, initial peaks (0-48 h) of C5b9, S100B, and NSE with a concomitant loss of integrity of the blood-brain barrier were observed. Secondary insults at the intensive care unit were monitored. Severe secondary insults were paralleled by a more pronounced complement activation (C5b9 in CSF) as well as increased levels of S100B (measured in CSF), but not with NSE., Conclusion: This human study indicates that complement activation in the brain is triggered not only by the impact of trauma per se but also by the amount of secondary insults that frequently occur at the scene of accident as well as during treatment in the neurointensive care unit. Complement activation and in particular the end product C5b9 may in turn contribute to additional secondary brain injuries by its membrane destructive properties.

Blast-induced traumatic brain injury (TBI) has been the predominant cause of neurotrauma in current military conflicts, and it is also emerging as a potential threat in civilian terrorism. The etiology of TBI, however, is poorly understood. Further study on the mechanisms and treatment of blast injury is urgently needed. We developed a unique rat model to simulate blast effects that commonly occur on the battlefield. An electric detonator with the equivalent of 400 mg TNT was developed as the explosive source. The detonator's peak overpressure and impulse of explosion shock determined the explosion intensity in a distance-dependent manner. Ninety-six male adult Sprague-Dawley rats were randomly divided into four groups: 5-cm, 7.5-cm, 10-cm, and control groups. The rat was fixed in a specially designed cabin with an adjustable aperture showing the frontal, parietal, and occipital parts of the head exposed to explosion; the eyes, ears, mouth, and nose were protected by the cabin. After each explosion, we assessed the physiologic, neuropathologic, and neurobehavioral consequences of blast injury. Changes of brain tissue water content and neuron-specific enolase (NSE) expression were detected. The results in the 7.5-cm group show that 87% rats developed apnea, limb seizure, poor appetite, and limpness. Diffuse subarachnoid hemorrhage and edema could be seen within the brain parenchyma, which showed a loss of integrity. Capillary damage and enlarged intercellular and vascular space in the cortex, along with a tattered nerve fiber were observed. These findings demonstrate that we have provided a reliable and reproducible blast-induced TBI model in rats., (Copyright 2010 Elsevier B.V. All rights reserved.)

Background: Serum glial fibrillary acidic protein (GFAP) is a specific predictor of brain damage and neurologic outcome in patients with traumatic brain injury (TBI). In this study, serum GFAP, S-100B, and neuron-specific enolase (NSE) were compared in the same samples from severe trauma patients to assess their ability to predict abnormalities detectable on head computed tomography (CT)., Methods: This study was a retrospective analysis at a single university emergency center. Thirty-four trauma patients were included. Serum samples were collected from the patients for 3 days. Serum GFAP, S-100B, and NSE concentrations were measured with enzyme-linked immunosorbent assays and compared in patients with and without TBI, as evaluated by head CT., Results: Serum GFAP, S-100B, and NSE were significantly higher in the TBI patients than in the non-TBI patients (p < 0.05 for each protein). The receiver operating characteristic curves for TBI were compared for the three biomarkers for 3 days. Serum GFAP on day 1 had the largest area under the receiver operating characteristic curve (0.983), with 88.9% sensitivity and 100% specificity., Conclusions: Serum GFAP has remarkable diagnostic value for TBI, defined by abnormal head CT findings, in prehospital-triaged patients with severe trauma.