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Arsenic is one of the most important environmental pollutants especially in drinking water. The S100B protein is presented as a sensitive biomarker for assessment of the blood-brain barrier integrity previously. The objective of this study was to determine the impact of chronic arsenic exposure in drinking water and serum S100B correlation. Fifty-four male BALB/c mice were randomly divided into three groups. Group I and II subjects were treated with arsenic trioxide (1 ppm and 10 ppm, respectively), while the rest received normal drinking water. Arsenic concentration in serum and brain was measured by an atomic absorption spectrometer (Varian model 220-Z) conjugated with a graphite furnace atomizer (GTA-110). Also, a serum S100B protein concentration was determined using commercial ELISA kit during different times of exposure. It was observed that body weight gain was significantly lower from the 10th week onwards in arsenic-treated subjects. However, it did not induce any visible clinical signs of toxicity. Measured arsenic level in serum and brain was higher in espoused groups as compared to the control subjects (p < 0.001 and p < 0.0001, respectively). In addition, serum S100B content was increased over a period of 3 months and had significant differences as compared to the control and 1-ppm group especially after 3 months of exposure in the 10-ppm group (p < 0.0001). In conclusion, it could be inferred that long-term arsenic exposure via drinking water leads to brain arsenic accumulation with serum S100B elevated concentration as a probable BBB disruption consequence.

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.

Background: S100-β protein has been introduced as a sensitive biomarker of silent cerebral injury. This study compares its serum levels before, during, and 24 hours after carotid artery stenting (CAS) and carotid endarterectomy (CEA)., Methods: We measured serum level of S100-β in arterial blood before (S100Ba), during (S100Bb), and 24 hours after (S100Bc) CAS and CEA. We assessed differences in S100-β levels using non-parametric tests. We analyzed the relationship between carotid plaque type (echolucency) and S100-β protein level. We also examined its relation to the oximetry results in the CEA group (ipsilateral and contralateral)., Results: Thirty patients were enrolled, including 15 CAS and 15 CEA patients, with no significant differences in baseline atherosclerotic characteristics. There was no significant difference in S100Ba or S100Bb levels between CAS and CEA patients. However, a significant difference was found in S100Bc: 331.3 pg/mL (IQ range 56.4-583.5) for CAS vs. 76.3 pg/mL (IQ range 29.7-117.4) for CEA (P=0.01). Type I and II plaques were associated with the higher S100Bc levels in CAS (P=0.048). S100Bc was higher in CEA patients when the contralateral cerebral hemisphere had oximetry values less than 60% (P=0.043)., Conclusions: Our study suggests that CAS might produce silent brain injury. Moreover, vulnerable plaques might be associated with higher levels of S100-β protein, especially in CAS. This pilot study demonstrates that S100-β is a useful biomarker for silent brain injury in carotid revascularization. Large scale studies are still needed to confirm these findings.

Major depressive disorder (MDD) is the most common nonfatal disease burden worldwide. Systemic chronic low-grade inflammation has been reported to be associated with MDD progression by affecting monoaminergic and glutamatergic neurotransmission. However, whether various proinflammatory cytokines are abnormally elevated before the first episode of depression is still largely unclear. Here, we evaluated 184 adolescent patients who were experiencing their first episode of depressive disorder, and the same number of healthy individuals was included as controls. We tested the serum levels of high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-α (TNF-α), IgE, 14 different types of food antigen-specific IgG, histamine, homocysteine, S100 calcium-binding protein B, and diamine oxidase. We were not able to find any significant differences in the serum levels of hs-CRP or TNF-α between the two groups. However, the histamine level of the patients (12.35 μM) was significantly higher than that of the controls (9.73 μM, P < 0.001, Mann-Whitney U test). Moreover, significantly higher serum food antigen-specific IgG positive rates were also found in the patient group. Furthermore, over 80% of patients exhibited prolonged food intolerance with elevated levels of serum histamine, leading to hyperpermeability of the blood-brain barrier, which has previously been implicated in the pathogenesis of MDD. Hence, prolonged high levels of serum histamine could be a risk factor for depressive disorders, and antihistamine release might represent a novel therapeutic strategy for depression treatment., (Copyright © 2019 The Authors. Production and hosting by Elsevier B.V. All rights reserved.)

Objective: To determine the comparative effect of monosialoganglioside versus citicoline on the content changes of serum apoptotic factors (PDCD5, sFas and sFasL), neurological function indices (BDNF, NSE, S100-β and NGF) and oxidative stress indices (SOD, MDA and GSH-PX) in newborns with hypoxic-ischemic encephalopathy (HIE)., Study Design: An experimental study., Place and Duration of Study: Emergency Department, Affiliated Children's Hospital of Zhengzhou University, China, from October 2016 to February 2018., Methodology: A total of 90 newborns with HIE were randomly divided into a treatment group and a control group, with 45 cases in each group. In addition to the conventional treatment, the treatment group was given monosialoganglioside treatment, while the control group was given citicoline treatment. Both groups were treated for 10 days. After treatment, the content differences of serum apoptosis factors (PDCD5, sFas and sFasL), neurological function indices (BDNF, NSE, S100-β and NGF) and oxidative stress indices (SOD, MDA and GSH-PX) were observed in the two groups., Results: After treatment, the levels of serum PDCD5, sFas, sFasL, MDA, NSE and S100-β in the treatment group were lower than those in the control group (all p<0.001). The contents of serum SOD, GSH-PX, BDNF and NGF in the treatment group were higher than those in the control group (all p<0.001)., Conclusion: Monosialoganglioside can effectively improve the apoptotic factors, neurological function and oxidative stress indices in newborns and maintain the stability of the internal environment, so it is worthy of promotion and application.

Aims: S100B has been proposed as a consolidated marker of brain damage in infants with congenital heart disease (CHD) undergoing cardiac surgery and cardiopulmonary bypass (CPB). The present study aimed to investigate whether S100B blood levels in the perioperative period differed in infants complicated or not by cyanotic CHD (CHDc) and correlated with oxygenation status (PaO 2 )., Methods: We conducted a case-control study of 48 CHD infants without pre-existing neurological disorders undergoing surgical repair and CPB. 24 infants were CHDc and 24 were CHD controls. Blood samples for S100B assessment were collected at six monitoring time-points: before the surgical procedure (T0), after sternotomy but before CPB (T1), at the end of the cross-clamp CPB phase (T2), at the end of CPB (T3), at the end of the surgical procedure (T4), at 24 h postsurgery (T5)., Results: In the CHDc group, S100B multiples of median (MoM) were significantly higher (p < .05, for all) from T0 to T5. PaO 2 was significantly lower (p < .05, for all) in CHDc infants at T0-T1 and at T4 while no differences (p > .05, for all) were found at T2, T3, T5. Linear regression analysis showed a positive correlation between S100B MoM at T3 and PaO 2 (R = 0.84; p < .001)., Conclusions: The present data showing higher hypoxia/hyperoxia-mediated S100B concentrations in CHDc infants suggest that CHDc are more prone to perioperative brain stress/damage and suggest the usefulness of further investigations to detect the "optimal" PaO 2 target in order to avoid the side effects associated with reoxygenation during CPB.

Background: Survival following cardiac arrest (CA) and subsequent cardiopulmonary resuscitation (CPR), to a great extent, depends on brain damage. Adipose-derived stem cells (ADSCs), as a source of paracrine growth factors and the capacity of neural differentiation may reduce this brain damage., Objective: The purpose of this study is to evaluate the protection of ADSCs to brain damage following CPR., Methods: Rats were divided into 3 groups, sham, CA, and ADSCs group. Rats in sham group went through sham surgery. Rats in CA group went through CA, CPR, and injection PBS (phosphate buffer saline). Rats in ADSCs group went through CA, CPR, and intravenous injection of ADSCs. Rats in sham group were sacrificed immediately after operation. At 24, 72, and 168 hours after return of spontaneous circulation operation, rats in CA and ADSCs group were randomly selected and sacrificed. Brain damage was evaluated by using Neurological Deficit Scale (NDS) score, hippocampal pathology, serum level of S100β, and apoptosis ratio of hippocampal neurons. Protein of brain derived neurotrophic factor (BDNF) and IL-6 (interleukin-6) in the hippocampus were detected., Results: Compared with sham group, CA and ADSCs group showed a decrease in NDS score, an increased apoptosis ratio of hippocampal nerve cells, increased serum level of S100-β, and a significant increase in neuroprotective IL-6 and BDNF. In comparison to CA group, ADSCs group had a mild degree of brain damage and higher expression of IL-6 and BDNF., Conclusions: In the acute stage of cerebral injury following CA, ADSCs might improve the prognosis of brain damage by stimulating the expression of neuroprotective IL-6 and BDNF., (Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Background: A noninvasive biomarker is needed to predict recovery from severe spinal cord injury (SCI) because of thoracolumbar intervertebral disc extrusion (TL-IVDE). Proteins released from neural and glial cells can be detected in the blood and show promise as prognostic tools, but their concentration is influenced by time after injury., Hypothesis/objectives: Serum concentrations of glial fibrillary acidic protein (GFAP), phosphorylated neurofilament heavy chain (pNFH), and S100β will follow different time courses; measurement of combinations of these proteins will predict outcome., Animals: Thirty-one dogs with TL-IVDE causing paralysis with no pain perception., Methods: Prospective study. Serum samples were taken at presentation and intervals over 56 days and banked at -80°C. Glial fibrillary acidic protein, pNFH, and S100β concentrations were measured using ELISA tests and plotted against time from onset of nonambulatory status. Outcome was established at 6 months. The association between biomarker concentration and outcome was examined using logistic regression, receiver operator characteristics curve analysis, and model development., Results: Thirty-one dogs participated, 3/31 (10%) developed progressive myelomalacia and 19/31 (62%) recovered ambulation. Glial fibrillary acidic protein and S100β concentrations rose for the first 1 to 3 days, and were undetectable by 14 and 28 days, respectively. Phosphorylated neurofilament heavy chain concentrations peaked at 14 days and were detectable at 56 days. Glial fibrillary acidic protein concentrations in the first 72 hours after onset of nonambulatory status predicted recovery with an accuracy of 76.7%-89% depending on sample timing., Conclusions and Clinical Importance: Serum GFAP concentrations can be used to predict outcome in clinically complete SCI. A rapid inexpensive bedside test is needed., (© 2019 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

Validated serum biomarkers for patients suffering from non-small cell lung cancer (NSCLC) brain metastasis are urgently needed for early diagnosis, treatment monitoring, and prognostic classification in daily clinical practice. Serum S100B was reported to be a marker of leaky blood-brain barrier (BBB), which was often caused by brain tumors. This study aimed to investigate the role of S100B in NSCLC brain metastasis. The results showed that serum S100B correlated significantly with NSCLC brain metastasis (P < 0.001). When evaluated by the ROC curve, at the cutoff point 13.83 pg/ml, the sensitivity and specificity were 94% and 93%, respectively (AUC= 0.938, P < 0.001). High level of serum S100B was significantly correlated with a higher number of brain metastases and significantly worse prognosis (P <  0.05). In addition, S100B was an independent prognostic factor (P <  0.001). In conclusion, serum S100B was a sensitive and specific marker for early detection of brain metastasis in NSCLC and could be used as a surveillance tool for prognosis evaluation., (Copyright © 2018. Published by Elsevier GmbH.)

Magnetic resonance imaging (MRI) studies have consistently identified a high incidence of silent brain infarction (SBI) after cardiac intervention. The frequent occurrence, objective measurement and clinical sequelae of SBI have seen interest in their detection for both research and clinical purposes. However, MRI is expensive, time-consuming, unsafe in acutely-ill patients, and not always available, limiting its use as a routine screening tool. For this purpose, a blood biomarker of SBI would be the "Holy Grail." By performing targeted profiling of serologic biomarkers this study aimed to assess their potential as screening tools for perioperative SBI. This is a nested case-control study of 20 prospectively recruited patients undergoing transcatheter aortic valve implantation under general anesthesia. Clinical and diffusion-weighted MRI assessments were performed at baseline and on day 3 postprocedure to identify the presence (cases) or absence (controls) of new SBI. Blood was collected at baseline and 24, 48, and 72 hours postprocedure and analyzed for S100 calcium-binding protein B, neuron specific enolase (NSE), matrix metalloproteinase 9 (MMP 9), and glial fibrillary acidic protein. Best-fit polynomial curves using a smoothing model were generated for each biomarker and inferential testing at a predefined 24-hour postprocedure timepoint detected a significant difference for MMP 9 (72,435; SEM: 25,030; p = 0.027). Longitudinal regression revealed a statistically significant case-control difference for both NSE (mean: 10,747; SEM: 3,114) and MMP 9 (63,842; SEM: 16,173). In conclusion, NSE and MMP 9 are present in higher levels following SBI and warrant further investigation for their utility as screening tools., (Copyright © 2018. Published by Elsevier Inc.)

The blood-brain barrier (BBB) disruption is a critical step in paraneoplastic neurological syndrome (PNS) development. Several cytokines have been implicated in BBB breakdown. However, the exact step-by-step mechanism in which PNS develops is unknown, and the relationship between a systemic neoplasm and BBB is multilevel. The aim of the present study was to examine serum markers of BBB breakdown (S100B protein, neuron-specific enolase, NSE) and concentrations of proinflammatory (TNF-alpha, VEGF) and anti-inflammatory/immunosuppressive cytokines (IL-4), and to establish their interrelationship in patients with PNS. We analyzed 84 patients seropositive for onconeural antibodies that originated from a cohort of 250 cases with suspected PNS. Onconeural antibodies were estimated with indirect immunofluorescence and confirmed with Western blotting. Serum S-100B was estimated using electrochemiluminescence immunoassay. NSE, VEGF, TNF-alpha and IL-4 were analyzed with ELISA. We found that S-100B protein and NSE serum concentrations were elevated in PNS patients without diagnosed malignancy, and S-100B additionally in patients with peripheral nervous system manifestation of PNS. Serum VEGF levels showed several abnormalities, including a decrease in anti-Hu positive patients and increase in PNS patients with typical manifestation and/or central nervous system involvement. Increase in TNF-alpha was observed in patients with undetermined antibodies. To conclude, the presence of paraneoplastic neurological syndrome in seropositive patients does not affect serum markers of BBB breakdown, with the exception of the group without clinically demonstrated malignancy and patients with peripheral manifestation of PNS. S-100B and NSE might increase during early phase of PNS. VEGF may be involved in typical PNS pathophysiology.

This study aimed to determine whether the combination of procalcitonin (PCT) and S100B improves prognostic performance compared to either alone in cardiac arrest (CA) patients treated with targeted temperature management (TTM).We performed a prospective cohort study of CA patients treated with TTM. PCT and S100B levels were obtained at 0, 24, 48, and 72 hours after return of spontaneous circulation. The prognostic performance was analyzed using each marker and the combination of the 2 markers for predicting poor neurological outcome at 3 months and mortality at 14 days and 3 months.A total of 97 patients were enrolled, of which 67 (69.1%) had poor neurological outcome. S100B showed a better prognostic performance (area under the curve [AUC], 0.934; sensitivity, 77.6%; and specificity, 100%) than PCT (AUC, 0.861; sensitivity, 70.2%; and specificity, 83.3%) with the highest prognostic value at 24 hours. The combination of 24-hour PCT and S100B values (S100B ≥0.2 μg/L or PCT ≥6.6 ng/mL) improved sensitivity (85.07%) compared with S100B alone. In multivariate analysis, PCT was associated with mortality at 14 days (odds ratio [OR]: 1.064, 95% confidence interval [CI]: 1.014-1.118), whereas S100B was associated with neurological outcomes at 3 months (OR: 9.849, 95% CI: 2.089-46.431).The combination of PCT and S100B improved prognostic performance compared to the use of either biomarker alone in CA patient treated with TTM. Further studies that will identify the optimal cutoff values for these biomarkers must be conducted.

Objective: To assess the value of postictal serum Ubiquitin C-terminal hydrolase (UCHL-1), a neuronal biomarker, and S100-B, a glial biomarker, levels, in differentiate epileptic seizures (ES) form psychogenic attacks., Methods: In this analytical cross-sectional study, serum UCHL-1 and S100-B levels were measured within six hours of occurring seizure, in 43 patients with ES, 20 patients with psychogenic non-epileptic seizures (PNES) and 19 healthy individuals by electrochemiluminescence immunoassay., Results: Both serum UCHL-1 and S100-B levels were significantly higher in patients with ES than PNES (P < 0.05) and controls (P < 0.01). PNES patients had significantly higher serum S100-B levels compared to controls (P < 0.01). There was a significant correlation between the serum UCHL-1 and S100-B levels in patients with ES (r = 0.46, P = 0.002)., Conclusions: Our study showed that serum UCHL-1 level could be potentially used in differentiate ES from PNES (sensitivity 72%, specificity 59%). Serum S100-B level had lower value compared to UCHL-1 (AUC 0.68 for UCHL-1 v/s 0.59 for S100B). Post-seizure serum UCHL-1 and S100-B levels could be used in future studies to better understand the underlying mechanism of seizures and may offer as an adjunctive diagnostic test in differentiate ES from PNES., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Purpose: Increased serum biomakers, such as S100 calcium-binding protein B (S100B) and neuron-specific enolase (NSE), are associated with traumatic brain injury (TBI). The purpose of this study is to investigate the serum levels of S100B and NSE in pediatric TBI patients and to predict a clinical outcome., Methods: Peripheral venous blood was collected within 6 h of injury and at 1 week to measure S100B and NSE. The serum S100B and NSE levels were measured using commercially available enzyme-linked immunosorbent assay kits. The authors divided participants into two groups at admission: a favorable group (patients with Glasgow Coma Scale [GCS] scores of 10-15) and an unfavorable group (patients with GCS scores of less than 9). Both S100B and NSE levels were compared between the two groups at the time of admission and 1 week later., Results: Ten pediatric patients were enrolled (5 in the favorable group, 5 in the unfavorable group). The median serum S100B level of 134.21 pg/ml (range, 51.00-789.65 pg/ml) in patients with TBI at admission dropped to 41.49 pg/ml (range, 25.65-260.93 pg/ml) after 1 week, with significant differences between the traumatic event and 1 week later (p = 0.007). The median serum NSE level of 14.76 ng/ml (range, 6.48-21.23 ng/ml) in patients with TBI at admission was higher than that after 1 week (4.96 ng/ml, range, 3.01-31.21 ng/ml), with significant differences (p = 0.015). A significant difference was observed in S100B after 1 week between patients in the favorable and unfavorable groups (p = 0.047). One patient whose serum S100B and NSE levels were elevated 1 week after TBI eventually died., Conclusions: Elevated serum S100B and NSE levels in pediatric TBI patients decreased 1 week after traumatic events. The serum S100B level 1 week after TBI was related to the severity of brain damage. These results indicated that serum S100B and NSE might play a role in predicting the prognosis and monitoring ongoing brain injury in pediatric TBI patients.

Sepsis-associated encephalopathy (SAE) has significant impact on the neurocognitive outcome of sepsis survivors. This study was conducted to analyze the amino-terminal propeptide of the C-type natriuretic peptide (NT-proCNP) as a biomarker for SAE in comparison to neuron-specific enolase (NSE) and S100B protein. Cerebrospinal fluid (CSF) and plasma samples from twelve septic patients with SAE and nine non-septic controls without encephalopathy were analyzed. The assessment of SAE comprised a neuropsychiatric examination, delirium screening using the confusion assessment method in the ICU (CAM-ICU) and magnetic resonance imaging (MRI) in all participants. NSE, S100B and NT-proCNP were measured in plasma at study days 1, 3 and 7 in sepsis patients, once in controls and once in the CSF of both groups. The long-term outcome was assessed using the validated Barthel index (BI). Plasma NT-proCNP levels were significantly higher in the sepsis cohort compared to controls with peak concentrations at study day 1 (10.1 ± 6.6 pmol/l vs. 3.3 ± 0.9 pmol/l; p < 0.01) and a decrease over time. Plasma NT-proCNP levels at day 7 correlated with NT-proCNP in CSF (r = 0.700, p < 0.05). A comparable decrease of significantly higher plasma S100B values in sepsis patients compared to controls was observed. Plasma NSE levels were not significantly different between both groups. CSF NT-proCNP levels just tended to be higher in sepsis patients compared to controls and tended to be higher in patients with septic brain lesions seen on MRI. In the sepsis cohort CSF NT-proCNP levels correlated with CSF Interleukin-6 (IL-6) levels (r = 0.616, p < 0.05) and systemic inflammation represented by high plasma procalcitonin (PCT) levels at day 3 (r = 0.727, p < 0.05). The high peak concentration of plasma NT-proCNP in the early phase of sepsis might help to predict the emergence of SAE during the further course of disease. NT-proCNP in plasma might, in contrast to CSF, indicate neurological impairment in patients with SAE., (Copyright © 2018 Elsevier B.V. All rights reserved.)

BACKGROUND The incidence of postoperative cognitive dysfunction (POCD) after major joint arthroplasty is high. In the etiology of POCD, many factors have been cited, including thromboembolic complications. The incidence of cerebral embolization after lower extremity arthroplasty may be as high as 40-60%. The potential events of cerebral embolization could lead to a decrease in the regional cerebral oxygenation (rSO2) and increased serum levels of biochemical markers of brain damage. The objective of the study was to test whether there are any changes in the rSO2 values and serum markers of brain damage in patients who underwent total hip arthroplasty. MATERIAL AND METHODS Fifteen patients who underwent primary hip arthroplasty under spinal anesthesia were analyzed. The rSO2 was monitored using infrared spectroscopy. Biochemical analyses of S100 calcium-binding protein B (S100B) protein and fibrillary acidic protein (GFAP) serum concentrations were performed using immunoassay methods. RESULTS The values of rSO2 decreased during the surgery, but this was not related to mean arterial pressure variations or hemoglobin saturation. The concentration of S100B was increased compared to its preoperative values, and there were no changes in GFAP values. The changes in rSO2 readings correlated with the biomarkers' levels just after the surgery. CONCLUSIONS Our results suggest that S100B may be a more specific marker of astroglial damage in patients after primary total hip arthroplasty. The decrease in rSO2 readings may be due to micro-thromboembolic events that occurred during the surgery. However, the results of this study are preliminary, and further studies are needed to establish its clinical efficacy.

S100B is a calcium-binding protein most abundant in neuronal tissue. It is expressed in glial cells and Schwann cells and exerts both intra- and extracellular effects. Depending on the concentration, secreted S100B exerts either trophic or toxic effects. Its functions have been extensively studied but are still not fully understood. It can be measured in cerebrospinal fluid and in blood, and increased S100B level in blood can be seen after, e.g., traumatic brain injury, certain neurodegenerative disorders, and malignant melanoma. This chapter provides a short background of protein S100B, commercially available methods of analysis, and its clinical use, especially as a biomarker in minor head injury.

Background: A high prevalence of delirium is observed in sepsis, yet specific markers for this brain dysfunction in sedated patients are still lacking. Cytoplasmic low molecular weight calcium-binding protein, S-100β, is a commonly used nonspecific marker for brain injury. Here, we evaluated whether delirium is associated with increases in S-100β levels., Methods: This observational study included 22 patients with septic shock. Delirium was assessed by CAM-ICU and blood samples were obtained to measure inflammatory (CRP, PCT, IL-6, IL-17, TNF-α) and cerebral biomarkers (S-100β, NSE, HAB42, SUBP). Patients were categorized according to the presence of delirium., Results: Delirium was present in 10/22 of the patients (45.5%). Serum S-100β levels were above the laboratory cutoff value of 0.15 μg/L in 13/22 (59.1%) of the patients. The odds ratio for risk of developing delirium in cases with an S-100β >0.15 μg/L was 18.0 (95%CI, 1.7-196.3, P = 0.011). Patients with delirium had higher plasma levels of IL-6 compared to those without; 138.3 pg/mL [28.0-296.7] vs 53.6 pg/mL [109.3-505, P = 0.050]. There was a positive correlation between S100 β and IL-6 levels (r = 0.489, P = 0.021). Delirium patients had higher SOFA scores; 10 [5-9] vs 7[8-10.5], P = 0.036., Conclusions: Delirium in septic shock was associated with an elevated protein S-100β when using a laboratory cutoff value of 0.15 μg/L and with more severe organ dysfunction during the ICU stay., (© 2018 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Aim: To evaluate the plasma content of S100B protein in children with autism spectrum disorders (ASD)., Material and Methods: Forty-five children with autism (item F84 of ICD-10), aged from 6 to 15 years, were examined. The control group (KG) consisted of 25 healthy children. The study included examination by specialists, an assessment of the severity of the disease using the Children's Rating Scale of Autism scale (CARS), evaluation of S100B in blood serum., Results: The content of S100B in children with autism was significantly higher in comparison with KG. The level of S100B in children with ASD with abnormal development of brain structures (MRI) was significantly higher compared with KG and a group of children without signs of disturbance of brain structures. S100B levels were higher in children with severe ASD, and differed from controls in children with moderate ASD., Conclusion: The majority of children with ASD show signs of stress of neuroprotective mechanisms, and children with anomalies of brain structures have signs of hypoxia of the brain and damage of the blood-brain barrier.

Objectives: Our aim is to describe changes in serum concentration for the pro-inflammatory factors TNF-α, IFN-γ, IL-1β, IL-8, IL-6, IL-10, IL-12 and MCP-1, for the satiety factor leptin and for factors associated with neuronal changes, neuron-specific enolase (NSE) and glial activation S100-beta protein (S100-β), and explore their association with abstinence in alcohol-dependent subjects after withdrawal., Methods: Serum sampling and clinical assessments from 115 alcohol-dependent subjects admitted to a psychiatric hospital for alcohol were repeated during the first 48 h of withdrawal (M0) and 1, 2, 4 and 6 months (M1, M2, M4 and M6) thereafter. Serum factors were determined with Luminex technology or by ELISA., Results: The levels of TNF-α, IL-1β, IL-8, IL-6, IL-12, MCP-1, and leptin decreased after withdrawal and remained low until M6, regardless of alcohol consumption. IFN-γ levels remained constant and IL-10 levels changed only slightly. NSE levels were not modified, whereas serum S100-β concentration increased significantly on M1 and then plateaued, regardless of abstinence status at 6 months., Conclusions: Alcohol-dependent subjects present an inflammatory condition that is not dependent on alcohol consumption. An understanding of the changes in concentration of the various proteins considered here would provide insight into the physiology of withdrawal or dependence.

The Centers for Disease Control and Prevention estimates almost two million traumatic brain injuries (TBIs) occur annually in the U.S., resulting in nearly $80 billion of economic burden. Despite its prevalence, current TBI diagnosis methods mainly rely on cognitive assessments vulnerable to subjective interpretation, thus highlighting the critical need to develop effective unbiased diagnostic methods. The presented study aims to assess the feasibility of a rapid multianalyte TBI blood diagnostic. Specifically, two electrochemical impedance techniques were used to evaluate four biomarkers: glial fibrillary acidic protein, neuron specific enolase (NSE), S-100β, and tumor necrosis factor-α. First, these biomarkers were characterized in purified solutions (detection limit, DL = 2-5 pg/mL), then verified in spiked whole blood and plasma solutions (90% whole blood DL = 14-67 pg/mL). Finally, detection of two of these biomarkers was validated in a controlled cortical impact model of TBI in rats, where a statistical difference between NSE and S-100β concentrations differed several days postinjury (p = 0.02 and p = 0.06, respectively). A statistical difference between mild and moderate injury was found at the various time points. The proposed diagnostic method enabled preliminary quantification of TBI-relevant biomarkers in complex media without the use of expensive electrode coatings or membranes. Collectively, these data demonstrate the feasibility of using electrochemical impedance techniques to rapidly detect TBI biomarkers and lay the groundwork for development of a novel method for quantitative diagnostics of TBI.

Malignant melanoma is a cancer with increasing incidence worldwide with relevant socioeconomic impact. Despite progress in prevention and early detection, it is one of the most lethal forms of skin cancer. Therefore it is urgent need to identify suitable biomarkers in order to improve early diagnosis, precise staging, and prognosis, as well as for therapy selection and monitoring. In this book chapter, we are focusing on S100B and discuss its clinical relevance in melanoma.

Purpose: Long standing temporal lobe epilepsy (TLE) causes cerebral insult and results in elevated brain injury biomarkers, S100b and neuron specific enolase (NSE). Surgery for TLE, has the potential to cause additional cerebral insult. Dexmedetomidine is postulated to have neuroprotective effects. The aim of this study was to assess the effect of intraoperative dexmedetomidine on S100b and NSE during TLE surgery., Materials and Methods: 19 consenting adult patients with TLE undergoing anteromedial temporal lobectomy were enrolled and divided into two groups. Patients in Group D (n = 9) received dexmedetomidine whereas patients in Group C (n = 10) received saline as placebo in addition to the standard anaesthesia technique. Blood samples of these patients were drawn, before induction of anaesthesia, at the end of surgery, as well at 24 hours and 48 hours postoperatively, and analysed for serum S100b and NSE., Results: The demographic and clinical profile was comparable in both the groups. The baseline S100b in group C and group D was 66.7 ± 26.5 pg/ml and 34.3 ± 21.7 pg/ml (P = 0.013) respectively. After adjustment for the baseline, the overall value of S100b was 71.0 ± 39.8 pg/ml and 40.5 ± 22.5 pg/ml (P = 0.002) in the control and study group, respectively. The values of S100b (79.3 ± 53.6 pg/ml) [P = 0.017] were highest at 24 hours postoperatively. The mean value of NSE in the control and study group was 32.8 ± 43.4 ng/ml (log 3.0 ± 0.1) and 13.51 ± 9.12 ng/ml (log 2.42 ± 0.60), respectively. The value of NSE in both the groups was comparable at different time points., Conclusions: Lower perioperative values of S100b were observed in patients who received intraoperative dexmedetomidine. Dexmedetomidine may play a role in cerebroprotection during epilepsy surgery., Competing Interests: None

Aim: To investigate possible correlations between serum S100B levels and microglial/astrocytic activation in status epilepticus (SE) in lithium-pilocarpine-exposed rat hippocampi and whether serum S100B levels linearly reflect neuroinflammation. Additionally, to assess the effects of minocycline (M), an inhibitor of neuroinflammation., Material and Methods: Rats were divided into 4 groups (6/group), namely, control (C), sham, SE, and SE+M. Animals were exposed to lithium-pilocarpine to induce SE in the SE and SE+M groups. Cardiac blood was collected to measure S100B levels, and coronal brain sections including the hippocampus were prepared to examine microglial/astrocytic activation and to evaluate neuroinflammation at day 7 of SE., Results: Serum S100B levels, OX42 (+) microglia in CA1, and GFAP (+) astrocytes in both CA1 and dentate gyrus (DG) were higher in the SE+M group than in the C group. Most importantly, highly positive correlations were found between S100B levels and microglial activation in CA1, apart from astrocytic activation in CA1 and DG. Unexpectedly, microglial activation in CA1 and astrocytic activation in DG were also enhanced in the SE+M group compared with the C group. Moreover, M administration reversed the neuronal loss observed in DG during SE., Conclusion: These results suggest that serum S100B is a candidate biomarker for monitoring neuroinflammation and that it may also help predict diagnosis and prognosis.

In recent decades a significant scientific effort has focused on projects regarding the use of neurobiomarkers in perinatal medicine with a view to understanding the mechanisms that interfere with physiological patterns of brain development and lead to ominous effects in several human diseases. Numerous potential neurobiomarkers have been proposed for use in monitoring high-risk fetuses and newborns, including markers of oxidative stress, neuroproteins, and vasoactive agents. Nonetheless, the use of these markers in clinical practice remains a matter of debate. Recently, the calcium-binding S100B protein has been proposed as being an ideal neurobiomarker, thanks to its simple availability and easy reproducibility, to the possibility of detecting it noninvasively in biological fluids with good reproducibility, and to the possibility of a longitudinal evaluation in relation to reference curves. The present chapter contains an overview of the most significant studies on the assessment of S100B in different biological fluids as a trophic factor and/or marker of brain damage in high-risk fetuses and newborns.

Background: Neonatal hypoxic ischemic encephalopathy (HIE) is a potentially devastating disorder associated with significant mortality and long-term morbidity., Objective: The aim of this study was to study the role of vitamin D as an adjuvant therapy for management of neonatal HIE., Patients and Methods: This study was carried out on 60 neonates with HIE grade II who were diagnosed according to modified Sarnat staging and were divided in to 2 groups: Group I: Included 30 neonates with Sarnat grade II HIE who received single daily oral dose of vitamin D3 (1000 IU) for 2 weeks in addition to daily subcutaneous (SC) human recombinant erythropoietin (2500 IU/kg) for 5 days and IM or IV magnesium sulphate 250 mg/kg within half an hour of birth, and subsequently 125 mg/kg at 24 and 48 hours of life. Group II: Included 30 neonates with HIE grade II who received erythropoietin and magnesium sulphate as group I but without vitamin D. Two blood samples were taken from all neonates included in both groups; the 1st at diagnosis and the 2nd after 2 weeks of therapy. This study included also 30 healthy neonates as a control group. All neonates included in this study were subjected to: complete clinical examination with assessment of Apgar score at 5 and 10 minutes, measurement of arterial blood gases and serum 25 (OH) vitamin D, calcium, phosphorus, S100-B and IL-17 levels., Results: Before therapy, there were no significant differences between group I and II in PH, PO2 and PCO2 (p= 0.294, 0.462, 0.758 respectively), but after 2 weeks of therapy, there were significantly higher PH levels in group I compared with group II (p <0.001) while there were no significant differences between group I and II regarding PO2 and PCO2. Before therapy, there were no significant differences in serum 25(OH) vitamin D levels between group I and II while there were significantly lower serum 25(OH) vitamin D levels in group I and II compared with controls (P1; comparison between group I and II = 0.742, P2; comparison between group I and controls = 0.001 and P3; comparison between group II and controls = 0. 001). There were no significant differences between group I and II and between group I and II and control as regard serum calcium (P1= 0.943, P2= 0.875 and P3= 0.764) and phosphorus (P1= 0.862, P2= 0.921, P3= 0.786). There were no significant differences between group I and II regarding serum IL-17 levels while there were significantly lower serum IL-17 levels in group I and II compared with controls (P1 = 0.457, P2 = 0.043 and P3 = 0.023). Before therapy, there were no significant differences in serum S100-B levels between group I and II while there were significantly higher serum S100-B levels in group I and II compared with control (P1 = 0.381, P2 = 0.001 and P3= 0.001) but after therapy, there were significantly higher S100-B levels in group II compared with group I and significantly higher S100-B levels in group I and II compared with control (P1= 0.001, P2= 0.043, P3 = 0.001). There were significant negative correlations in group I between serum S100-B and PH and between S100-B and serum vitamin D before and after therapy., Conclusion: Vitamin D was found to improve the cases of group I as demonstrated by the reduction of serum S100-B levels after vitamin D therapy., Recommendations: Extensive multicenter studies are required on a large number of patients with Sarnat grade II HIE with longer duration of follow up to give valid recommendations about the use of vitamin D as an adjuvant therapy in Sarnat grade II HIE., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Introduction: Repetitive subconcussive head impacts in contact/collision sports such as in US football are believed to contribute to long-term brain changes and chronic symptoms. However, the lack of tools to measure the effects of repeated subconcussion limits our understanding of potential contributions to neuropathological alterations including cellular damage., Methods: We examined subconcussive head impacts using an accelerometer-embedded mouthguard on changes in blood levels of neurofilament light (NFL) chain in 18 Division I college football players. Plasma levels of NFL and clinical symptoms were assessed at pre-post practices. The frequency and linear and rotational head accelerations recorded via the mouthguard were examined in relation to NFL plasma changes., Results: The frequency and magnitude of head impacts associated with increased NFL levels. The greater numbers of hits and head accelerations associated with greater pre- to post-practice NFL level increases (p < 0.05). Greater pre- to post-practice increases in NFL also associated with greater pre- to post-practice increases in S100β (p < 0.001), but not with total tau. Years of football experience and concussion history did not associate with changes in NFL., Conclusion: Acute changes in NFL may be a clinically useful peripheral marker in tracking acute brain damage in collegiate football players, and other contact sports.

Background: The detection of minute amounts of protein biomarkers in body fluids is believed to provide early diagnosis and prognosis of mild traumatic brain injury (mTBI). An ultrasensitive detection method was used to detect S100B, the most studied potential marker for the diagnosis of mTBI., Methods: The detection method was a modified electrochemical immunoassay technique that provides voltage controlled intrinsic current signal amplification. The sandwich immune complex of S100B was formed on the working electrode of the screen-printed electrode. The gating voltage provides amplification of the current signal that flows through the complex., Results: S100B was spiked in human serum. The limit of detection of S100B in human serum was 10 fg/mL. The calibration curves cover four orders of magnitudes from 10 fg/mL to 10 ng/mL. The specificity of the detection was demonstrated using TAU protein, which is another marker for mTBI., Conclusion: The results reported in this work using the field effect enzymatic detection (FEED)-based immunoassay indicate the feasibility of using this method for the detection of extremely low concentrations of markers of mTBI in human serum. This method can be developed as a platform for a range of markers of mTBI.

The S-100β levels are associated with a variety of acute disorders and other chronic diseases, such as head injury, stroke, metastatic melanoma, cardiac surgery, bone fractures, burns and contusions. The serum S-100β levels seem to increase with the volume of tissue damage. Higher serum S-100β levels have been observed after brain damage or stroke. A number of studies have evidenced the clinical value of S-100β in the diagnosis and prognosis of stroke while the S-100β marker is elevated in the peripheral blood during the acute phase of stroke. However, the clinical usefulness of S-100β biomarker in the diagnosis and prognosis of stroke has a limitation due to its low discriminating ability in stroke diagnosis and prognosis.

Background: Glial fibrillary acidic protein (GFAP) is a brain-specific astroglial protein that is released into the blood soon after traumatic brain injury by mature astrocytes. S100B is rapidly released into the cerebrospinal fluid and bloodstream after brain damage. We compared the serum concentrations of these proteins in patients with severe head trauma (bleeding and/or fracture) or nontraumatic intracerebral hemorrhage and healthy individuals., Materials and Methods: The study included 63 patients (33 males and 30 females) with traumatic cerebral hemorrhage and/or cranial bone fractures or nontraumatic cerebral hemorrhage and 30 healthy control subjects. The reasons for attending the emergency department were as follows: fall from a height (n = 32), traffic accident (n = 18), nontraumatic intracerebral hemorrhage (n = 6), animal kick to the head (n = 4), and blow to the head (n = 3)., Results: Of the 63 patients included in the study, 33 (52.4%) were male and 30 (47.6%) were female. Of the 30 healthy controls, 12 (40%) were male and 18 (60%) were female. The average age of the patients was 27 years (range, 1 month to 86 years) and the average age of the control group was 21 years (range, 18-30 years). The mean serum GFAP concentrations were 86.37 ng/mL in the patients and 38.07 ng/mL in the controls (P < 0.05). The mean serum S100B concentrations were 428.37 pg/mL in the patients and 103.44 pg/mL in the controls (P < 0.05). Eight (12.7%) patients died in the hospital; of those, the mean GCS score was 4.6, and the mean GFAP and S100B levels were 127.8 ng/mL and 860.6 pg/mL, respectively., Conclusion: The GFAP and S100B concentrations were significantly higher in patients with traumatic or nontraumatic brain injury than in healthy individuals, indicating that serum levels of these biomarkers may provide an alternative to computed tomography for the diagnosis of brain injury., Competing Interests: There are no conflicts of interest

Objective: To determine if serum S100B increases similarly as a result of playing American football compared to exercise alone., Methods: Serum S100B was measured in division III collegiate football players before and after every home game during a single football season. Serum S100B was also measured before and after subjects walked on a treadmill for 30 minutes at a leisurely pace, ran on a treadmill while wearing and not wearing a football helmet at 6 mph for 8 minutes, and performed low-, moderate-, or high-intensity resistance exercise., Results: Serum S100B increased significantly (P < 0.05) when subjects played in a football game, ran on a treadmill, or performed moderate-intensity resistance exercise. Pre-game serum S100B did not accumulate throughout the football season in any of the players (P > 0.05). The increase in serum S100B during football games was moderately and significantly correlated with both the number of hits (R 2  = 0.407) and the number of plays (R 2  = 0.484) that each player experienced (P < 0.001). Post-game serum S100B was greater in football players who played more than 50 plays compared to those players who played <50 plays, subjects who exercised on a treadmill, or subjects performing resistance exercise (P < 0.05)., Conclusion: It is unclear if the higher S100B concentration in football players playing at least 50 plays was caused by exercise or hits. Therefore, if serum S100B is to be used as a biomarker of impacts, and possible brain injury in sport, exercise time and intensity should be taken into account as confounding variables., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Mesial temporal lobe epilepsy (MTLE) associated with hippocampal sclerosis (HS) is the most common form of partial epilepsy. The aim of the present study is to highlight possible and suitable biomarkers that can help in the diagnosis and prognosis of this intractable form of epilepsy. The study was carried out on 30 epileptic patients of both sexes with complex partial seizures, having an age ranging from 4 to 30 years and were selected from the outpatient epilepsy clinic at the Kasr El-Aini Hospital in Cairo, Egypt. Thirty healthy children and young adults, age- and sex-matched to the patients, were included in the study as controls. Patients with epilepsy and healthy controls were subjected to a set of laboratory analyses including S100 calcium-binding protein B (S100B), matrix metallopeptidase 9 (MMP9), C-reactive protein (CRP), and prolactin (PRL), in addition to neurophysiological, radiological, and psychometric assessments, on the basis of the recent evidence of the field. The results of this study showed a marked increase in the investigated biomarkers in patients with epilepsy compared to controls. The performance of the epileptic patients in psychometric assessments was below the average threshold, with the MRI analysis showing specific findings of mesial temporal sclerosis (MTS) and EEG showing anterior temporal spikes. A significant negative correlation was found between MMP9 and psychometric test. On the other hand, a significant positive correlation was observed between seizure severity and the indicated biomarker. The present study suggests that S100B and MMP9 could be used as biomarkers for neuronal injury and helps in the prognosis of MTLE.

The present study examined whether serum biomarkers can predict the prognosis of childhood epilepsy, including seizure frequency, electroencephalographic (EEG) changes, and cognitive impairment. We measured serum concentrations of high mobility group protein B1 (HMGB1), interleukin-1β (IL-1β), S100 calcium-binding protein B (S-100B), glial fibrillary acidic protein (GFAP), and α1-antichymotrypsin (AACT) in 180 children with new-onset epilepsy and 40 healthy children. Cognitive evaluations were performed 18 months after the initial seizure episodes at diagnosis (ie, baseline visit). The relationship between serum biomarkers and epilepsy prognosis was investigated using Pearson correlation coefficients, logistic regression analyses, and receiver operating characteristic curves. Sixty-seven patients had generalized tonic-clonic seizures, 92 had focal motor seizures, and 21 had epileptic spasms. Serum concentrations of HMGB1, IL-1β, S-100B, and GFAP were significantly higher in the epilepsy group within 24 hours of a seizure episode than in the control group. Furthermore, HMGB1 and IL-1β were significant predictors of epilepsy prognosis. Receiver operating characteristic curve analysis revealed that HMGB1 could more accurately predict seizure frequency than IL-1β; when the serum concentration of HMGB1 was >9.625 ng/mL, there was 80.6% sensitivity and 92.5% specificity for predicting seizure frequency reduction. In conclusion, HMGB1 and IL-1β have a predictive value for epilepsy prognosis in children.

Purpose: The purpose of this study is to investigate the relationship between premature brain injury and multiple biomarkers in cord blood and amniotic fluid, identify potential biomarkers for early monitoring of premature brain injury., Methods: One hundred and thirty cases of singleton premature infants with gestational age less than 34 weeks were evaluated. Based on brain imaging examination, all cases were divided into the brain injury group and the no brain injury group. Eleven biomarkers in cord blood and amniotic fluid were measured., Results: Levels of interleukin-1β (IL-1β), IL-6, IL-8, tumor necrosis factor-α (TNF-α), granulocyte colony-stimulating factor (G-CSF), monocyte chemotactic protein-1 (MCP-1), soluble intercellular adhesion molecule-1 (sICAM-1), S100B, and activin A were higher in the brain injury group than those in the no brain injury group, in addition to S100B in amniotic fluid (p > .05), the differences were all statistically significant (p < .05). In the value of predicting brain injury, S100B had the highest sensitivity in cord blood, IL-1β had the highest sensitivity in amniotic fluid, and activin A owned the highest specificity both in cord blood and amniotic fluid. Levels of IL-4 and IL-17A were too low and had no predictive value to brain injury., Conclusions: A variety of biomarkers in umbilical blood and amniotic fluid can predict preterm brain injury.

Objectives: To critically review current knowledge on the positive and negative predictive value of blood biomarkers for concussion; to illustrate the clinical and biological contexts that help evaluate the use of these markers in sport-related traumatic brain injuries (TBIs)., Methods: This systematic review was performed in accordance with PRISMA guidelines. We reviewed the measurement, clinical utility, endpoint, and biological significance of blood biomarkers in concussion., Results: A total of 4352 publications were identified. Twenty-six articles relating to blood biomarkers were included in the review. Four common blood biomarkers, namely S100B, tau, neuron-specific enolase (NSE), and glial fibrillary acidic protein (GFAP), were examined. Overall, the studies showed S100B measurement and use, either acutely or at several time points, can distinguish injured from noninjured patients with an uncertain degree of utility in predicting mortality. At present, S100B has largely become an acceptable biomarker of TBI; however, studies have begun to highlight the need to incorporate clinical symptoms instead of S100B concentration in isolation on the basis of inconsistent results and lack of specificity across published studies. Further research is needed to evaluate and validate the use of tau, NSE, and GFAP as a diagnostic aid in the management of concussion and TBI., Conclusions: At present, blood biomarkers have only a limited role in the evaluation and management of concussion. Although several biomarkers of brain injury have been identified, continued research is required. S100B holds promise as the most clinically useful diagnostic biomarker. Blood biomarkers, in combination with other clinical data, such as head computed tomography, would maximize the diagnostic accuracy. The methodological limitations evident in blood biomarker research results in the need for the clinical utility of blood biomarker use in concussion to be further explored.

Purpose: S100B, a cytokine produced by astrocytes, has been studied as a biomarker of glial and neuronal damage in epilepsy. The present study investigated the reliability of serum S100B as a biomarker and the effect of carbamazepine and oxcarbazepine on serum S100B in patients with focal seizure., Methods: The present randomized, open-label, active-controlled, parallel design clinical trial (NCT02705768) conducted on 60 patients with focal seizure. After recruitment, clinical evaluations were performed including Chalfont-National Hospital seizure severity scale (NHS3), Quality of Life in Epilepsy Inventory (QOLIE-31) and serum S100B was estimated. Thirty healthy individuals were recruited for evaluation of serum S100B at baseline only. After randomization, the study groups received either tablet oxcarbazepine or tablet carbamazepine. At follow-up after 2 weeks, clinical status was checked and at 4 weeks, NHS3 and QOLIE-31 were scored along with serum S100B level estimation., Results: Serum S100B level in patients with focal seizure increased significantly in comparison to healthy volunteers. The decrease in serum S100B was significantly higher with carbamazepine group (0.004; 95% CI 0.001-0.006; p = 0.01) over oxcarbazepine group. In logistic regression analysis, there was an increase in the log odds of 0.17 for focal seizure positivity against healthy controls if S100B level increases by 1 pg and area under curve obtained by ROC analysis was 0.96 (p < 0.001)., Conclusion: Serum S100B increases in the patients with focal seizure and therapy with carbamazepine can decrease serum S100B level significantly over oxcarbazepine. Serum S100B can be used as a prognostic biomarker in a focal seizure.

Background: The aim of this study was to investigate serum S100B and brain-derived neurotrophic factor (BDNF) in systemic lupus erythematous (SLE) patients, with and without neuropsychiatric (NP) manifestation activity., Methods: We assessed 47 SLE patients and 20 selected healthy individuals. Disease activity was assessed according to the SLE disease activity index (SLEDAI). Serum BDNF and S100B were measured by enzyme-linked immunosorbent assay., Results: Serum S100B protein was significantly higher in SLE patients. BDNF levels were significantly decreased in active SLE, when compared with inactive SLE, but not when compared with controls. S100B was clearly higher in the NPSLE group, when compared with the non-NPSLE or control groups. Receiver operating characteristic analysis of S100B revealed an area under the curve of 0.706 that discriminated NPSLE patients with peripheral polyneuropathy., Conclusions: Our findings reinforce the use of serum S100B as a biomarker in SLE, particularly for NPSLE. Moreover, we found a strong association between serum S100B and peripheral neuropathy, indicating a specific utility for this biomarker in SLE that warrants clinical investigation.

Background: This study's primary objective was to validate the routine use of S100B via a prospective study. The aim was a reduction of cranial computed tomography (CCT) scans by 30%. The secondary goal was to investigate the influence of age and associated risk factors on the reduction of CCT., Methods: S100B (sampling within 3 h postinjury) was used for patients with mild traumatic brain injury (mTBIs) presenting a medium risk of complications and requiring a CCT scan. Patients with negative S100B (S100B-) were discharged without a CCT scan., Results: Of the 1449 patients included in this study, 468 (32.3%) had S100B- with a sensitivity of 96.4% (95% CI: 87.5%-99.6%), a specificity of 33.4% (95% CI: 31%-36%) and a negative predictive value of 99.6% (95% CI: 98.5%-99.9%). No significant difference in serum levels or the S100B+ rate was observed if patients had retrograde amnesia (0.16 μg/L; 63.8%), loss of consciousness (0.13; 63.6%) or antiplatelet therapy (0.20; 77.9%). Significant differences were found between the S100B concentrations and S100B positivity rates in patients >65 years old and all the groups with patients <55 years old (18-25, 26-35, 36-45 and 46-55). From 18 to 65 years old (n=874), the specificity is 39.3% (95% CI: 36%-42.6%) compared to 18.7% (95% CI: 15.3%-22.3%) for patients >65 years old (n=504)., Conclusions: The clinical use of S100B in mTBI management reduces the use of CCTs by approximately one-third; furthermore, the percentage of CCTs reduction is influenced by the age of the patient.

Objective: To analyze serum levels of S100 calcium-binding protein B (S100B), neuron-specific enolase (NSE), and interleukin (IL)-6 in pediatric patients with traumatic brain injury (TBI) and to assess their relationship with clinical outcome., Methods: To measure biomarkers, peripheral venous blood was collected within 6 hours and 1 week after TBI. Initial Glasgow Coma Scale (GCS) scores and Glasgow Outcome Scale scores 6 months after the trauma were used to evaluate clinical outcome., Results: Median serum levels of S100B (178.12 pg/mL), NSE (16.54 ng/mL), and IL-6 (15.48 pg/mL) at admission decreased significantly 1 week after TBI to 40.86 pg/mL, 5.85 ng/mL, and 8.63 pg/mL. In the group with poor GCS scores, serum S100B and NSE levels both at admission and 1 week after TBI were significantly higher than levels in the group with good GCS scores. Serum S100B and NSE levels 1 week after injury in patients with unfavorable 6-month outcomes were significantly higher than levels 1 week after injury in patients with favorable outcomes., Conclusions: Serum levels of S100B, NSE, and IL-6 decreased 1 week after injury. Serum levels of S100B and NSE at admission were related to initial GCS scores, and these levels 1 week after TBI were related to 6-month Glasgow Outcome Scale scores. Thus, serial measurements of serum S100B and NSE, but not IL-6, may help assess brain damage and clinical outcome of pediatric patients with TBI., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: S100B is a calcium-binding protein located in glial cells; it is regarded as a potential biomarker in affective disorders., Aim: To review the literature investigating the role of S100B in patients with affective disorders., Method: A systematic review of original English language studies investigating S100B in serum, cerebrospinal fluid, plasma and lymphocytes, in patients with affective disorders, was conducted. The literature search was conducted within the PubMed database. Effect sizes were calculated to adjust for systematic measurement effects., Results: Twenty studies were included, with a total of 1292 participants. Of these, 398 patients had or have had depressive disorder, 301 patients had bipolar disorder and 593 were healthy controls. S100B levels in serum were consistently elevated in studies with statistically significant results which investigated acute affective episodes (comprising major depressive episode in major depressive disorder, and both manic and depressive episodes in patients with bipolar disorder), in comparison to healthy controls. There were few studies assessing S100B levels in cerebrospinal fluid, plasma or lymphocytes, and these had inconsistent results., Conclusion: The results indicated that elevated S100B levels might be associated with mood episodes in affective disorders. However, the role of S100B, and its possible impact in affective disorders, requires further investigation and at the present S100B does not have a role as clinically biomarker in affective disorder. Future longitudinal multicentre studies with larger transdiagnostic real life patient cohorts are warranted.

To investigate the role of S100B, oxidative stress and the apoptosis signaling pathways in the sevoflurane induced neuroprotective effect on stroke. The brain injury, molecular and cellular damage, and functional recovery were investigated upon ischemic brain injury followed by sevoflurane treatment. Longa rodent stroke scales was used to quantify neurological deficits. TTC staining was used to measure infarct volume of brain tissue. Absolute brain water content was measured by wet/dry weight method. The neuronal morphological change was assessed by H and E staining. The spatial learning and memory ability were measured by water maze test. Serum proteins including S100B, GSH-PX, SOD, Bcl-2, Bax, Caspase-3 were measured by ELISA. The level of NOS and NO in serum was determined by colorimetric method. Compared with control, the serum proteins including S100B, Bax, NO, Caspase-3, and NOS activity in cerebral infarction rats increased significantly while SOD, GSH-PX, and Bcl-2 decreased significantly. Diabetic mellitus complicated with cerebral infarction rats showed more dramatic increase for S100B, Bax, NO, Caspase-3, and NOS activity and dramatic decrease for SOD, GSH-PX, and Bcl-2. Interestingly, sevoflurane reduced the changes significantly. The S100B level positively correlated with brain damage, NO, Bax, caspase-3, and NOS activity but negatively correlated with SOD, Bax, and GSH-PX. Brain damage in sevoflurane groups decreased while behavior outcomes including Longa neurologic score, learning, and memory increased significantly. The neuroprotective effect of sevoflurane is associated with defense mechanisms against free radical-induced oxidative stress and inhibition of apoptosis. S100B protein correlated with oxidative stress and the apoptosis signaling pathways.

Introduction: The risk of air microembolism during cardiopulmonary bypass (CPB) is high and influences the postoperative outcome, especially in elderly patients. The use of carbon dioxide (CO 2 ) atmosphere during cardiac surgery may reduce the risk of cerebral air microembolism. The aim of our study was to assess the influence of CO 2 field flooding on microembolism-induced brain damage assessed by the level of S100ß protein, regarded as a marker of brain damage., Materials and Methods: A group of 100 patients undergoing planned mitral valve operation through median sternotomy using standard CPB was recruited for the study. Echocardiography was performed prior to and after the CPB. CO 2 insufflation at 6 L/minute was conducted in the study group. Blood samples for S100ß protein analysis were collected after induction of anesthesia, 2 hours after aorta de-clamping, and 24 hours after operation., Results: The S100ß level in blood plasma did not differ significantly between the study and the control group (0.13±0.08 µg/L, 1.12±0.59 µg/L, and 0.26±0.23 µg/L and 0.18±0.19 µg/L, 1.31±0.62 µg/L, and 0.23±0.12 µg/L, P =0.7, 0.14, and 0.78). The mean increase of the S100ß concentration was 13% lower in the group with CO 2 protection than in the control group (0.988 µg/L vs 1.125 µg/L), although statistically insignificant. Tricuspid valve annuloplasties (TVAs) had significant impact on the increase in S100ß concentration in the treatment group after 24 hours (TVA [-] 0.21±0.09 vs TVA [+] 0.42±0.42, P =0.05). In patients <60 years, there were significant differences in the S100ß level 2 and 24 hours after the procedure (1.59±0.682 µg/L vs 1.223±0.571 µg/L, P =0.048, and 0.363±0.318 µg/L vs 0.229±0.105 µg/L, P =0.036) as compared with younger patients., Conclusion: The increase in S100ß concentration was lower in the group with CO 2 protection than in the control group. Age and an addition of TVA significantly influenced the level of S100ß concentration in the tests performed 2 hours after aortic clamp release., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Background: Kudiezi injection is a traditional Chinese medicine for acute cerebral infarction, but the exact mechanisms are poorly understood., Objective: To investigate the mechanisms of Kudiezi injection on the inflammatory response in the treatment of acute cerebral infarction., Methods: This was a prospective study of patients with acute cerebral infarction within 48 h of onset and treated between July 2012 and July 2016 at three hospitals in China. The patients were randomized to routine treatments (control group) versus routine treatments and Kudiezi injection (Kudiezi group). The National Institutes of Health Stroke Score was assessed on days 1, 3, 5, 7, and 14. The patients were tested for serum levels of pro- and anti-inflammatory cytokines (S100 calcium-binding protein B, neuron-specific enolase, interleukin-6, interleukin-10, interleukin-18, and matrix metaloproteinase-9; by enzyme-linked immunosorbent assay) immediately after admission and on days 3, 5, and 14., Results: Stroke scores were improved in both groups from days 1 to 14. On days 5 and 7, stroke scores in the Kudiezi group were lower than in the control group ( P < 0.05). Compared with controls, the Kudiezi group had lower serum S100 calcium-binding protein B on day 14; higher interleukin-6 and interleukin-10 on day 3; lower interleukin-6 and interleukin-18 on day 5; and lower interleukin-18 and matrix metaloproteinase-9 on day 14., Conclusion: Kudiezi injection could lead to early reduction of interleukin-6, interleukin-18, matrix metaloproteinase-9, neuron-specific enolase, and S100 calcium-binding protein B levels and increases of interleukin-10 levels in patients with acute ischemic stroke. This trial is registered with ClinicalTrials.gov NCT01636154.

Elevated serum and cerebrospinal fluid concentrations of S100β, a protein predominantly found in glia, are associated with intracranial injury and neurodegeneration, although concentrations are also influenced by several other factors. The longitudinal association between serum S100β concentrations and brain health in nonpathological aging is unknown. In a large group (baseline N = 593; longitudinal N = 414) of community-dwelling older adults at ages 73 and 76 years, we examined cross-sectional and parallel longitudinal changes between serum S100β and brain MRI parameters: white matter hyperintensities, perivascular space visibility, white matter fractional anisotropy and mean diffusivity (MD), global atrophy, and gray matter volume. Using bivariate change score structural equation models, correcting for age, sex, diabetes, and hypertension, higher S100β was cross-sectionally associated with poorer general fractional anisotropy (r = -0.150, p = 0.001), which was strongest in the anterior thalamic (r = -0.155, p < 0.001) and cingulum bundles (r = -0.111, p = 0.005), and survived false discovery rate correction. Longitudinally, there were no significant associations between changes in brain imaging parameters and S100β after false discovery rate correction. These data provide some weak evidence that S100β may be an informative biomarker of brain white matter aging., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To explore the effect of ginkgo biloba extract (EGb) as an adjunctive treatment of elderly patients with depression and the effect on the expression of serum S100B., Methods: 136 elderly patients with depression were divided into EGb +  citalopram (Cit) group and Cit group equally. Efficacy was evaluated by Hamilton Depression Rating Scale (HAMD). Wisconsin Card Classification Test (WCST) was used to evaluate cognitive function. Serum S100B expression was measured with ELISA. The relationship of S100B with HAMD, Hamilton Anxiety Scale (HAMA) score, and WCST results was evaluated subsequently., Results: The time of onset of efficacy was significantly shorter in EGb + Cit group. There were significant differences in HAMD and HAMA scores after treatment than before treatment between groups (all P < .05). After treatment, total number of WCST test, the number of continuous errors and non-persistent errors in both groups were less than those before treatment. The correct number and classifications number were increased than before treatment. In EGb + Cit group, correct numbers and classifications were increased, and the number of persistent errors was decreased. After treatment, S100B level was decreased, and S100B levels change in EGb + Cit group was greater than in Cit group. Serum S100B level was positively correlated with HAMD and HAMA scores before treatment and positively correlated with persistent errors number in WCST., Conclusion: EGb, as an adjunctive treatment, can effectively improve depressive symptoms and reduce expression of serum S100B, which is a marker of brain injury, suggesting that EGb restores neurologic function during the treatment of depression in elderly patients and S100B participates in the therapeutic mechanism. EGb combined with depressive drugs plays synergistic role, and the time of onset of efficacy is faster than single antidepressants.

Background: While S-100B protein and Neuron-Specific Enolase (NSE) dosages have been extensively investigated for neurological prognostication after cardiac arrest (CA), there is no data about their ability to detect a cerebrovascular cause of CA. We assessed the utility of plasma S-100B protein and NSE measurements for early diagnosis of primary neurological cause in resuscitated CA patients., Patients and Methods: Case control study based on two prospectively acquired CA databases. Patients with a primary cerebrovascular etiology were compared with randomly selected CA of non-neurological cause. S-100B protein and NSE were measured at ICU admission in all patients., Results: CA was due to a cerebrovascular etiology in 18 patients (subarachnoid hemorrhage, n = 15; ischemic stroke, n = 3), with an ICU mortality of 100%. Comparative group was constituted with 66 patients (cardiac etiology n = 45, respiratory etiology n = 21), with an ICU mortality of 71%. Admission S-100B protein concentration was 2.0 [0.63-7.15] μg/L in the cerebrovascular group and 0.45 [0.24-1.95] in the non-cerebrovascular group (p < 0.001). In contrast, NSE concentration was similar in cerebrovascular and non-cerebrovascular etiologies (35 [25-103] μg/L vs. 27 [19-47] respectively, p = 0.16). Area under ROC curves for S-100B protein and NSE to predict cerebrovascular cause of CA was 0.75 [95% CI: 0.64-0.87] and 0.61 [95% CI: 0.45-0.76], respectively., Conclusions: Even if S-100B protein dosage performs slightly better than NSE, early dosages of these biomarkers are poorly predictive of a cerebrovascular etiology of CA. Our results suggest that early measurement of brain biomarkers should not be recommended to tailor the imaging strategy employed to investigate the CA cause., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Mercury is a heavy metal responsible for human intoxication worldwide and especially in the Amazon, where both natural and anthropogenic sources are responsible for exposure in riverine populations. Methylmercury is the most toxic specie of mercury with recognized neurotoxicity due to its affinity for the central nervous system. S100B protein is a well-established biomarker of brain damage and it was recently associated with mercury-related neurotoxicity. Accurate measurement is especially challenging in isolated/remote populations due to the difficulty of adequate sample conservation, therefore here we use S100B mRNA levels in blood as a way to assay mercury neurotoxicity. We hypothesized that individuals from chronically exposed populations showing mercury levels above the limit of 10 μg/g in hair would present increased levels of S100B mRNA, likely due to early brain damage. A total of 224 riverine individuals were evaluated for anthropometric data (age, body mass index), self-reported symptoms of mercury intoxication, c-reactive protein in blood, and mercury speciation in hair. Approximately 20% of participants showed mercury levels above the limit, and prevalence for most symptoms was not different between individuals exposed to high or low mercury levels. Rigorous exclusion criteria were applied to avoid confounding factors and S100B mRNA in blood was tested by RT-qPCR. Participants with ≥10 μg/g of mercury had S100B mRNA levels over two times higher than that of individuals with lower exposure. A significant correlation was also detected between mercury content in hair and S100B mRNA levels in blood, supporting the use of the latter as a possible candidate to predict mercury-induced neurotoxicity. This is the first report of an association between S100B mRNA and mercury exposure in humans. The combination of both exposure and intoxication biomarkers could provide additional support for the screening and early identification of high-risk individuals in isolated populations and subsequent referral to specialized centers., (Copyright © 2018 Elsevier B.V. All rights reserved.)

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.)