S100B Concentrations Research Articles

Neuroprotective effect of remote ischemic preconditioning in patients undergoing cardiac surgery: A randomized controlled trial.

BackgroundThe neuroprotective effect of remote ischemic preconditioning (RIPC) in patients undergoing elective cardiopulmonary bypass (CPB)-assisted coronary artery bypass graft (CABG) or valvular cardiac surgery remains unclear.MethodsA randomized, double-blind, placebo-controlled superior clinical trial was conducted in patients undergoing elective on-pump coronary artery bypass surgery or valve surgery. Before anesthesia induction, patients were randomly assigned to RIPC (three 5-min cycles of inflation and deflation of blood pressure cuff on the upper limb) or the control group. The primary endpoint was the changes in S-100 calcium-binding protein β (S100-β) levels at 6 h postoperatively. Secondary endpoints included changes in Neuron-specific enolase (NSE), Mini-mental State Examination (MMSE), and Montreal Cognitive Assessment (MoCA) levels.ResultsA total of 120 patients [mean age, 48.7 years; 36 women (34.3%)] were randomized at three cardiac surgery centers in China. One hundred and five patients were included in the modified intent-to-treat analysis (52 in the RIPC group and 53 in the control group). The primary result demonstrated that at 6 h after surgery, S100-β levels were lower in the RIPC group than in the control group (50.75; 95% confidence interval, 67.08 to 64.40 pg/ml vs. 70.48; 95% CI, 56.84 to 84.10 pg/ml, P = 0.036). Compared to the control group, the concentrations of S100-β at 24 h and 72 h and the concentration of NSE at 6 h, 24 h, and 72 h postoperatively were significantly lower in the RIPC group. However, neither the MMSE nor the MoCA revealed significant between-group differences in postoperative cognitive performance at 7 days, 3 months, and 6 months after surgery.ConclusionIn patients undergoing CPB-assisted cardiac surgery, RIPC attenuated brain damage as indicated with the decreased release of brain damage biomarker S100-β and NSE.Clinical trial registration[ClinicalTrials.gov], identifier [NCT01231789].

Early predictors of abnormal MRI patterns in asphyxiated infants: S100B protein urine levels.

The early detection and stratification of asphyxiated infants at higher risk for impaired neurodevelopment is challenging. S100B protein is a well-established biomarker of brain damage, but lacks conclusive validation according to the "gold standard" methodology for hypoxic-ischemic encephalopathy (HIE) prognostication, i.e. brain MRI. The aim of the present study was to investigate the predictive role of urinary S100B concentrations, assessed in a cohort of HIE infants receiving therapeutic hypothermia (TH), compared to brain MRI. Assessment of urine S100B concentrations was performed by immunoluminometric assay at first void and at 4, 8, 12, 16, 20, 24, 48, 72, 96, 108 and 120-h after birth. Neurologic evaluation, routine laboratory parameters, amplitude-integrated electroencephalography, and cerebral ultrasound were performed according to standard protocols. Brain MRI was performed at 7-10days of life. Overall, 74 HIE neonates receiving TH were included in the study. S100B correlated, already at first void, with the MRI patterns with higher concentrations in infants with the most severe MRI lesions. High S100B urine levels soon after birth constitute trustable predictors of brain injury as confirmed by MRI. Results support the reliability of S100B in clinical daily practice and open the way to its inclusion in the panel of parameters used for the selection of cases suitable for TH treatment.

Correlation of BDNF, VEGF, TNF‐α, and S100B with cognitive impairments in chronic, medicated schizophrenia patients

Cognitive impairment is a prominent cause of disability in schizophrenia. Although antipsychotic drugs can rescue the psychotic symptoms, the cognitive impairments persist, with no treatment available. Alterations of BDNF, VEGF, TNF‐α, and S100B have been linked to cognitive impairment in several neurological disorders. However, it remains unclear whether their levels are correlated with the cognitive functions of schizophrenia patients. Forty‐one chronic, medicated schizophrenia patients were included in this study. Enzyme‐linked, immunosorbent assays were used to measure the serum concentrations of BDNF, VEGF, TNF‐α, and S100B. Associations between serum protein levels and various domains of the cognitive functions of the schizophrenia patients were observed. We found significant, positive correlations between serum BDNF and the processing speed and attention levels of the patients. Serum VEGF was also positively correlated with their memory and learning functions. In contrast, serum S100B and TNF‐α were negatively correlated with the processing speed and attention of the schizophrenia patients. The findings warrant further investigation of these molecules as potential prognostic markers or treatment targets for cognitive impairment in schizophrenia patients.

Inflammatory Markers Combined With Metalloproteinase-9, Neopterin, and S100B Concentrations May Indicate the Pathogenesis of Central Nervous System Diseases in Children.

The identification of central nervous system inflammation etiology leads to adjusted therapy. We analyzed the potential inflammatory and neuro-axonal damage markers in children. Our target was to correlate the findings with a disease's course or a sequalae risk and assess their clinical usefulness. The study included 96 children with symptoms of central nervous system inflammation who underwent diagnostics. The research group involved 24 children with autoimmune disorders and 31 with neuroinfection. The control group included patients with both etiologies excluded. We analyzed the results of routine laboratory tests together with chosen serum (neopterin, interleukin [IL]-1β, IL-6) and CSF (metalloproteinase [MMP]-9, S100B protein) markers. In the whole cohort, CSF MMP-9 correlated with CSF cytosis and serum IL-6 and CRP. In the undivided neuroinflammatory group, CSF S100B correlated with serum IL-6 and IgM concentrations. CSF cytosis was associated with CSF MMP-9 and serum neopterin levels. Among the infective patients, IL-6 was linked with increased CSF MMP-9. We conclude that astroglial protein S100B, neopterin, and cytokine concentrations may enable predicting long-term consequences, whereas CSF MMP-9 concentration may reflect the actual central nervous system injury regardless of etiology.

Brain damage markers neuron-specific enolase (NSE) and S100B in serum in children with Lyme neuroborreliosis—detection and evaluation as prognostic biomarkers for clinical outcome

Lyme borreliosis (LB) is the most common tick-borne infection in Europe, with Lyme neuroborreliosis (LNB) its second most frequent clinical manifestation. Prognostic factors for clinical outcomes in LNB have not been identified. Elevated serum levels of the brain damage markers neuron-specific enolase (NSE) and S100 calcium-binding protein B (S100B) have been associated with poor clinical outcomes in other disorders of the central nervous system. The aim of this study is to assess NSE and S100B in serum as prognostic biomarkers for clinical outcomes in paediatric LNB patients. Children evaluated for LNB (n = 121) in Sweden were prospectively included during 2010–2014, serum samples were collected on admission, and all children underwent a 2-month follow-up. Patients with pleocytosis and anti-Borrelia antibodies in cerebrospinal fluid (CSF) were classified as having LNB (n = 61). Controls were age- and gender-matched non-LNB patients (n = 60). NSE was elevated in 38/61 (62%) LNB patients and in 31/60 (52%) controls. S100B was elevated in 3/60 (5%) LNB patients and 0/59 (0%) controls. NSE and S100B concentrations did not differ significantly when comparing LNB patients with controls. No differences were found in the concentrations when comparing the clinical recovery of LNB patients at the 2-month follow-up. NSE was detectable in the majority of LNB patients and controls, whereas S100B was detectable in only a few LNB patients and no controls. NSE and S100B in serum cannot be recommended as prognostic biomarkers for clinical outcomes in children with LNB.

Prognostic properties of the association between the S-100B protein levels and the mean cerebral blood flow velocity in patients diagnosed with severe traumatic brain injury.

Craniocerebral injury (CBI) is tissue damage caused by a sudden mechanical force. CBI can result in neurological, neuropsychological and psychiatric dysfunctions. Currently, the severity of CBI is assessed using the Glasgow Coma Scale, brain perfusion pressure measurements, transcranial Doppler tests and biochemical markers. This study aimed to determine the applicability of the S-100B protein levels and the time-averaged mean maximum cerebral blood flow velocity (Vmean) as a means of predicting the treatment outcomes of CBI in the first 4 days of hospitalization. The results validated the standard reference ranges previously proposed for the concentration of S-100B (0.05-0.23 µg/l) and the mean of cerebral blood flow velocity (30.9 to 74.1 cm/sec). The following stratification scheme was used to predict the success of treatment: Patients with a Glasgow Outcome Scale (GOS) score ≥4 or GOS <4 were stratified into ‘favorable’ and ‘unfavorable’ groups, respectively. The favorable group showed relatively constant levels of the S-100B protein close to the normal range and exhibited an increase in Vmean, but this was still within the normal range. The unfavorable group exhibited a high level of S-100B protein and increased Vmean outside of the normal ranges. The changes in the levels of S-100B in the unfavorable and favorable groups were -0.03 and -0.006 mg/l/h, respectively. Furthermore, the rate of decrease in the Vmean value in the unfavorable and favorable groups were -0.26 and -0.18 cm/sec/h, respectively. This study showed that constant levels of S-100B protein, even slightly above the normal range, associated with an increase in Vmean was indicative of a positive therapeutic outcome. However, additional research is required to obtain the appropriate statistical strength required for clinical practice.

Pulmonary vein isolation by pulsed-field ablation induces smaller neurocardiac damage than cryoballoon ablation

Abstract Funding Acknowledgements Type of funding sources: Private company. Main funding source(s): FARAPULSE, Inc. Introduction Thermal energy sources damage the entire atrial tissue during pulmonary vein isolation (PVI) including cardiac nerves and ganglia. This induces a postinterventional increase in heart rate. Pulsed-field ablation (PFA), a new non-thermal energy source for PVI, primarily damages cardiomyocytes by electroporation. Whether use of PFA reduces damage to cardiac nerves and ganglia and influences postinterventional increase of heart rate is not known. Purpose We compared the acute effects of PFA with a pentaspline catheter and cryoballoon ablation (CBA) on secretion of circulating biomolecules reflecting cardiomyocyte and neuronal injury and postinterventional increase in heart rate to estimate damage to the cardiac autonomic nervous system and autonomic dysfunction after PVI. Methods Blood samples were taken before and after PVI in consecutive patients undergoing PFA and CBA. All patients participated in the TRUST registry. Serum concentrations of high-sensitive Troponin I (hsTropI, Immunoassay) and S100b (ELISA), a surrogate marker for neuronal injury, were quantified in blood samples taken prior to PVI and directly after PVI. Pre- and postinterventional heart rates were measured in ECGs and Holter-ECGs. Results Fifty-six patients underwent PVI, either by PFA (n=28, age 63 [54; 75] y, 64% males, 57% persistent AF) or CBA (n=28, age 71 [62; 78] y, 61% males, 54% persistent AF). All 112 blood samples were analyzable. Acute success of PVI was 100% in both groups without major complications, especially, no TIA and no stroke. After CBA, one patient suffered from phrenic palsy, which reversed after 3 months. HsTropI increased 3.3-fold more after PFA compared to CBA (625±138 vs. 185±42 pg/ml; p=0.004) suggesting more damage to cardiomyocytyes. S100b increased 2.9-fold less after PFA compared to CBA (21.1±3.7 vs. 61.2±8.1 pg/ml; p&amp;lt;0.001). The ratio of ∆S100b/∆hsTropI was five-fold smaller after PFA compared to CBA (0.19±0.1 vs. 0.98±0.3; p=0.007), suggesting a lower neurocardiac injury in comparison to lesion size. Concomitantly, increase in heart rate at the postinterventional day was smaller in PFA (-0.2±3.0 bpm; n=45) than in CBA (+6.1±2.7 bpm, n=15; p=0.024). Conclusion This study in patients validates the experimental concept that PFA-based AF ablation leads to more specific damage to cardiomyocytes than to cardiac nerves and ganglia, reflected by lower S100B concentrations and no post-interventional heart rate increase compared to CBA.

Predictive effect of Bayes discrimination in the level of serum protein factors and cognitive dysfunction in schizophrenia

Finding molecular biomarkers that can be related to the degree of cognitive dysfunction in schizophrenia remains a challenge. The levels of 6 Serum Protein Factors (NGF, BDNF, IL-6, TNF-α, S100β, GFAP) in peripheral blood of patients with schizophrenia were measured. The cognitive function of patients with schizophrenia was assessed by MATRICS Consensus Cognitive Battery (MCCB), a systematic assessment tool of international gold standard for cognitive function assessment of schizophrenia. To explore the correlation between these 6 biomarkers and the degree of cognitive dysfunction in schizophrenia,78 schizophrenic patients and 71 healthy controls were included in the study. The serum concentrations of BDNF and GFAP were lower in the patient group, but the concentrations of IL-6, TNF-α and S100β were higher. The speed of information processing, word learning, reasoning and problem solving, visual learning T-score of the patient group were lower than the control group. Bayes discriminant function model has a high correct discriminant rate for the severity of cognitive dysfunction in schizophrenia. The level of serum protein factor and clinical symptom score of schizophrenia may forecast the degree of cognitive dysfunction, which is expected to be a potential biomarker to identify the degree of cognitive dysfunction of schizophrenia, and provide objective basis for the clinical diagnosis and treatment of patients with schizophrenia.

Microfluidic Paper-Based Blood Plasma Separation Device as a Potential Tool for Timely Detection of Protein Biomarkers.

A current challenge regarding microfluidic paper-based analytical devices (µPAD) for blood plasma separation (BPS) and electrochemical immunodetection of protein biomarkers is how to achieve a µPAD that yields enough plasma to retain the biomarker for affinity biosensing in a functionalized electrode system. This paper describes the development of a BPS µPAD to detect and quantify the S100B biomarker from peripheral whole blood. The device uses NaCl functionalized VF2 filter paper as a sample collection pad, an MF1 filter paper for plasma retention, and an optimized microfluidic channel geometry. An inverted light microscope, scanning electron microscope (SEM), and image processing software were used for visualizing BPS efficiency. A design of experiments (DOE) assessed the device’s efficacy using an S100B ELISA Kit to measure clinically relevant S100B concentrations in plasma. The BPS device obtained 50 μL of plasma from 300 μL of whole blood after 3.5 min. The statistical correlation of S100B concentrations obtained using plasma from standard centrifugation and the BPS device was 0.98. The BPS device provides a simple manufacturing protocol, short fabrication time, and is capable of S100B detection using ELISA, making one step towards the integration of technologies aimed at low-cost POC testing of clinically relevant biomarkers.

Intracellular Protein S-Nitrosylation-A Cells Response to Extracellular S100B and RAGE Receptor.

Human S100B is a small, multifunctional protein. Its activity, inside and outside cells, contributes to the biology of the brain, muscle, skin, and adipocyte tissues. Overexpression of S100B occurs in Down Syndrome, Alzheimer’s disease, Creutzfeldt–Jakob disease, schizophrenia, multiple sclerosis, brain tumors, epilepsy, melanoma, myocardial infarction, muscle disorders, and sarcopenia. Modulating the activities of S100B, related to human diseases, without disturbing its physiological functions, is vital for drug and therapy design. This work focuses on the extracellular activity of S100B and one of its receptors, the Receptor for Advanced Glycation End products (RAGE). The functional outcome of extracellular S100B, partially, depends on the activation of intracellular signaling pathways. Here, we used Biotin Switch Technique enrichment and mass-spectrometry-based proteomics to show that the appearance of the S100B protein in the extracellular milieu of the mammalian Chinese Hamster Ovary (CHO) cells, and expression of the membrane-bound RAGE receptor, lead to changes in the intracellular S-nitrosylation of, at least, more than a hundred proteins. Treatment of the wild-type CHO cells with nanomolar or micromolar concentrations of extracellular S100B modulates the sets of S-nitrosylation targets inside cells. The cellular S-nitrosome is tuned differently, depending on the presence or absence of stable RAGE receptor expression. The presented results are a proof-of-concept study, suggesting that S-nitrosylation, like other post-translational modifications, should be considered in future research, and in developing tailored therapies for S100B and RAGE receptor-related diseases.

Temporal Changes in Serum S100B Levels From Prehospital to Early In-Hospital Sampling in Patients Suffering Traumatic Brain Injury.

BackgroundThe biomarker S100B is used for the rule-out of intracranial lesions in patients with mild traumatic brain injury (TBI) and is suggested for prehospital use in Europe. Early kinetics of S100B are not exhaustively investigated in human TBI. This post hoc descriptive study of the data from the PreTBI studies aimed to characterize the early temporal changes of S100B using two-sample timepoints.Materials and MethodsTwo consecutive blood samples were taken prehospital and in-hospital after injury and assayed for S100B. The endpoint adjudication of the outcome intracranial lesion was done by the evaluation of electronic medical patient journals. The data were analyzed using descriptive statistics, scatterplots, and temporal changes estimated by the locally weighted scatterplot smoothing (LOWESS) regression line.ResultsA total of 592 adult patients with TBI were included; 566 with Glasgow Coma Scale (GCS) 14-15, 20 with GCS 9-13, and 6 with GCS 3-8. Intracranial lesions were diagnosed in 44/566 (7.4%) of patients. In 90% of patients, S100B concentrations decreased from prehospital to in-hospital sampling. The mean decrease was−0.34 μg/L. S100B concentrations seem to decline already within 60 min. Patients sampled very close to trauma and patients suffering intracranial lesions may express a slight incline before this decline. Temporal changes of S100B did not differ in patients >65 years of age, in antiplatelet/-coagulant treatment, alcohol intoxicated, or suffering extra-cranial injuries.ConclusionS100B concentrations may peak earlier than expected from previous studies of temporal changes in human TBI. Patterns of S100B stand robust to parameters stated as limiting factors to the use for early rule-out of intracranial lesions in the current guidelines. Further studies are needed to investigate the ultra-early temporal profiles of other novel TBI biomarkers to assess prehospital applicability and optimal diagnostic performance in TBI.

Reduced Concentrations of NSE, S100β, Aβ, and Proinflammatory Cytokines in Elderly Patients Receiving Ultrasound-Guided Combined Lumbar Plexus-Sciatic Nerve Block during Hip Replacement.

Objective The increase of hip fractures is related to the aging of the population, which has caused a huge medical burden in many countries. Hip replacement has been approved as a highly successful surgical intervention for the patients with hip fractures. Different anesthesia choices in the surgical intervention are associated with the prognosis of patients. This study focused on investigating the application of ultrasound-guided combined lumbar plexus-sciatic nerve block in elderly patients with hip fractures. Methods In this retrospective study, 62 elderly patients received combined spinal-epidural anesthesia and 58 elderly patients underwent ultrasound-guided combined lumbar plexus-sciatic nerve block during the surgery. Hemodynamic monitoring including pulse oxygen saturation (SpO2), heart rate and blood pressure, the assessment of pain intensity using Visual Analogue Scale (VAS), cognitive function assessment through Montreal Cognitive Assessment (MoCA) and biomarkers consisting of serum levels of neuron specific-enolase (NSE), S100 beta protein (S100-β), and amyloid beta protein (Aβ), as well as immune function by interleukin-6 (IL-6), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and high sensitivity C-reactive protein (hs-CRP) were detected in this study. Furthermore, length of hospital stay (LOS) and adverse reactions including hematoma, hypotension, nausea, and vomit were analyzed. Results The findings indicated that comparing with the patients receiving combined spinal-epidural anesthesia, those undergoing ultrasound-guided combined lumbar plexus-sciatic nerve block showed significantly lower level of heart rate, higher level of SpO2, and lower level of diastolic pressure and systolic pressure at 5 minutes and 30 minutes after anesthesia and after surgery (P < 0.05), indicated obviously lower VAS score at 12, 24, and 48 hours after surgery (P < 0.05), and revealed higher MoCA score at 12 days after surgery (P < 0.05). A significantly higher level of NSE, S100β, Aβ, IL-6, IL-1β, TNF-α, and hs-CRP was revealed in the two groups receiving different anesthesia methods at 10 days after surgery compared with that before surgery (P < 0.05). However, the patients receiving ultrasound-guided combined lumbar plexus-sciatic nerve block had obviously lower expression of NSE, S100β, Aβ, IL-6, IL-1β, TNF-α, and hs-CRP compared with the group accepting combined spinal-epidural anesthesia (P < 0.05). The two groups indicated no significant difference in incidence of hypotension and vomit, etc. (P < 0.05), but showed remarkable difference referring to total incidence of adverse reactions and LOS (P < 0.05). Conclusion The application of ultrasound-guided combined lumbar plexus-sciatic nerve block in hip replacement contributes to the stability of hemodynamics and alleviation of postoperative pain intensity. It can reduce cognitive and immune impairment of the elderly patients with hip fractures.

Serum S100B Protein Concentrations in SGA/FGR newborns.

Fetal growth restriction is associated with chronic fetal hypoxia, poor perinatal outcome and increased perinatal mortality. There are no reliable methods to detect cell damage in the central nervous system (CNS) in these patients. The findings of increased an acidic calcium-binding protein (S100B) concentration in biological fluids of infants after brain injury have supported the use of S100B as a biochemical marker of CNS damage. The purpose of the study was to assess blood S100B concentrations in small for gestational age (SGA) and appropriate for gestational age (AGA) newborns and to evaluate the usefulness of S100B for early detection of hypoxia. The investigation was carried out between November 2011 and April 2014. Serum S100B protein level was assessed in cord blood collected from newborns after birth. Medical records of mothers of neonates studied were reviewed for pregnancy induced hypertension (PIH), preeclampsia, maternal smoking during pregnancy and abnormalities in umbilical artery (UA) Doppler ultrasound examination. The study was carried out in 88 SGA neonates and 80 AGA neonates. The median value of S100B protein concentration in the SGA study group was significantly higher than in AGA controls (p < 0.001). Cord blood serum S100B concentration in SGA neonates with prenatal normal UA Doppler ultrasound findings (n = 32) did not differ from that SGA neonates with abnormal prenatal UA Doppler findings (n = 25) (p = 0.74), but was significantly higher than in AGA newborns (p < 0.001). Elevated S100B protein levels in cord blood collected from SGA newborns may be helpful in detecting infants at higher risk of postnatal neurologic disturbances at an early stage.

Cerebral Biomarkers and Blood-Brain Barrier Integrity in Preeclampsia.

Cerebral complications in preeclampsia contribute substantially to maternal mortality and morbidity. There is a lack of reliable and accessible predictors for preeclampsia-related cerebral complications. In this study, plasma from women with preeclampsia (n = 28), women with normal pregnancies (n = 28) and non-pregnant women (n = 16) was analyzed for concentrations of the cerebral biomarkers neurofilament light (NfL), tau, neuron-specific enolase (NSE) and S100B. Then, an in vitro blood–brain barrier (BBB) model, based on the human cerebral microvascular endothelial cell line (hCMEC/D3), was employed to assess the effect of plasma from the three study groups. Transendothelial electrical resistance (TEER) was used as an estimation of BBB integrity. NfL and tau are proteins expressed in axons, NSE in neurons and S100B in glial cells and are used as biomarkers for neurological injury in other diseases such as dementia, traumatic brain injury and hypoxic brain injury. Plasma concentrations of NfL, tau, NSE and S100B were all higher in women with preeclampsia compared with women with normal pregnancies (8.85 vs. 5.25 ng/L, p < 0.001; 2.90 vs. 2.40 ng/L, p < 0.05; 3.50 vs. 2.37 µg/L, p < 0.001 and 0.08 vs. 0.05 µg/L, p < 0.01, respectively). Plasma concentrations of NfL were also higher in women with preeclampsia compared with non-pregnant women (p < 0.001). Higher plasma concentrations of the cerebral biomarker NfL were associated with decreased TEER (p = 0.002) in an in vitro model of the BBB, a finding which indicates that NfL could be a promising biomarker for BBB alterations in preeclampsia.

Serum biomarkers of brain injury after uncomplicated cardiac surgery: Secondary analysis from a randomized trial.

BackgroundPostoperative cognitive dysfunction is common after cardiac surgery. Postoperative measurements of brain injury biomarkers may identify brain damage and predict cognitive dysfunction. We describe the release patterns of five brain injury markers in serum and plasma after uncomplicated cardiac surgery.MethodsSixty‐one elective cardiac surgery patients were randomized to undergo surgery with either a dextran‐based prime or a crystalloid prime. Blood samples were taken immediately before surgery, and 2 and 24 h after surgery. Concentrations of the brain injury biomarkers S100B, glial fibrillary acidic protein (GFAP), tau, neurofilament light (NfL) and neuron‐specific enolase (NSE)) and the blood–brain barrier injury marker β‐trace protein were analyzed. Concentrations of brain injury biomarkers were correlated to patients’ age, operation time, and degree of hemolysis.ResultsNo significant difference in brain injury biomarkers was observed between the prime groups. All brain injury biomarkers increased significantly after surgery (tau +456% (25th–75th percentile 327%−702%), NfL +57% (28%−87%), S100B +1145% (783%−2158%), GFAP +17% (−3%−43%), NSE +168% (106%−228%), while β‐trace protein was reduced (−11% (−17−3%). Tau, S100B, and NSE peaked at 2h, NfL and GFAP at 24 h. Postoperative concentrations of brain injury markers correlated to age, operation time, and/or hemolysis.ConclusionUncomplicated cardiac surgery with cardiopulmonary bypass is associated with an increase in serum/plasma levels of all the studied injury markers, without signs of blood–brain barrier injury. The biomarkers differ markedly in their levels of release and time course. Further investigations are required to study associations between perioperative release of biomarkers, postoperative cognitive function and clinical outcome.

TBISTAT: An open-source, wireless portable, electrochemical impedance spectroscopy capable potentiostat for the point-of-care detection of S100B in plasma samples.

Point-of-Care (POC) testing for biomarker detection demands techniques that are easy to use, readily available, low-cost, and with rapid response times. This paper describes the development of a fully open-source, modular, wireless, battery-powered, smartphone-controlled, low-cost potentiostat capable of conducting electrochemical impedance spectroscopy for the electrochemical detection of the S100B protein captured in an ANTI-S100B functionalized thin-film gold interdigitated electrode platform to support traumatic brain injury diagnosis and treatment. EIS results from the developed potentiostat were validated with a commercial benchtop potentiostat by comparing impedance magnitude and phase values along the EIS frequency range. In addition, an experimental design was performed for detecting S100B in spiked human plasma samples with S100B concentrations of clinical utility, and a calibration curve was found for quantifying S100B detection. No statistically significant differences were found between EIS results from the developed potentiostat and the commercial potentiostat. Statistically significant differences in the changes in charge transfer resistance signal between each tested S100B concentration (p < 0.05) were found, with a limit of detection of 35.73 pg/mL. The modularity of the proposed potentiostat allows easier component changes according to the application demands in power, frequency excitation ranges, wireless communication protocol, signal amplification and transduction, precision, and sampling frequency of ADC, among others, when compared to state-of-the-art open-source EIS potentiostats. In addition, the use of minimal, easy acquirable open-source hardware and software, high-level filtering, accurate ADC, Fast Fourier Transform with low spectral leakage, wireless communication, and the simple user interface provides a framework for facilitating EIS analysis and developing new affordable instrumentation for POC biosensors integrated systems.

Stress and the gut-brain axis: Cognitive performance, mood state, and biomarkers of blood-brain barrier and intestinal permeability following severe physical and psychological stress

BackgroundPhysical and psychological stress alter gut-brain axis activity, potentially causing intestinal barrier dysfunction that may, in turn, induce cognitive and mood impairments through exacerbated inflammation and blood brain barrier (BBB) permeability. These interactions are commonly studied in animals or artificial laboratory environments. However, military survival training provides an alternative and unique human model for studying the impacts of severe physical and psychological stress on the gut-brain axis in a realistic environment. PurposeTo determine changes in intestinal barrier and BBB permeability during stressful military survival training and identify relationships between those changes and markers of stress, inflammation, cognitive performance, and mood state. Materials and methodsSeventy-one male U.S. Marines (25.2 ± 2.6 years) were studied during Survival, Evasion, Resistance, and Escape (SERE) training. Measurements were conducted on day 2 of the 10-day classroom phase of training (PRE), following completion of the 7.5-day field-based simulation phase of the training (POST), and following a 27-day recovery period (REC). Fat-free mass (FFM) was measured to assess the overall physiologic impact of the training. Biomarkers of intestinal permeability (liposaccharide-binding protein [LBP]) and BBB permeability (S100 calcium-binding protein B [S100B]), stress (cortisol, dehydroepiandrosterone sulfate [DHEA-S] epinephrine, norepinephrine) and inflammation (interleukin-6 [IL-6], high-sensitivity C-reactive protein [hsCRP]) were measured in blood. Cognitive performance was assessed by psychomotor vigilance (PVT) and grammatical reasoning (GR) tests, and mood state by the Profile of Mood States (total mood disturbance; TMD), General Anxiety Disorder-7 (GAD-7), and Patient Health (PHQ-9) questionnaires. ResultsFFM, psychomotor vigilance, and LBP decreased from PRE to POST, while TMD, anxiety, and depression scores, and S100B, DHEA-S, IL-6, norepinephrine, and epinephrine concentrations all increased (all p ≤ 0.01). Increases in DHEA-S were associated with decreases in body mass (p = 0.015). Decreases in FFM were associated with decreases in LBP concentrations (p = 0.015), and both decreases in FFM and LBP were associated with increases in TMD and depression scores (all p < 0.05) but not with changes in cognitive performance. Conversely, increases in S100B concentrations were associated with decreases in psychomotor vigilance (p < 0.05) but not with changes in mood state or LBP concentrations. ConclusionsEvidence of increased intestinal permeability was not observed in this military survival training-based model of severe physical and psychological stress. However, increased BBB permeability was associated with stress and cognitive decline, while FFM loss was associated with mood disturbance, suggesting that distinct mechanisms may contribute to decrements in cognitive performance and mood state during the severe physical and psychological stress experienced during military survival training.

Neuroprotective effect of memantine on serum S100-B levels after on-pump coronary artery bypass graft surgery: A randomized clinical trial.

Background:Brain injury is one of the complications of open heart surgery. Glutamate plays a key role in this process. In this study, we evaluated the neuroprotective effect of memantine as NMDAR inhibitor in patients undergoing on-pump coronary artery bypass graft surgery (CABG).Methods:From July 2019 to May 2020, thirty-four consecutive patients selected for elective isolated on-pump coronary artery bypass graft surgery (CABG) enrolled in the trial. Patients were randomly assigned into two groups; memantine and the control group. For the memantine group, 10 mg of memantine twice daily was administered at least 72 h before surgery. Venous blood samples were collected before surgery (T1), at the end of cardiopulmonary bypass (CPB) (T2), 6h and 24h after CPB (T3 and T4). Serum concentration of S100-B was measured by enzyme-linked immunosorbent assay (ELISA) technique.Results:Serum S100-B increased during CPB with a peak plasma concentration at the termination of CPB. Then it gradually decreased during the first 24 hours in both groups (P=0.001). The mean S100-B levels were significantly lower in the memantine group compared to the control group at the termination of CPB (0.863±0.203 μg/l vs 1.117±0.304 μg/l), at 6 hours post-CPB (0.731±0.168 μg/l vs 0.938±0.206 μg/l), and 24 hours post-CPB (0.595±0.189 μg/l vs 0.852±0.227 μg/l), respectively (P=0.023). The mean level of serum S100-B in memantine group was about 0.19 μg/l less than the control group during the study (CI, 0.07 to 0.30; P=0.001). One (6.2%) patient in the control group had post-operative left arm paresthesiaConclusion:Administration of memantine before on-pump CABG can attenuate the post-operative concentrations of serum S100-B, which may reduce cerebral damage during surgery.

Effect of patient end-tidal carbon dioxide levels on cerebral regional oxygen saturation and inflammatory cytokine concentrations in elderly patients undergoing laparoscopic radical gastrectomy: a randomized controlled trial

Carbon dioxide levels can affect inflammation and cerebral regional oxygen saturation (rScO2), a pathophysiological indicator of early postoperative cognitive dysfunction (POCD).To compare the cerebral rScO2 and postoperative inflammation based on patient end-tidal carbon dioxide (PET CO2) levels in elderly patients undergoing laparoscopic radical gastrectomy. Ninety patients were randomly divided into three groups according to PET CO2 level: group L (low PET CO2, 36–40 mmHg), group C (control PET CO2, 41–45 mmHg) and group H (high PET CO2, 46–50 mmHg). Eighty-four patients (age, range: 60–80 years) scheduled to undergo radical laparoscopic gastrectomy were included in the final analysis. The indicated PET CO2 was maintained for patients in each group. Their intraoperative cerebral rScO2 was recorded at indicated timepoints (T0–T6) from arrival at the operating room to post-extubation. The Montreal Cognitive Assessment Test (MoCA) and changes in serum concentrations of inflammatory cytokines were measured at 1 h, 1d and 7 d after surgery. The cerebral rScO2 at T3 (1 h post-skin incision)–T5 (completion of skin sutures) was significantly higher in group H than in group L, while the MoCA score was not significantly different between group H and L (p &gt; 0.05). At 1 h, 1 d and 7 d after surgery, the concentrations of inflammatory cytokines, including interleukin 6 (IL-6) and S100β, were significantly higher in group L than in group H (p &lt; 0.05). At 1 h and 7 d after surgery, the inflammatory cytokines were significantly higher in group C than in group H. Our findings suggest that higher PET CO2 levels increased cerebral rScO2 and reduced the serum concentrations of IL-6 and S100β but may not affect the MoCA score in elderly patients after radical laparoscopic gastrectomy.

Regulatory mechanism of the SNHG3/miR-302a-3p/E2F1 feedback loop in nerve repair post cerebral ischemic stroke

Cerebral ischemic stroke (CIS) remains a primary cause of death worldwide. The current knowledge has identified the implication of microRNAs (miRNAs) in the pathophysiology of CIS. This study investigated the mechanism of miR-302a-3p in nerve repair post CIS. A middle cerebral artery occlusion (MCAO) model was established in mice to simulate CIS. miR-302a-3p expression in brain tissues of MCAO mice was up-regulated by injecting agomiR-302a-3p. Neurological deficits of MCAO mice were evaluated through neurological function score, forelimb placing test, and balance beam walking test. Neuronal damage was measured using Nissl staining. The concentrations of nerve injury-related factors (S100B and GFAP) and the contents of neuroinflammatory factors (TNF-α and IL-1β) in serum were examined using ELISA kits. miR-302a-3p, E2F1, and long non-coding RNA (lncRNA) SNHG3 expressions in brain tissues of MCAO mice were determined using RT-qPCR and Western blot. The binding relationships between miR-302a-3p and E2F1 and E2F1 and SNHG3 were validated using dual-luciferase and ChIP assays, respectively. miR-302a-3p expression was reduced in brain tissues of MCAO mice. miR-302a-3p overexpression increased the number of neurons, decreased the concentrations of S100B and GFAP, reduced the contents of TNF-α and IL-1β, promoted nerve repair, and alleviated CIS-induced brain injury. miR-302a-3p targeted E2F1 expression, and E2F1 activated SNHG3 transcription. E2F1 overexpression or SNHG3 overexpression reversed the effect of miR-302a-3p overexpression on nerve repair in MCAO mice. miR-302a-3p overexpression repressed SNHG3 transcription by targeting E2F1 expression, thereby promoting nerve repair and alleviating CIS.