Blood Astrocyte Biomarkers in Alzheimer Disease: A Systematic Review and Meta-Analysis.

BACKGROUND AND OBJECTIVES: Neuroinflammation, particularly early astrocyte reactivity, is a significant driver of Alzheimer disease (AD) pathogenesis. It is unclear how the levels of astrocyte biomarkers change in patients across the AD continuum and which best reflect AD-related change. We performed a systematic review and meta-analysis of 3 blood astrocyte biomarkers (glial fibrillary acidic protein [GFAP], chitinase-3-like protein 1 [YKL-40], and S100B) in patients clinically diagnosed with AD. METHODS: MEDLINE and Web of Science were searched on March 23, 2023, without restrictions on language, time, or study design, for studies reporting blood levels of the astrocyte biomarkers GFAP, YKL-40, or S100B in patients on the AD continuum (including those with mild cognitive impairment [MCI] and dementia) and a cognitively unimpaired (CU) control population. AD diagnosis was based on established diagnostic criteria and/or comprehensive multidisciplinary clinical consensus. Studies reporting indirect biomarker measures (e.g., levels of biomarker autoantibodies) were excluded. Risk of bias assessment was performed using the revised Quality Assessment of Diagnostic Accuracy Studies tool. Pooled effect sizes were determined using the Hedge g method with a random-effects model. The review was prospectively registered on PROSPERO (registration number CRD42023458305). RESULTS: The search identified 1,186 studies; 36 met inclusion criteria (AD continuum n = 3,366, CU n = 4,115). No study was assessed to have a high risk of bias. Compared with CU individuals, patients on the AD continuum had higher GFAP and YKL-40 levels (GFAP effect size 1.15, 95% CI 0.94-1.36, p < 0.0001; YKL-40 effect size 0.38, 95% CI 0.28-0.49, p < 0.0001). Both biomarkers were elevated in more advanced clinical stages of the disease (i.e., in AD dementia compared with MCI due to AD: GFAP effect size 0.48, 95% CI 0.19-0.76, p = 0.0009; YKL-40 effect size 0.34, 95% CI 0.10-0.57, p = 0.0048). No significant differences in blood S100B levels were identified. DISCUSSION: We demonstrated significant elevations in blood GFAP and YKL-40 levels in patients on the AD continuum compared with CU individuals. Furthermore, within the AD clinical spectrum, significant elevation correlated with more advanced disease stage. Our findings suggest that both biomarkers reflect AD-related pathology. Our findings are limited by the lack of cultural and linguistic diversity in the study populations meta-analyzed. Future meta-analyses using a biomarker-defined AD population are warranted.

Altered blood parameters in "major depression" patients receiving repetitive transcranial magnetic stimulation (rTMS) therapy: a randomized case-control study.

Major depressive disorder (MDD) is a debilitating illness that includes depressive mood. Repetitive Transcranial Magnetic Stimulation (rTMS) is a therapy method used in the treatment of MDD. The purpose of this study was to assess neurotrophic factors, and oxidative stress levels in MDD patients and evaluate the changes in these parameters as a result of rTMS therapy. Twenty-five patients with MDD and twenty-six healthy volunteers with the same demographic characteristics were included in the study. Brain-derived neurotrophic factors were measured photometrically with commercial kits. Oxidative stress parameters were measured by the photometric method. Oxidative stress index (OSI) and disulfide (DIS) levels were calculated with mathematical formulas. In this study, total antioxidant status (TAS), total thiol (TT), and native thiol (NT) antioxidant parameters and brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), and allopregnanolone (ALLO) levels were reduced in pre-rTMS with regard to the healthy control group; TOS, OSI, DIS, and S100 calcium-binding protein B (S100B) levels were increased statistically significantly (p < 0.01). Moreover, owing to TMS treatment; TAS, TT, NT, BDNF, GDNF, and ALLO levels were increased compared to pre-rTMS, while DIS, TOS, OSI, and S100B levels were decreased significantly (p < 0.01). The rTMS treatment reduces oxidative stress and restores thiol-disulfide balance in MDD patients. Additionally, rTMS modulates neurotrophic factors and neuroactive steroids, suggesting its potential as an antidepressant therapy. The changes in the biomarkers evaluated may help determine a more specific approach to treating MDD with rTMS therapy.

Altered serum levels of neuronal proteins and antibodies to them in occupational diseases of the nervous system.

Aclinical and immunological examination of men with occupational pathology, including vibration disease (VD), occupational sensorineural hearing loss (SHL), and chronic mercury intoxication (CMI), was carried out. The comparison group consisted of men comparable in age and total work experience. Serum concentrations of neurotrophins (S100ß, MBP, BDNF) and antibodies (ABs) to S100ß and MBP proteins were determined by enzyme-linked immunosorbent assay. An increase in the level of the S100ß protein was shown in CMI, VD, and a tendency for its increase was found in SHL. In parallel, an increase in AB to the S100ß protein in VD and SHL and a decrease in AB in CMI were noted. A comparative assessment of MBP levels indicated a pronounced increase in its serum concentrations in patients with CMI and VD versus the comparison group. At the same time, an increase in the level of serum ABs to MBP in individuals with VD and SHL, and a decrease in patients with CMI were noted. In patients with CMI, a significant decrease in the BDNF concentration was found, while in SHL and VD, no statistically significant differences were found in comparison with the comparison group. The results obtained confirm importance of assessing serum concentrations of neurotrophic proteins and ABs to them in the case of occupational damage to the nervous system caused by exposure to physical and chemical factors.

Reconsidering S100B: Why it is time to abandon its use in detecting disease recurrence in stage III melanoma patients.

BACKGROUND: Especially in the era of successful systemic therapy, there is an urgent need to detect early disease recurrence in stage III melanoma patients. This study investigates if serum S100 calcium-binding protein B (S100B) can detect disease recurrence in stage III melanoma patients. METHODS: A retrospective cohort study was conducted at the University Medical Center Groningen (UMCG). Adult AJCC 8th stage III melanoma patients in whom serum S100B was measured as part of follow-up from January 2010 until April 2023 were included. The association between serum S100B and disease recurrence was evaluated using standard definitions for sensitivity and positive predictive value (PPV). RESULTS: Overall, 147 patients were included (mean age was 60.4 years, 53.1 % were female). Most patients were classified as stage IIIB (39, 26.5 %) and IIIC (73, 49.7 %). During median follow-up of 56 months, 69 (46.9 %) patients experienced disease recurrence. Seventeen out of 18 patients with elevated serum S100B (≥0.15 µg/L) experienced disease recurrence (PPV of 94.4 %). However, 52 out of 69 patients with disease recurrence had normal serum S100B (sensitivity of 24.6 %). Eight out of 17 (47.1 %) patients were asymptomatic (P = 0.608), twelve (70.6 %) patients had at least four distant metastases (P < 0.001). CONCLUSION: The clinical value of serum S100B to detect disease recurrence in stage III melanoma patients is negligible since only one out of four patients with disease recurrence have elevated serum S100B. Furthermore, half of stage III melanoma patients with elevated S100B experienced symptoms, and most patients already have multiple distant metastases.

Gender differences in plasma S100B levels of patients with major depressive disorder.

BACKGROUND: Low concentrations of S100B have neurotrophic effects and can promote nerve growth and repair, which plays an essential role in the pathophysiological and histopathological alterations of major depressive disorder (MDD) during disease development. Studies have shown that plasma S100B levels are altered in patients with MDD. In this study, we investigated whether the plasma S100B levels in MDD differ between genders. METHODS: We studied 235 healthy controls (HCs) (90 males and 145 females) and 185 MDD patients (65 males and 120 females). Plasma S100B levels were detected via multifactor assay. The Mahalanobis distance method was used to detect the outliers of plasma S100B levels in the HC and MDD groups. The Kolmogorov-Smirnov test was used to test the normality of six groups of S100B samples. The Mann-Whitney test and Scheirer-Ray-Hare test were used for the comparison of S100B between diagnoses and genders, and the presence of a relationship between plasma S100B levels and demographic details or clinical traits was assessed using Spearman correlation analysis. RESULTS: All individuals in the HC group had plasma S100B levels that were significantly greater than those in the MDD group. In the MDD group, males presented significantly higher plasma S100B levels than females. In the male group, the plasma S100B levels in the HC group were significantly higher than those in the MDD group, while in the female group, no significant difference was found between the HC and MDD groups. In the male MDD subgroup, there was a positive correlation between plasma S100B levels and years of education. In the female MDD subgroup, there were negative correlations between plasma S100B levels and age and suicidal ideation. CONCLUSIONS: In summary, plasma S100B levels vary with gender and are decreased in MDD patients, which may be related to pathological alterations in glial cells.

Antibody-labeled gold nanoparticle based resonance Rayleigh scattering detection of S100B.

Traumatic brain injury (TBI) is a sudden brain injury due to an external force that causes a large number of deaths and permanent disabilities every year. S100B has been recognized as a potential objective quantitative biomarker for screening the prognosis of TBI and severe head injury. In this article, an anti-S100B monoclonal antibody was immobilized on cysteamine (Cy) functionalized gold nanoparticles (AuNPs) by EDC-NHS chemistry, which enabled S100B resonance Rayleigh scattering (RRS) detection based on antibody-labeled gold nanoparticles. The prepared conjugates were characterized by ultraviolet-visible spectroscopy (UV-vis), transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR), dynamic light scattering (DLS) and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Based on the specific binding of the antibody and antigen, the RRS intensities at 381 nm and 541 nm wavelengths were significantly enhanced, and thus a dual wavelength overlapping resonance Rayleigh scattering (DWO-RRS) method was established. The scattering intensity of the two overlapping peaks was proportional to the concentration of S100B in the range of 0.05-4.5 ng mL-1 with a detection limit of 0.002 ng mL-1. The proposed DWO-RRS method is time-saving, simple, sensitive, and can be used to determine the concentration of S100B in human serum with satisfactory results, which has a promising application in the early diagnosis of TBI.

Blood brain barrier permeability and astrocyte-derived extracellular vesicles in children with juvenile idiopathic arthritis: a cross-sectional study.

BACKGROUND: Juvenile idiopathic arthritis (JIA) is the most prevalent rheumatic disease in children, and the inflammatory process is widely studied, primarily characterized by its impact on joint health. Emerging evidence suggests that JIA may also affect the central nervous system (CNS). This study investigates the potential CNS involvement in JIA by analyzing the presence of astrocyte-derived extracellular vesicles (EVs) and the S100B protein in plasma, both of which are indicative of astrocyte activity and blood-brain barrier (BBB) integrity. METHODS: EDTA plasma from 90 children diagnosed with JIA and 10 healthy controls, matched by age and gender, was analyzed for extracellular vesicles by flow cytometric measurement. Astrocyte-derived EVs were identified using flow cytometry with markers for aquaporin 4 (AQP-4) and glial fibrillary acidic protein (GFAP). Levels of the S100B protein were measured using a commercial ELISA. Disease activity was assessed using the Juvenile Arthritis Disease Activity Score (JADAS27, 0-57), and pain levels were measured using a visual analogue scale (VAS, 0-10 cm). RESULTS: Our analyses revealed a significantly higher concentration of astrocyte-derived EVs in the plasma of children with JIA compared with healthy controls. Furthermore, children with JADAS27 scores of 1 or higher exhibited notably higher levels of these EVs. The S100B protein was detectable exclusively in the JIA group. CONCLUSION: The elevated levels of astrocyte-derived EVs and the presence of S100B in children with JIA provide evidence of BBB disruption and CNS involvement, particularly in those with higher disease activity. These findings underscore the importance of considering CNS health in the comprehensive management of JIA. Further research is required to elucidate the mechanisms behind CNS engagement in JIA and to develop treatments that address both joint and CNS manifestations of the disease.

[Expression and significance of hypoxia-inducible factor 1α and Bcl-2/adenovirus E1B19kDa-interacting protein 3 in children with traumatic brain injury]. / ç¼ºæ°§è¯±å¯¼å› å­1α、Bcl-2/è ºç— æ¯’E1B19kDa相互作用蛋白3在儿童创伤性脑损伤中的表达及意义.

OBJECTIVES: To dynamically observe the changes in hypoxia-inducible factor 1α (HIF-1α) and Bcl-2/adenovirus E1B19kDa-interacting protein 3 (BNIP3) in children with traumatic brain injury (TBI) and evaluate their clinical value in predicting the severity and prognosis of pediatric TBI. METHODS: A prospective study included 47 children with moderate to severe TBI from January 2021 to July 2023, categorized into moderate (scores 9-12) and severe (scores 3-8) subgroups based on the Glasgow Coma Scale. A control group consisted of 30 children diagnosed and treated for inguinal hernia during the same period, with no underlying diseases. The levels of HIF-1α, BNIP3, autophagy-related protein Beclin-1, and S100B were compared among groups. The predictive value of HIF-1α, BNIP3, Beclin-1, and S100B for the severity and prognosis of TBI was assessed using receiver operating characteristic (ROC) curves. RESULTS: Serum levels of HIF-1α, BNIP3, Beclin-1, and S100B in the TBI group were higher than those in the control group (P<0.05). Among the TBI patients, the severe subgroup had higher levels of HIF-1α, BNIP3, Beclin-1, and S100B than the moderate subgroup (P<0.05). Correlation analysis showed that the serum levels of HIF-1α, BNIP3, Beclin-1, and S100B were negatively correlated with the Glasgow Coma Scale scores (P<0.05). After 7 days of treatment, serum levels of HIF-1α, BNIP3, Beclin-1, and S100B in both non-surgical and surgical TBI patients decreased compared to before treatment (P<0.05). ROC curve analysis indicated that the areas under the curve for predicting severe TBI based on serum levels of HIF-1α, BNIP3, Beclin-1, and S100B were 0.782, 0.835, 0.872, and 0.880, respectively (P<0.05), and for predicting poor prognosis of TBI were 0.749, 0.775, 0.814, and 0.751, respectively (P<0.05). CONCLUSIONS: Serum levels of HIF-1α, BNIP3, and Beclin-1 are significantly elevated in children with TBI, and their measurement can aid in the clinical assessment of the severity and prognosis of pediatric TBI.

Predictive value of S100B and brain derived neurotrophic factor for radiofrequency treatment of lumbar disc prolapse.

BACKGROUND: This work aimed to analyze serum S100B levels and brain-derived neurotrophic factor (BDNF) in patients with lumbar disc prolapse to test their predictive values concerning the therapeutic efficacy of pulsed radiofrequency. METHODS: This prospective interventional study was carried out on 50 patients candidates for radiofrequency for treating symptomatic lumbar disc prolapse. Pain severity and functional disability were assessed using the Numeric Rating Scale (NRS) and Functional rating index (FRI) before as well as two weeks, 1, 3, and 6 months after the radiofrequency. Quantitative assessment of serum S100B level and BDNF was done for all the included patients one day before radiofrequency. RESULTS: The scores of NRS and FRI were significantly improved at two weeks, 1, 3, and 6 months following radiofrequency (P-value < 0.001 in all comparisons). Statistically significant positive correlations were found between duration of pain, NRS, and S100B serum level before radiofrequency, and both NRS (P-value = 0.001, 0.035, < 0.001 respectively) and FRI (P-value = < 0.001, 0.009, 0.001 respectively) 6 months following radiofrequency. Whereas there were statistically significant negative correlations between BDNF serum level before radiofrequency and both NRS and FRI 6 months following radiofrequency (P-value = 0.022, 0.041 respectively). NRS and S100B serum levels before radiofrequency were found to be independent predictors of NRS 6 months following radiofrequency (P-value = 0.040. <0.001, respectively). CONCLUSION: Serum level of S100B is a promising biomarker that can predict functional outcomes after pulsed radiofrequency in patients with lumbar disc prolapse.

Plasma neurological biomarkers as a measure of neurotoxicity in pediatric dental general anesthesia: a prospective observational feasibility study.

PURPOSE: Neurotoxicity concerns have been raised over general anesthesia and sedation medication use in children. Such concerns are largely based on animal studies, historical anesthetic agents, and assessment tools, thus warranting further investigations. Blood biomarkers in detecting neuronal inflammation and apoptosis are novel methods for detecting neuronal damage. Therefore, the aim of this feasibility study was to assess the usefulness of the levels of four plasma biomarkers in dental general anesthesia (DGA) as surrogate markers of neurotoxicity in children. The secondary aim was to compare changes in motor manipulative skills pre- and post-anesthetic exposure. METHODS: This single-center prospective observational study included 22 healthy children aged between 3 and 6 years old who underwent DGA. Subclinical neurotoxicity was measured with a panel of four plasma biomarkers: Caspase-3, neuron-specific enolase (NSE), neurofilament light chain, and S100B at three time points (1; at start, 2; end and 3; on recovery from DGA). The Skillings-Mack test was used to identify the difference in the biomarker levels at three time points. Motor manipulative score assessment, prior and two weeks after DGA was also performed. RESULTS: A total of 22 study participants (mean age = 5 ± 1 years) were included with a median DGA duration of 106 ± 28 min. A reduction in Caspase-3 levels was recorded, with pairwise comparison over three time points, reporting a statistical significance between time point 2 vs. 1 and time point 3 vs. 1. Although fluctuations in NSE levels were recorded, no significant changes were found following pairwise comparison analysis. Among other biomarkers, no significant changes over the three periods were recorded. Furthermore, no significant changes in manipulative motor scores were reported. CONCLUSION: Caspase-3 reduced significantly in the short time frames during day-care DGA; this might be due to the relatively short anesthesia duration associated with dental treatment as compared with more extensive medical-related treatments. Therefore, further studies on Caspase-3 as a potential biomarker in pediatric DGA neurotoxicity are required to further ascertain results of this study.

Minor head injury in anticoagulated patients: performance of biomarkers S100B, NSE, GFAP, UCH-L1 and Alinity TBI in the detection of intracranial injury. A prospective observational study.

OBJECTIVES: Data in literature indicate that in patients suffering a minor head injury (MHI), biomarkers serum levels could be effective to predict the absence of intracranial injury (ICI) on head CT scan. Use of these biomarkers in case of patients taking oral anticoagulants who experience MHI is very limited. We investigated biomarkers as predictors of ICI in anticoagulated patients managed in an ED. METHODS: We conducted a single-cohort, prospective, observational study in an ED. Our structured clinical pathway included a first head CT scan, 24 h observation and a second CT scan. The outcome was delayed ICI (dICI), defined as ICI on the second CT scan after a first negative CT scan. We assessed the sensitivity (SE), specificity (SP), negative predictive value (NNV) and positive predictive value (PPV) of the biomarkers S100B, NSE, GFAP, UCH-L1 and Alinity TBI in order to identify dICI. RESULTS: Our study population was of 234 patients with a negative first CT scan who underwent a second CT scan. The rate of dICI was 4.7 %. The NPV for the detection of dICI were respectively (IC 95 %): S100B 92.7 % (86.0-96.8 %,); ubiquitin C-terminal hydrolase-L1 (UCH-L1) 91.8 % (83.8-96.6 %); glial fibrillary protein (GFP) 100 % (83.2-100 %); TBI 100 % (66.4-100 %). The AUC for the detection of dICI was 0.407 for S100B, 0.563 for neuron-specific enolase (NSE), 0.510 for UCH-L1 and 0.720 for glial fibrillary acidic protein (GFAP), respectively. CONCLUSIONS: The NPV of the analyzed biomarkers were high and they potentially could limit the number of head CT scan for detecting dICI in anticoagulated patients suffering MHI. GFAP and Alinity TBI seem to be effective to rule out a dCI, but future trials are needed.

Antenatal corticosteroids-to-delivery interval associates cord blood S100B levels.

AIM: Antenatal corticosteroids (ACS) are recommended for women at risk of preterm birth before 34 weeks' gestation. However, adverse effects of ACS on the fetal brain have also been reported. The time interval from ACS administration to delivery (ACS-to-delivery interval) might alter the effect of ACS on the fetal brain. This study aimed to evaluate the effect of ACS-to-delivery interval on cord blood S100 calcium-binding protein B (S100B) levels as a biomarker of brain damage. METHODS: Women who delivered between 2012 and 2020 at a tertiary medical center were divided into three groups according to ACS use and ACS-to-delivery interval, retrospectively: non-ACS, ACS ≤7 days, and ACS >7 days. Patients who did not complete the ACS regimen were excluded. The primary outcome was cord blood S100B levels. RESULTS: Cord blood S100B levels were significantly lower in the ACS ≤7 days group than in the non-ACS and ACS >7 days groups. In the multiple regression analysis, birth ≤7 days after ACS showed a significant negative association with S100B level (p < 0.001). CONCLUSIONS: Reduced S100B levels were observed in infants born ≤7 days after ACS but not in infants born >7 days after ACS. These findings suggest the importance of ACS timing to optimize its effects on the fetal brain, although further studies are required to identify these mechanisms.

COMPARATIVE EVALUATION AND PROGNOSTIC UTILITY OF NEURONAL INJURY BIOMARKERS IN COVID-19 PATIENTS: A PROSPECTIVE STUDY.

ABSTRACT: Background : COVID-19 disease severity markers include mostly molecules related to not only tissue perfusion, inflammation, and thrombosis, but also biomarkers of neural injury. Clinical and basic research has demonstrated that SARS-COV-2 affects the central nervous system. The aims of the present study were to investigate the role of neural injury biomarkers and to compare them with inflammatory markers in their predictive ability of mortality. Methods : We conducted a prospective observational study in critically ill patients with COVID-19 and in a cohort of patients with moderate/severe disease. S100b, neuron-specific enolase (NSE), and inflammatory markers, including soluble urokinase plasminogen activator receptor (suPAR), were measured on intensive care unit or ward admission, respectively. Statistical comparisons between patient groups were performed for all biomarkers under investigation. Correlations between different biomarkers were tested with Spearman correlation coefficient. Receiver operating characteristic curves were plotted using mortality as the classification variable and the biomarker levels on admission as the prognostic variables. Results : A total of 70 patients with COVID-19 were included in the final analysis. Of all studied biomarkers, s100b had the best predictive ability for death in the intensive care unit, with an area under the curve of 0.73 (0.61-0.83), P = 0.0003. S100b levels correlated with NSE, interleukin (IL)-8, and IL-10 (0.27 < rs < 0.37, P < 0.05), and tended to correlate with suPAR ( rs = 0.26, P = 0.05), but not with the vasopressor dose ( P = 0.62). Conclusion : Among the investigated biomarkers, s100b demonstrated the best predictive ability for death in COVID-19 patients. The overall biomarker profile of the patients implies direct involvement of the nervous system by the novel coronavirus.

MMP-9, TIMP-1 and S100B protein as markers of ischemic stroke in patients after carotid artery endarterectomy.

Ischemic stroke is the main cause of permanent disability in adult patients. No commonly accepted method were discovered to predict stroke before the first symptoms. Activation of matrix metalloproteinases (MMPs), tissue inhibitor of metalloproteinases (TIMP) and S100B protein may be observe in patients with symptomatic carotid artery stenosis. Hemorrhagic transformation of ischemic stroke may be associated with changes in MMP, TIMP and S100B. AIM: The aim of this study was to determine if MMP-9, TIMP-1 and S-100B protein may markers of forthcoming ischemic stroke in patients undergoing carotid endarterectomy. MATERIALS AND METHODS: Blood samples were taken and an analysis of circulating proteins (MMP-9, TIMP-1, S100B) 73 subsequent patients with carotid artery stenosis ≥70% (33 asymptomatic and 40 symptomatic), who were referred for potential revascularization. RESULTS: A statistically significant difference was found between MMP- 9 levels in patients with ischemic stroke compared to patients with asymptomatic carotid stenosis after endarterectomy. Also, average TIMP-1 levels in patients with ischemic stroke and stenosis ≥70% were statistically significantly higher than the average levels in patients after endarterectomy. In terms of S-100B, a higher mean value was observed in patients with stroke than in endarterectomy group. No statistical differences were found in the levels of that proteins in the hemorrhagic transformation of ischemic stroke. CONCLUSIONS: Increased levels of MMP-9, TIMP-1 and S-100B in patients with ischemic stroke compared to patients with asymptomatic carotid stenosis after endarterectomy showed that abovementioned proteins may be a good predictive factor of ischemic stroke in patients undergoing carotid endarterectomy.

Development of a strategy for assessing blood-brain barrier disruption using serum S100 calcium-binding protein B and neuron-specific enolase in early stage of neuroemergencies: A preliminary study.

BACKGROUND: Rapid disease progression in neuroemergencies is associated with blood-brain barrier (BBB) disruption. We investigated a less invasive strategy for assessing BBB status by evaluating S100 calcium-binding protein B (S100B) and neuron-specific enolase (NSE) at early stages of the hypoxic-ischemic brain injury (HIBI) cascade. METHODS: This retrospective study used prospectively collected data from patients with out-of-hospital cardiac arrest (August 2019-July 2021). Albumin specimens obtained from serum and cerebrospinal fluid via arterial catheter and lumbar puncture were used to measure the albumin quotient (Qa), which is widely accepted as the gold standard method for detecting BBB disruption. Serum S100B and NSE levels were measured simultaneously following the return of spontaneous circulation. We conducted linear regression to evaluate the relationship between S100B and Qa and the predictive performance of S100B for abnormal Qa. The primary study outcome was abnormal Qa (>0.007). RESULTS: Forty-one patients were enrolled; 30 showed an abnormal Qa suggestive of BBB disruption. S100B levels were significantly higher than in those with a normal Qa (0.244 µg/L [interquartile range [IQR], 0.146-0.823 vs 0.754 µg/L [IQR, 0.317-2.228], P = .03). We report a positive correlation between serum S100B and Qa (R2 = 0.110; P = .04). The area under the receiver operating characteristics curve (AUROC) evaluating the predictive performance of S100B with respect to abnormal Qa was 0.718 (95% confidence interval, 0.556-0.847). The cutoff value for S100B (with respect to BBB disruption) in the total cohort was 0.283 µg/L (sensitivity, 80.0%; specificity, 72.7%). Subgroup analyses in patients with serum neuron-specific enolase (NSE) levels of <40.8 ng/mL (excluding those with established neuronal cell injury) showed an improved correlation coefficient (R2 = 0.382; P < .01) and predictive performance (AUROC, 0.836 [95% confidence interval, 0.629-0.954]) compared with the total cohort. CONCLUSIONS: Serum S100B obtained at an early stage of the HIBI cascade is associated with abnormal Qa, suggesting BBB disruption. The predictive performance of S100B and the correlation between serum S100B and Qa can be improved using a complementary strategy (i.e., evaluations of S100B and NSE levels) that combines considerations of cell damage in astrocytes and neurons.

Plasma levels of S100B and neurofilament light chain protein in stress-related mental disorders.

The pathophysiological changes underlying stress-related mental disorders remain unclear. However, research suggests that alterations in astrocytes and neurons may be involved. This study examined potential peripheral markers of such alterations, including S100B and neurofilament light chain (NF-L). We compared plasma levels of S100B and NF-L in patients with chronic stress-induced exhaustion disorder (SED), patients with major depressive disorder (MDD), and healthy controls. We also investigated whether levels of S100B and NF-L correlated with levels of astrocyte-derived extracellular vesicles (EVs that indicate astrocyte activation or apoptosis) and with symptom severity. Only women had measurable levels of S100B. Women with SED had higher plasma levels of S100B than women with MDD (P < 0.001) and healthy controls (P < 0.001). Self-rated symptoms of cognitive failures were positively correlated with levels of S100B (rs = 0.434, P = 0.005) as were depressive symptoms (rs = 0.319, P < 0.001). Plasma levels of astrocyte-derived EVs were correlated with levels of S100B (rs = 0.464, P < 0.001). Plasma levels of NF-L did not differ between the groups and were not correlated with symptom severity or EV levels. Thus, long-term stress without sufficient recovery and SED may be associated with raised plasma levels of S100B, which may be evidence of pathophysiological changes in astrocytes. The findings also support the hypothesis that plasma levels of S100B are associated with cognitive dysfunction.

Stress-induced cardiac troponin T, S100B and estradiol responses in defensive copers: The SABPA study.

Ineffective stress-coping in Africans is associated with cardiac ischemia during acute mental stress. Ischemic conditions may be worsened by stress-induced release of glial-derived S100­calcium-binding-protein ß (S100B), which is pro-apoptotic for cardiomyocytes. Whether estradiol as coping regulator and cardio-protective factor will protect against pro-apoptotic effects, remains unclear. Therefore, we aimed to investigate stress-induced associations between cardiac troponin T/cTnT (cardiac ischemic marker), S100B and estradiol in a bi-ethnic cohort of defensive copers of both sexes. The target population study included African and Caucasian teachers of both sexes (n = 344; aged 20-65 years). The Stroop-color-word-conflict-test was administrated for 1 min to induce acute mental stress in the participants. A chronic stress risk phenotype score was obtained. The Coping Strategy Indicator determined habitual defensive/avoidance/seeking social support coping scores. Fasting blood samples were obtained prior to and 10 min post-Stroop-stress to assess cTnT, S100B and estradiol levels. An interaction between ethnicity, sex and defensive coping (p < 0.05) was found for acute stress-induced percentage changes in estradiol. In defensive coping African men, the Stroop-color-word-conflict-test elicited decreases in S100B and increases in estradiol. Again, in this group, S100B decreases were related to unchanged cTnT, a chronic stress risk phenotype and acute estradiol increases (p < 0.05). No associations among main markers were apparent in the African women or the Caucasian defensive copers of both sexes. In the defensive coping African men, the markers studied may play a relevant role in the brain-cardiovascular system interaction during stress exposure. Further research is needed to elaborate on potential mechanisms and to establish clinical relevance.

Clinical Value of Serum Neuron-Specific Enolase Combined with Serum S100B Protein in the Diagnosis of Systemic Lupus Erythematosus.

Objective: To investigate the clinical value of serum neuron-specific enolase (NSE) combined with serum S100B protein in the diagnosis of systemic lupus erythematosus (SLE). Methods: Sixty patients with SLE treated in our hospital from January 2019 to April 2021 were enrolled as the study group. According to the degree of activity, the study group was assigned into three groups: mild activity group (n = 20), moderate activity group (n = 20), and severe activity group (n = 20). A total of 60 healthy people who underwent physical examination in our hospital in the same period were enrolled as the control group. The NSE and serum S100B protein were detected in the two groups, and the correlation between serum nerve-specific enolase and serum S100B protein and the clinical value in the diagnosis of SLE were analyzed. Results: First of all, we compared the general data of the two groups. There was no significant difference in sex, age, marital status, and education level, and no significant difference was exhibited (p > 0.05). There was no significant difference in sex, age, marital status, and education level among mild activity group, moderate activity group, and severe activity group, and no significant difference in data was exhibited (p > 0.05). Secondly, we compared the levels of serum S100B protein and NSE. The levels of serum S100B protein and NSE in the study group were higher compared to the control group (p < 0.05). The levels of serum S100B protein and NSE in patients with different activity levels of SLE were compared. The levels of serum S100B protein and NSE in mild activity group < moderate activity group < severe activity group were significantly different (p < 0.05). Correlation analysis between serum S100B, NSE levels, and SLE activity indicated that serum S100B and NSE levels were positively correlated with SLE activity. With the increase of SLE activity, serum S100B and NSE levels gradually increased, and the data difference was statistically significant (r = 0.855, 0.844, p < 0.05). Finally, we established the logistic prediction model, take the probability of generating prediction as the analysis index, and draw the ROC curve to evaluate the diagnostic value of different combinations to SLE. The highest AUC and sensitivity of the two indexes in the diagnosis of SLE were 0.773 and 0.836, respectively. The levels of serum S100B protein and NSE have a certain value in the diagnosis of SLE, while the combined diagnosis is of higher value, sensitivity, and specificity in the diagnosis of SLE. Conclusion: Serum S100B protein and NSE are very sensitive indexes to judge the damage of central nervous system. However, due to the small number of cases in this study, there were as many as 19 kinds of NPSLE classification, so the relationship between serum S100B protein, NSE levels, and various NPSLE and their exact application value in diagnosing the disease and judging the prognosis needs to be confirmed by expanding the number of cases.

The relationship between serum levels of S-100ß and anxiety symptoms in patients with acute stroke.

BACKGROUND: Post-stroke anxiety (PSA) is a common neuropsychiatric affective disorder occurring after a stroke. Animal experiments have indicated that serum S-100ß levels are closely related to anxiety disorder. No clinical study has been done to explore the relationship between serum S-100ß levels and anxiety symptoms in patients with acute stroke. The aim of our study was to investigate the association between serum S-100ß levels and PSA. METHODS: One hundred twenty-six acute stroke patients were recruited and followed up for 1 month. Blood samples were collected within 24 h after admission. The levels of serum S-100ß were measured by enzyme-linked immunosorbent assays. Patients with significant clinical symptoms of anxiety and a Hamilton Anxiety Rating Scale score >7 at 1 month after stroke were diagnosed as PSA. RESULTS: Serum S-100ß levels in the non-PSA group were lower than the PSA group (838.97 (678.20-993.59) ng/L vs. 961.87 (796.09-1479.59) ng/L, Z = -2.661, P = 0.008). In multivariate analyses, we found that decreased risk of PSA was associated with low tertile serum S-100ß levels (≤753.8 ng/L, OR 0.062, 95% CI 0.008-0.475, P = 0.007). CONCLUSIONS: Low serum S-100ß levels at admission may be associated with the decreased risk of PSA.

Serum S100B protein after electroconvulsive therapy in patients with depression.

OBJECTIVE: S100B is a glial cell protein with bimodal function. In low concentrations, it exerts neurotrophic effects, but higher levels reflect neuronal distress. Recent research suggests that this molecule may be a biomarker of response to electroconvulsive therapy (ECT). We examined the effect of ECT on serum S100B and its utility as 1) a biomarker of a depressive state and 2) a predictor of ECT response. We also wanted to ensure that ECT does not cause a marked serum S100B elevation, indicating neural distress. METHODS: We measured serum S100B in 22 in-patients treated with ECT due to depression. Depression severity was assessed using 17-item Hamilton Rating Scale for Depression (HAMD-17). The data were collected before an ECT series, within 1 week after the series (post-ECT), and at a 6-month follow-up. Changes in serum S100B and clinical outcomes were tested using a linear mixed model. A relationship between serum S100B and the clinical outcomes was examined using Spearman's and partial correlation. RESULTS: Serum S100B did not change significantly immediately after an ECT series or 6 months later. The post-ECT serum S100B change was not associated with the clinical effect (rho = 0.14, n = 22, p = 0.54). The baseline serum S100B did not predict the clinical effect when controlling for age (r = 0.02, n = 22, df = 19, p = 0.92). CONCLUSION: The study neither supports serum S100B as a state marker of depression nor a predictor of ECT response. No evidence for ECT-related neural distress was found.