Increase In S100B Research Articles

Increase in Plasma S100B Concentration Is Associated With Decrements in Spatial Processing During Acute High-Altitude Exposure

Vasogenic edema consequent to blood-brain barrier (BBB) permeability may contribute to cognitive performance decrements during acute exposure to high altitude. S100B is a putative marker of BBB permeability, but S100B responses to high altitude are poorly characterized and the relation to cognitive performance is unknown. To test the hypothesis that S100B increases upon ascent to high altitude and that increase is associated with changes in cognitive performance, 41 healthy Soldiers (mean±SD; age=26±5yr) were tested at their baseline residence (SL, 331m), transported to Taos, NM (2845m), then immediately hiked (n=21) or were driven (n=20) to a high-altitude (HA, 3600m) facility. Plasma S100B was measured at 06:00 throughout the study; twice at SL and again after the first night at HA (16h exposure). The automated neuropsychological assessment metric (ANAM) was administered four times at SL and once at HA to assess sustained attention, working memory, spatial processing, computation, executive function, and reaction time. ANAM performance was assessed using throughput scores, a metric considering both response speed and accuracy. The last SL morning assessment and the HA morning assessment (19h exposure) were used to generate ΔANAM scores. Correlations between ΔS100B and ΔANAM scores were significant for 1 of 9 modules, simultaneous spatial processing (SPD; r=-0.401; p=0.009). S100B increased (5.3%, p=0.02) from SL to HA while SPD scores decreased (8.2%, p=0.05). Using the reliable change index (RCI) to dichotomize individuals into those demonstrating a decrease in performance that exceeded measurement error and day-to-day variability (responders; RCI <-1.64; n=7) and those who did not (non-responders; RCI >-1.64; n=34) revealed that responders experienced a greater increase (+12.3%, p=0.01) in S100B from SL to HA relative to non-responders (+3.4%, p=0.14) Findings suggest that acute exposure to 3600m may increase BBB permeability, as indicated from plasma S100B concentrations, and the increased BBB permeability may be mechanistically associated with spatial processing decrements. Funding: USAMRDC, PRMRP. Authors’ views not offcial U.S. Army or DoD policy. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Impact of treatment on blood-brain barrier impairment in Wilson's disease.

Our study assessed changes in concentrations of serum markers for brain damage and blood-brain barrier (BBB) dysfunction in untreated and treated Wilson's disease (WD) patients, and examined correlations between these changes and neurological impairment. These results hold the potential to determine BBB impairment and neurological advancement in WD to develop the most effective treatment for patients with severe neurological deterioration. The study groups included 171 patients with WD (77 with hepatic and 94 with neurological manifestations), treated either for up to 5 or 15 years, and 88 healthy controls. Serum concentrations of intercellular adhesion molecule 1 (ICAM1), P-selectin, matrix metallopeptidase 9 (MMP9), glial fibrillary acidic protein (GFAP), and S100 calcium-binding protein B (S100B) were measured before and during anti-copper treatment. The Unified Wilson's disease Rating Scale (UWDRS) was used to assess neurological advancement. ICAM1 concentrations were elevated before and during anti-copper treatment compared to controls (p < 0.01), but therapy led to substantial decreases both in patients with hepatic (p < 0.01) and in patients with neurological manifestations (p < < 0.05). P-selectin concentrations remained elevated before and during treatment (p < 0.05) regardless of the treatment duration and disease form. MMP9 concentrations before treatment were lower (p < 0.05), but reached control levels during treatment. GFAP concentrations were significantly elevated only in untreated patients with neurological symptoms in the longer-treated group compared to controls (p < 0.05). A significant reduction during treatment was observed only in the shorter-treated neurological group (p < 0.05). No substantial changes were observed in S100B. Only ICAM1 concentrations positively correlated (r = 0.27, p < 0.001) with the UWDRS. Our results provide evidence of endothelial activation in WD. However, inconclusive GFAP results, and no increase in S100B, do not allow us to conclude whether the reactive gliosis is not prominent or alternatively whether the BBB is disrupted. Elevated ICAM1 concentrations and their correlation with neurological advancement indicate BBB impairment. A decrease in ICAM1 during treatment suggests that the inflammatory process is reduced, and the BBB partially repaired. Decreased MMP9 concentrations may be the result of active liver fibrosis and higher copper concentrations. Elevated P-selectin concentrations indicate a systemic inflammatory process.

Beyond brain injury biomarkers: chemoattractants and circulating progenitor cells as biomarkers of endogenous rehabilitation effort in preterm neonates with encephalopathy.

Preclinical work and studies in adults have shown that endogenous regeneration efforts that involve mobilization of progenitor cells take place after brain injury. However, kinetics of endogenous circulating progenitor cells (CPCs) in preterm neonates is not well described, particularly their possible role regarding brain injury and regeneration. We aimed to assess the kinetics of CPCs in neonates with encephalopathy of prematurity in relation to brain injury biomarkers, chemoattractants and relevant antenatal and postanal clinical factors, in an effort to outline the related pathophysiology. 47 preterm neonates (of 28-33 weeks GA) were enrolled: 31 newborns with no or minimal brain injury (grade I IVH) and 16 prematures with encephalopathy (grade III or IV IVH, PVL or infarct). Peripheral blood samples obtained on days 1, 3, 9, 18 and 45 after birth were analyzed using flow cytometry, focusing on EPCs (early and late Endothelial Progenitor Cells), HSCs (Hematopoietic Stem Cells) and VSELs (Very Small Embryonic-Like Stem Cells). At the same time-points serum levels of S100B, Neuron-specific Enolase (NSE), Erythropoietin (EPO), Insulin-like growth factor-1 (IGF-1) and SDF-1 were also measured. Neonates were assessed postnatally with brain MRI, and with Bayley III developmental test at 2 years of corrected age. Preterms with brain injury proved to have significant increase of S100B and NSE, followed by increase of EPO and enhanced mobilization mainly of HSCs, eEPCs and lEPCs. IGF-1 was rather decreased in this group of neonates. IGF-1 and most CPCs were intense decreased in cases of antenatal or postnatal inflammation. S100B and NSE correlated with neuroimaging and language scale in Bayley III test, providing good prognostic ability. The observed pattern of CPCs' mobilization and its association with neurotrophic factors following preterm brain injury indicate the existence of an endogenous brain regeneration process. Kinetics of different biomarkers and associations with clinical factors contribute to the understanding of the related pathophysiology and might help to early discriminate neonates with adverse outcome. Timely appropriate enhancement of the endogenous regeneration effort, when it is suppressed and insufficient, using neurotrophic factors and exogenous progenitor cells might be a powerful therapeutic strategy in the future to restore brain damage and improve the neurodevelopmental outcome in premature infants with brain injury.

Characterizing EEG and Serum Biomarker Trends in Immune Effector Cell-Associated Neurotoxicity: A Case Series (P10-1.001)

<h3>Objective:</h3> To characterize electroencephalographic (EEG) trends over time in immune effector cell-associated neurotoxicity syndrome (ICANS) and identify correlations between neuron-derived serum biomarkers of inflammation, neurotoxicity grade, and EEG findings. <h3>Background:</h3> Chimeric antigen receptor T-cell therapy (CAR-T) can be effective for refractory hematologic malignancies, but may be complicated by ICANS. Previous studies link higher peak neurotoxicity grades with EEG background abnormalities and higher incidences of rhythmic and periodic patterns (RPPs). <h3>Design/Methods:</h3> We performed a retrospective analysis of CAR-T patients who were enrolled into an IRB-approved prospective, longitudinal observational study. Data including demographics, ICE scores, and neurologic symptoms were prospectively entered. Serum biomarkers including Ang-1, Ang-2, IL-6, UCH-L1, and S100b were drawn prior to CAR-T and at defined time points thereafter. EEG data was reviewed, with encephalopathy grade defined by American Clinical Neurophysiology Society (ACNS) criteria. <h3>Results:</h3> Forty-five patients were included in the study. Ten patients (22%) developed ICANS. EEG data was available for five (11%) patients, with a median of 35 hours recorded per patient. Zero patients had confirmed electrographic seizures. Median ICE score prior to EEG was 1. Backgrounds were mildly or moderately encephalopathic, with improving organization and faster frequencies over time. GPDs or LPDs of 0.5–2Hz were rare to abundant and gradually improved with time. Focal slowing and sharp waves were common. S100b consistently increased above (average 45%) and Ang-2 decreased below (average 53%) baseline at the time of becoming symptomatic for two patients (drawn within 48 hours before/after EEG was obtained), whereas Ang-1, IL-6, and UCH-L1 had more variable changes. <h3>Conclusions:</h3> Patients with ICANS who underwent EEGs had up to moderate electrographic (and severe clinical) encephalopathy and RPPs that spontaneously improved with time. Higher encephalopathy grade occurred in those with greater S100b increases. Our observations will need to be confirmed in an independent population with serial samples and EEG data on all patients. <b>Disclosure:</b> Dr. Nguyen has nothing to disclose. Lila Renteria has nothing to disclose. Dr. Motika has nothing to disclose. Dr. Hinson has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Hinson has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for UCSF. Dr. Hinson has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for American Heart Association.

Is S100B Involved in Attention-Deficit/Hyperactivity Disorder (ADHD)? Comparisons with Controls and Changes Following a Triple Therapy Containing Methylphenidate, Melatonin and ω-3 PUFAs.

Increasing evidence supports a neuroinflammatory basis in ADHD damaging glial function and thereby altering dopaminergic (DA) neurotransmission. Previous studies focusing on the S100B protein as a marker of glial function have shown contradictory results. We conducted a clinical trial to investigate differences in S100B levels between ADHD patients and controls, as well as observe gradual changes in S100B concentrations after a triple therapy (TT) containing methylphenidate (MPH), melatonin (aMT) and omega-3 fatty acids (ω-3 PUFAs). 62 medication-naïve children with ADHD (ADHD-G) and 65 healthy controls (C-G) were recruited. Serum S100B was measured at baseline (T0) in ADHD-G/C-G, and three (T3) and six months (T6) after starting TT in the ADHD-G, together with attention scores. A significant increase in S100B was observed in the ADHD-G vs. C-G. In the ADHD-G, significantly higher S100B values were observed for comparisons between T0-T3 and between T0-T6, accompanied by a significant improvement in attention scores for the same timepoint comparisons. No significant differences were found for S100B between T3-T6. Our results agree with the hypothesis of glial damage in ADHD. Further studies on the link between DA and S100B are required to explain the transient increase in S100B following TT.

No increase in GFAP and S-100B in very preterm infants with mild periventricular leukomalacia or intraventricular hemorrhage: a pilot study

To determine the serum levels of glial fibrillary acidic protein (GFAP) and S-100B in very preterm infants with and without periventricular leukomalacia (PVL) and/or intraventricular hemorrhage (IVH). The study enrolled preterm infants born between 23 and 32 weeks of gestation admitted to the Neonatal Intensive Care Unit, University Medical Center Ljubljana. PVL and IVH were determined with cranial ultrasound. Peripheral blood was collected in the first 24 hours after delivery and once between days 4 to 7. GFAP and S-100B concentrations were measured in serum samples. Infants with PVL or IVH were compared with infants without PVL or IVH. Of 40 patients (mean gestational age 29.4 weeks), 7 had IVH and/or PVL. S-100B was detectable in peripheral blood in all patients at every measurement. In the group with IVH or PVL, the median S-100B at the first sampling was 0.43 (IQR 0.29-0.60) ng/mL, and 0.40 (IQR 0.33-1.01) ng/mL at the second sampling. In the group without PVL or IVH, it was 0.40 (IQR 0.29-0.6) ng/mL at the first sampling and 0.43 (IQR 0.34-0.62) ng/mL at the second sampling. The median GFAP was 0 regardless of the group and sampling time. The groups did not significantly differ in serum GFAP or S-100B levels. Peripheral blood levels of GFAP and S-100B were not significantly increased in very preterm infants that developed PVL or IVH. The predictive value of GFAP and S-100B as biomarkers of neonatal brain injury should be further explored in a larger cohort of neonates with more extensive IVH or PVL.

The Fundamental Role of Neuroinflammation at the Beginning and Progression of Alzheimer’s Disease

The majority of astrocytes are responsible for the expression and release of S100B, a 21-kDa calcium-binding protein of the EFhand type (helix E-loop-helix F). It is mostly present in the neurological system and, depending on concentration, has different (beneficial, detrimental) effects on neurons, astrocytes, and microglia. an effect on the survival and development of both glia and neuronal cells. Patients with Down Syndrome and Alzheimer's Disease (AD) have brains that are overexpressed with the S100 protein Down Syndrome (DS). Increased S100B concentrations are linked to brain trauma and ischemia, most likely due to astrocyte destruction. As S100B appears to influence multiple neuropathological mechanisms in (AD) , a pivotal role for S100B as a significant contributor to (AD) pathology has emerged. Studies of S100B overexpression, S100B localization, multiple relationships between S100B and increase amyloid precursor protein, the interaction between S100B and dystrophic neuritis plaques, and change in a neurofibrillary tangle in Alzheimer's disease focus on providing evidence for the involvement of S100B in Alzheimer's disease pathology and neuronal loss. The significance of S100B in head trauma and degenerative brain disease is the central subject of this review. Overexpressing s100B, which also causes more astrogliosis and microgliosis, speeds up the pathogenesis of Alzheimer's disease. Numerous clinical problems have been associated with an increase in S100B, a neurotropic signaling protein.

Potential value of serum brain-derived neurotrophic factor, vascular endothelial growth factor, and S100B for identifying major depressive disorder in knee osteoarthritis patients.

The chronic pain and functional limitations in osteoarthritis (OA) patients can increase risk of psychiatric disorders, e.g., major depression disorder (MDD), which may further aggravate the clinical symptoms of OA. Early detection of MDD is essential in the clinical practice of OA. Two hundred and fifteen participants with knee OA were recruited, including 134 MDD patients (i.e., MDD group) and 81 ones without MDD (i.e., control group). Among them, 81 OA participants in the control group received a 3-year follow-up and were divided into trans-MDD group (who transforming into MDD; N = 39) and non-MDD group (who keeping non-MDD; N = 42) at the end of the follow-up. The 17-item Hamilton Depression Scale (HAMD-17), Self-Rating Depression Scale (SDS), and Visual Analogue Scale (VAS) were performed. Furthermore, serum levels of brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF), S100B, and IGF-1 were detected. (1) Compared with OA participants without MDD, there were significant decrease in serum BDNF and significant increase in serum VEGF and S100B and VAS scores in OA participants with MDD. (2) A mediation of the association was found between the VAS scores and the HAMD-17 scores through the BDNF as mediator in OA participants with MDD. (3) Significantly lower baseline BDNF levels and higher baseline S100B levels were detected in OA participants who transforming to MDD after a 3-year follow-up when compared with those who keeping non-MDD. (4) In the trans-MDD group, significant associations of the change of serum BDNF levels with rate of change of HAMD-17 scores were found, and baseline serum S100B levels positively correlated with the HAMD-17 scores at the end of the follow-up. (5) In OA participants, the composite indicator of BDNF, VEGF, and S100B differentiated MDD patients from controls with the area under the curve (AUC) value of 0.806, and the combined indicator of baseline BDNF and S100B distinguished trans-MDD participants from non-MDD ones with an AUC value of 0.806. Serum BDNF, VEGF, and S100B may be potential biomarkers to identify MDD in OA patients. Meanwhile, serum BDNF and S100B shows great potential to predict the risk of MDD for OA.

Development of a novel bioengineered 3D brain-like tissue for studying primary blast-induced traumatic brain injury.

Primary blast injury is caused by the direct impact of an overpressurization wave on the body. Due to limitations of current models, we have developed a novel approach to study primary blast-induced traumatic brain injury. Specifically, we employ a bioengineered 3D brain-like human tissue culture system composed of collagen-infused silk protein donut-like hydrogels embedded with human IPSC-derived neurons, human astrocytes, and a human microglial cell line. We have utilized this system within an advanced blast simulator (ABS) to expose the 3D brain cultures to a blast wave that can be precisely controlled. These 3D cultures are enclosed in a 3D-printed surrogate skull-like material containing media which are then placed in a holder apparatus inside the ABS. This allows for exposure to the blast wave alone without any secondary injury occurring. We show that blast induces an increase in lactate dehydrogenase activity and glutamate release from the cultures, indicating cellular injury. Additionally, we observe a significant increase in axonal varicosities after blast. These varicosities can be stained with antibodies recognizing amyloid precursor protein. The presence of amyloid precursor protein deposits may indicate a blast-induced axonal transport deficit. After blast injury, we find a transient release of the known TBI biomarkers, UCHL1 and NF-H at 6 h and a delayed increase in S100B at 24 and 48 h. This in vitro model will enable us to gain a better understanding of clinically relevant pathological changes that occur following primary blast and can also be utilized for discovery and characterization of biomarkers.

Diagnostic performance of early increase in S100B or LDH as outcome predictor for non-responsiveness to anti-PD-1 monotherapy in advanced melanoma

As a subset of advanced melanoma patients derive long-term benefit from anti-PD-1 therapy, early identification of non-responsiveness would enable an early switch to next line therapies. This study assessed if an early increase in S100B or lactate dehydrogenase (LDH) could be predictive for non-responsiveness to anti-PD-1. We retrospectively analysed advanced melanoma patients treated with anti-PD-1 monotherapy. Serum S100B and LDH levels were measured at baseline and before every infusion. Non-response was defined as progression or death at 6 months. Marker cut-offs were defined based on > 95% specificity and feasibility in clinical practice. For validation an independent cohort was analysed. In total, 313 patients were included (166 patients in training cohort, 147 patients in validation cohort). Increase of > 50% in LDH or > 100% in S100B above upper limit of normal at week 6 compared to baseline was determined as criterion to positively test for non-responsiveness. In the validation cohort, obtained specificity of the combination test was > 95% with a positive predictive value of 82%; obtained sensitivity was lower (21%), with a negative predictive value of 55%. Early increase in S100B or LDH is a strong parameter for non-responsiveness to anti-PD-1 in advanced melanoma. Prospective confirmation is needed before clinical implementation.

The triangle correlation among the impact on serum S100B protein release, incidence of the silent cerebral ischemic phenomena and pulsed field ablation for patients with atrial fibrillation

Abstract Funding Acknowledgements Type of funding sources: None. Backgrounds: Pulsed field ablation (PFA) represents a cardiac specific energy source for atrial fibrillation (AF) ablation. The correlation among this remarkable technique, the incidence of silent cerebral ischemic phenomena (SCIP), and the clinical impact on serum S100B release, a well-known neural injury relevant biomarker concomitant to denervation of the intrinsic cardiac autonomic nervous system during AF ablation, has been unclear. Aims This study thought to reveal the "triangle correlation" by investigating the serum S100B increase, incidence of SCIP on cerebral magnetic resonance imaging (MRI), and its interactive correlation in PFA using the FARAPULSE system. Methods and Results Pre- and postprocedural serum S100B was analyzed in a total of 85 patients who underwent AF ablation using the FARAPULSE PFA device. Cerebral MRI was performed subsequently 24-48 hours after procedure. All PVs (332 PVs) were successfully isolated solely with PFA. No additional left atrial mapping using other catheters was performed. The median overall serum S100B increase from the preprocedural value was 0.01μg/l (-0.02 – 0.04μg/l). Asymptomatic SCIP were detected on MRI in 10/53 patients (18.9 %). Of those, the patients with SCIP demonstrated a significantly higher S100B release (0.04, 0.02 – 0.16μg/l vs. without SCIP:0.01, -0.04 – 0.03μg/l, p = 0.0038). Receiver operating characteristic curve revealed a predictive cut-off point for SCIP of 0.04 μg/l (sensitivity:0.7, specificity: 0.49). Conclusions We revealed no clear detectable impact of PFA on S100B release, highlighting the cardioselectivity with limited concomitant denervation. SCIP was detected approximately in a one-fifth after procedures and was a potential confounder of the higher S100B increase.

T006 Increase in S100B and LDH as early outcome predictors for non-responsiveness to anti-PD1 monotherapy in advanced melanoma

T006 Increase in S100B and LDH as early outcome predictors for non-responsiveness to anti-PD1 monotherapy in advanced melanoma

Postoperative delirium and changes in the blood–brain barrier, neuroinflammation, and cerebrospinal fluid lactate: a prospective cohort study

BackgroundCase-control studies have associated delirium with blood–brain barrier (BBB) permeability. However, this approach cannot determine whether delirium is attributable to high pre-existing permeability or to perioperative changes. We tested whether perioperative changes in cerebrospinal fluid/plasma albumin ratio (CPAR) and plasma S100B were associated with delirium severity. MethodsParticipants were recruited to two prospective cohort studies of non-intracranial surgery (NCT01980511, NCT03124303, and NCT02926417). Delirium severity was assessed using the Delirium Rating Scale-98. Delirium incidence was diagnosed with the 3D-Confusion Assessment Method (3D-CAM) or CAM-ICU (CAM for the ICU). CSF samples from 25 patients and plasma from 78 patients were analysed for albumin and S100B. We tested associations between change in CPAR (n=11) and S100B (n=61) and delirium, blood loss, CSF interleukin-6 (IL-6), and CSF lactate. ResultsThe perioperative increase in CPAR and S100B correlated with delirium severity (CPAR ρ=0.78, P=0.01; S100B ρ=0.41, P<0.001), delirium incidence (CPAR P=0.012; S100B P<0.001) and CSF IL-6 (CPAR ρ=0.66 P=0.04; S100B ρ=0.75, P=0.025). Linear mixed-effect analysis also showed that decreased levels of S100B predicted recovery from delirium symptoms (P=0.001). Linear regression demonstrated that change in plasma S100B was independently associated with surgical risk, cardiovascular surgery, blood loss, and hypotension. Blood loss also correlated with CPAR (ρ=0.64, P=0.04), S100B (ρ=0.70, P<0.001), CSF lactate (R=0.81, P=0.01), and peak delirium severity (ρ=0.36, P=0.01). ConclusionPostoperative delirium is associated with a breakdown in the BBB. This increased permeability is dynamic and associated with a neuroinflammatory and lactate response. Strategies to mitigate blood loss may protect the BBB.

Correlation between S100B and severity of depression in MDD: A meta-analysis

Background Previous studies have demonstrated elevated levels of the S100B protein (located in glial cells) in major depressive disorder (MDD) as compared to healthy controls. However, studies reporting correlation between S100B levels and depression severity have been conflicting. Methods We investigated, through systematic review and meta-analysis, whether the correlation between S100B levels and depression severity is significant in patients with MDD. Pearson correlation coefficients reported in the individual studies were converted to Fisher’s Z scores, then pooled using the random effects model. Meta-regression was used to test modifiers of the effect size. Results Sixteen studies including 658 patients with MDD met eligibility criteria. No publication bias was observed. There was a significant and positive correlation between serum S100B level and depression severity (r = 0.204, z = 2.297, p = 0.022). A meta-regression determined that onset age of MDD and percentage of female participants are significant modifiers of this correlation. A moderate, but non-significant heterogeneity was observed in serum studies (44%). Conclusion As many studies have reported significantly increased levels of S100B in MDD compared to controls, this meta-analysis supports the assumption that the increase in S100B correlates with the severity of MDD. Additional studies investigating the precise biological connection between S100B and MDD are indicated.

S100B as a biomarker of blood-brain barrier disruption after thoracoabdominal aortic aneurysm repair: a secondary analysis from a prospective cohort study.

The objective of this study was to determine whether the magnitude of the peripheral inflammatory response to cardiovascular surgery is associated with increases in blood-brain barrier (BBB) permeability as reflected by changes in cerebrospinal fluid (CSF)/plasma S100B concentrations. We conducted a secondary analysis from a prospective cohort study of 35 patients undergoing elective thoracoabdominal aortic aneurysm repair with (n = 17) or without (n = 18) cardiopulmonary bypass (CPB). Plasma and CSF S100B, interleukin-6 (IL-6), and albumin concentrations were measured at baseline (C0) and serially for up to five days. Following CPB, the median [interquartile range] plasma S100B concentration increased from 58 [32-88] pg·mL-1 at C0 to a maximum concentration (Cmax) of 1,131 [655-1,875] pg·mL-1 over a median time (tmax) of 6.3 [5.9-7.0] hr. In the non-CPB group, the median plasma S100B increased to a lesser extent. There was a delayed increase in CSF S100B to a median Cmax of 436 [406-922] pg·mL-1 in the CPB group at a tmax of 23.7 [18.5-40.2] hr. In the non-CPB group, the CSF concentrations were similar at all time points. In the CPB group, we did not detect significant correlations between plasma and CSF S100B with plasma IL-6 [r = 0.52 (95% confidence interval [CI], -0.061 to 0.84)] and CSF IL-6 [r = 0.53 (95% CI, -0.073 to 0.85)] concentrations, respectively. Correlations of plasma or CSF S100B levels with BBB permeability were not significant. The lack of parallel increases in plasma and CSF S100B following CPB indicates that S100B may not be a reliable biomarker for BBB disruption after thoracoabdominal aortic aneurysm repair employing CPB. www.clinicaltrials.gov (NCT00878371); registered 7 April 2009.

Effects of Vitamin C and Dimethylsulfoxide (Dmso) on Neuro-Behaviour, Apoptosis and oxidative stress in ischaemic stroke induced rats

Background: Researches over the years have identified excitotoxicity, oxidative stress, inflammation and cell death as key contributors underlying progression of lesion in ischaemic stroke (IS). This study reports the effect of vitamin C and dimethylsulfoxide (DMSO) in the management of ischaemic stroke (IS) in Wistar rats. Method: Forty rats were divided into four groups of ten rats each. Groups 1, 2 and 3 were induced with IS by middle cerebral artery occlusion (MCAO). Anxiety like behavior and locomotor activity assessments were carried out. Group 1was treated with vitamin C (67.5mg/kg) and group 2 with DMSO (67.5mg/kg) orally for two weeks. Group 4 was neither induced nor treated. Brain tissue homogenates (cerebral cortex) were assessed for the level of calcium binding protein (S100B), antioxidant enzymes [Superoxide dismutase (SOD), Catalae (CAT), Glutathion peroxidase (GPx)] gene expressions, BCL2, Bax and Caspase3. Result: The results of this study showed that in the IS rats, there was significant (P&lt;0.05) increase in anxiety and a significant (P&lt;0.05) decrease in the locomotor activity. There was also significant (P&lt;0.05) increase in S100B, caspase 3 and Bax expressions, while there was significant (P&lt;0.05) decrease in BCL2. Treatment with vitamin C and DMSO resulted in significant (P&lt;0.05) increase in the locomotor activity and significant (P&lt;0.05) decrease in anxiety. There was significant (P&lt;0.05) increase in the expression of SOD, CAT and GPx genes. Also, there was significant (P&lt;0.05) decrease in S100B level, caspase-3 and Bax expressions, while there was significant (P&lt;0.05) increase in BCL2. Conclusion: Conclusively, the results of this research highlighted the potentials for the use of vitamin C and DMSO in the management of IS. Keywords: Stroke; Antioxidant; Locomotor; Neuro-Behavioural; Dimethylsulfoxide Apoptosis; Oxidative Stress

Oxidative Stress and Serum S100B Levels in Adolescents with First-Episode Drug-Naive Unipolar Depression.

Unipolar depression is common among adolescents and has high recurrence rates. Studies conducted with adults show that oxidative stress plays a role in etiology of depression but studies with adolescent patients are limited. In addition, baseline S100B level in adult patients with depression is considered as a marker of response to treatment. The purpose of this study was to measure the levels of serum S100B, Malondialdehyde (MDA), total oxidant status (TOS), and total antioxidant status (TAS), which have not been previously investigated in adolescent patients with first-episode, drug-naive unipolar depression, and to investigate the relationship of these parameters with disease severity and patient-specific variables. This study was conducted with 37 adolescents diagnosed with unipolar depression and 37 healthy peers. Participants were asked to fill out the Beck Depression Scale, Screen for Child Anxiety Related Disorders, and suicide probability questionnaires. After this procedure, 5 cc blood was collected from the adolescents and serum S100B, MDA, TOS, and OSI levels measured. Serum S100B, MDA, TOS, and OSI levels were higher and TAS level was lower in patients than their healthy peers. There was no relationship between the patients' severity of depression or suicide probability and these parameters. The serum S100B, MDA, TOS, and OSI levels of female patients were higher than their healthy peers, but the TAS level was not different. Male patients had higher TOS and OSI levels and lower TAS levels than their healthy peers. The results show that increased serum S100B, MDA, TOS and OSI levels may contribute to etiology of depression regardless of gender. The gender-specific increase in S100B and MDA levels, which were significantly increased in female adolescent patients but not in males, should be supported by further follow-up studies.

Role of S100b protein and BDNF in immunopathogenesis of neuroinflammation in the patients with induced immunocompromised state

Post-operation cognitive dysfunctions, related to mild manifestations of neurological pathology occuring after surgery, represent an important challenge for both fundamental and clinical medicine. The underlying phenomena of neuroinflammation are still poorly understood and discutable. The studies in immunopathogenesis of neuroinflammation may help in understanding the development of pathology and suggest ways to solve this problem. A special role for implementation of this process belongs to neuropeptides. Objective: to characterize immunopathogenesis of neuroinflammation in the individuals with immunocompromised state induced during aorto-coronary bypass surgery. A total of 110 patients with ischemic heart disease who underwent myocardial revascularization under extracorporeal circulation conditions were examined. Pathological neuroinflammation was recognized by development of postoperative cognitive dysfunction based on changing results of the cognitive examination (Montreal scale, MoCa test). The patients were tested before intervention, and on day 7 after surgery. According to the test results, all the patients were divided into 2 groups: (1) without signs of postoperative cognitive dysfunction and (2) with the mentioned signs. Venous blood was collected four times, on the day of surgery before the intervention, immediately after the surgery, 24 hours later, and on the 7th day after surgery. S100b and BDNF contents were determined in the venous blood serum. The baseline level of the S100b protein in the study groups did not differ from the reference values. After surgery, an increase in S100b was observed in both groups, but in patients with emerging postoperative cognitive dysfunction, these indexes were significantly higher. Despite a tendency for stabilization, the increased level of neuropeptides persisted 24 hours after the surgery; on the 7th day, the index was within the reference values, but in the 1st group it was lower than in the 2nd group. Prior to the operation, the BDNF level was significantly higher in the patients from group 1, compared with group 2. In the second group, the index was lower than the values obtained from the control group volunteers. After surgery, the values of BDNF in blood serum showed some differences: immediately after surgery, the level of neuropeptide was higher in patients without cognitive dysfunction. On day 7, the level of BDNF was within reference values, but in patients from group 2, the values were higher than in group 1.

Sintocalmy, a Passiflora incarnata Based Herbal, Attenuates Morphine Withdrawal in Mice.

Chronic opioid use changes brain chemistry in areas related to reward processes, memory, decision-making, and addiction. Both neurons and astrocytes are affected, ultimately leading to dependence. Passiflora incarnata L. (Passifloraceae) is the basis of frequently used herbals to manage anxiety and insomnia, with proven central nervous system depressant effects. Anti-addiction properties of P. incarnata have been reported. The aim of this study was to investigate the effect of a commercial extract of Passiflora incarnata (Sintocalmy®, Aché Laboratory) in the naloxone-induced jumping mice model of morphine withdrawal. In addition, glial fibrillary acidic protein (GFAP) and S100 calcium-binding protein B (S100B) levels were assessed in the frontal cortex and hippocampus, and DNA damage was verified on blood cells. In order to improve solubilization a Sintocalmy methanol extract (SME) was used. SME is mainly composed by flavonoids isovitexin and vitexin. The effects of SME 50, 100 and 200mg/kg (i.p.) were evaluated in the naloxone-induced withdrawal syndrome in mice. SME 50 and SME 100mg/kg decreased naloxone-induced jumping in morphine-dependent mice without reducing locomotor activity. No alterations were found in GFAP levels, however SME 50mg/kg prevented the S100B increase in the frontal cortex and DNA damage. This study shows anti-addiction effects for a commercial standardized extract of P. incarnata and suggests the relevance of proper clinical assessment.

Circulating neurotrophins and hemostatic risk factors of atherothrombotic cardiovascular disease at baseline and during sympathetic challenge: the SABPA study

Sympathetic activation may trigger acute coronary syndromes. We examined the relation between circulating neurotrophic factors and hemostatic risk factors of atherothrombotic cardiovascular disease at baseline and in response to acute mental stress to establish a brain–heart link. In 409 black and white South Africans, brain-derived neurotrophic factor (BDNF) and fibrinolytic measures were assessed at baseline. Glial cell-derived neurotrophic factor (GDNF), S100 calcium-binding protein (S100B), von Willebrand factor (VWF), fibrinogen and D-dimer were assessed at baseline and 10 min after the Stroop test. Neurotrophins were regressed on hemostatic measures adjusting for demographics, comorbidities, cardiometabolic factors and health behaviors. Higher baseline BDNF was associated with greater stress-induced increase in fibrinogen (p = 0.003) and lower D-dimer increase (p = 0.016). Higher baseline S100B was significantly associated with higher baseline VWF (p = 0.031) and lower fibrinogen increase (p = 0.048). Lower baseline GDNF was associated with higher baseline VWF (p = 0.035) but lower VWF increase (p = 0.001). Greater GDNF (p = 0.006) and S100B (p = 0.042) increases were associated with lower VWF increase. All associations showed small-to-moderate effect sizes. Neurotrophins and fibrinolytic factors showed no significant associations. The findings support the existence of a peripheral neurothrophin-hemostasis interaction of small-to-moderate clinical relevance. The implications for atherothrombotic cardiovascular disease need further exploration.