High S100B Research Articles

S100b/RAGE-dependent chemoattraction of microglia

The Ca2+-binding protein of the EF-hand type, S100B, is abundantly expressed in and released by astrocytes, and leakage of S100B from damaged astrocytes occurs during the course of acute and chronic brain disorders [1]. Thus, the concept has emerged that S100B might act an unconventional cytokine or a damage-associated molecular pattern protein playing a role in the pathophysiology of neurodegenerative disorders and inflammatory brain diseases. S100B’s pro-inflammatory effects require relatively high concentrations of the protein, while at physiological concentrations S100B exerts trophic effects on neurons. Most, if not all of the extracellular (trophic and toxic) effects of S100B in the brain are mediated by the engagement of RAGE (receptor for advanced glycation end products) [1-2]. For example, high S100B activates RAGE-dependently microglia, stimulating the release of IL-1β and TNF-α and upregulating the expression of the proinflammatory enzyme, COX-2 [3-4]. We show here that high S100B chemoattracts murine microglia via RAGE engagement and RAGE-dependent activation of Src kinase, Ras, PI3K, MEK/ERK1/2, RhoA/ROCK, Rac1/JNK/AP-1, Rac1/NF-κB and, to a lesser extent, p38 MAPK. Recruitment of the adaptor protein, diaphanous-1, a member of the formin protein family, is also required for S100B/RAGE-dependent chemoattraction of microglia. The S100B/RAGE-dependent activation of diaphanous-1/Rac1/JNK/AP-1, Ras/Rac1/NF-κB and, likely, Src/Ras/PI3K/RhoA/diaphanous-1 results in the upregulation of expression of the chemokines, CCL3, CCL5 and CCL12, the release and activity of which are required for S100B to chemoattract microglia. Lastly, RAGE engagement by S100B in microglia results in upregulation of the chemokine receptors, CCR1 and CCR5. These results suggests that S100B might participate in the pathophysiology of brain inflammatory disorders via RAGE-dependent regulation of several inflammationrelated events including attraction and activation of microglia.

A study of correlation between the anti-schizophrenia effects of risperidone and the levels of S100B protein

Objective To explore the correlation between the anti-schizophrenia effects of Risperidone and the levels of S100B protein for clinical rational use of drug. Methods The therapy effect of Risperidone treating 60 patients with schizophrenia would be appraised by PANSS score evaluation, and the blood drug levels were assayed by HPLC-MS for curative dose, furthermore the concentrations of S100B were detected by ELISA, analyzing the correlation between the and-schizophrenia effects of Risperidone and the levels of S100B protein. Results The steady plasma-drug concentrations of Risperidone and 9-hydroxyl-Risperidone had no statistical difference; compared with the evaluation score before treatment, many patients were improved in the 4th week, which had statistical significance (P<0.05) ; and compared with the levels of S100B before therapy, it would reduce in the 2nd week, which had statistical significance (P<0.05) ; moreover the Pearson correlation coefficients of S100B levels and PANSS Total, PANSS negative score and PANSS positive score were r=0.860(P<0.01) , r= 0.847( P = 0.01) and r = 0.589( P=0.044) respectively; at the end of the 6th week, the S100B levels of the patients with ineffective (12 cases) or effective (48 cases) Risperidone treatment were (0.12 ±0.07)μg· L~(-1) and (0.03±0.01)μg·L~(-1) respectively, which had statistical significance (P = 0.007). Conclusion Risperidone is much effective for the patients with schizophrenia and could reduce the high S100B levels in plasma to a certain extent; the S100B protein closed correlated with the anti-schizophrenia effects of Risperidone and the pathogenetic condition of patient, which has an important clinical significance. Key words: Risperidone; Schizophrenia; S100B

Diabetic conditions promote binding of monocytes to vascular smooth muscle cells and their subsequent differentiation

Diabetes is associated with significantly accelerated rates of atherosclerosis, key features of which include the presence of excessive macrophage-derived foam cells in the subendothelial space. We examined the hypothesis that enhanced monocyte-vascular smooth muscle cell (VSMC) interactions leading to subendothelial monocyte retention and differentiation to macrophages under diabetic conditions may be underlying mechanisms. Human aortic VSMCs (HVSMCs) treated with diabetic stimuli high glucose (HG) or S100B, a ligand of the receptor for advanced glycation end products, exhibited significantly increased binding of THP-1 monocytic cells. Diabetic stimuli increased the expression of the adhesive chemokine fractalkine (FKN) in HVSMCs. Pretreatment of HVSMCs with FKN or monocyte chemoattractant protein-1 (MCP-1) neutralizing antibodies significantly inhibited monocyte-VSMC binding, whereas monocytes treated with FKN showed enhanced binding to VSMC. Mouse aortic VSMCs (MVSMCs) derived from type 2 diabetic db/db mice exhibited significantly increased FKN levels and binding to mouse WEHI78/24 monocytic cells relative to nondiabetic control db/+ cells. The enhanced monocyte binding in db/db cells was abolished by both FKN and MCP-1 antibodies. Endothelium-denuded aortas from db/db mice and streptozotocin-induced diabetic mice also exhibited enhanced FKN expression and monocyte binding, relative to respective controls. Coculture with HVSMCs increased CD36 expression in THP-1 cells, and this was significantly augmented by treatment of HVSMCs with S100B or HG. CD36 mRNA and protein levels were also significantly increased in WEHI78/24 cells after coincubation with db/db MVSMCs relative to control MVSMCs. These results demonstrate that diabetic conditions may accelerate atherosclerosis by inducing key chemokines in the vasculature that promote VSMC-monocyte interactions, subendothelial monocyte retention, and differentiation.

Amniotic fluid S100B protein and erythropoietin in pregnancies at risk for fetal hypoxia

Objective S100B protein is a biochemical marker for brain injury, and high serum S100B levels have been observed in newborns with birth asphyxia. We hypothesized that the concentration of amniotic fluid erythropoietin, which increases in chronic fetal hypoxia, correlates with amniotic fluid S100B concentration. Study design Amniotic fluid samples in 35 pregnancies at high risk for chronic fetal hypoxia were obtained at cesarean section or by amniocentesis done within a median of 2 days before delivery. S100B and erythropoietin concentrations were measured by chemiluminescent immunoassays. Results A positive correlation existed between the concentrations of S100B and erythropoietin in the amniotic fluid ( r = 0.57, p < 0.0001). Amniotic fluid S100B concentration was higher (70 ng/l; 33–469, n = 17) (median; range) in pregnancies with elevated amniotic fluid erythropoietin (≥50 IU/l) than in pregnancies with normal erythropoietin (34 ng/l; 20–340, n = 18) ( p < 0.0001, Mann–Whitney U-test). S100B predicted an elevated amniotic fluid erythropoietin concentration in the study population with the sensitivity of 94% and specificity of 83%. Conclusion A strong positive correlation exists between amniotic fluid S100B and erythropoietin concentrations in pregnancies at high risk for chronic fetal hypoxia. This suggests that chronic fetal hypoxia increases the intrauterine release of S100B.

339: High Serum S100B Levels in Patients With Acute Bone Fractures Without Cerebral Injuries

339: High Serum S100B Levels in Patients With Acute Bone Fractures Without Cerebral Injuries

S100B as an additional prognostic marker in subarachnoid aneurysmal hemorrhage*

Studies of new neuroprotective approaches in patients with subarachnoid aneurysmal hemorrhage and better family information would benefit from the development of laboratory markers of brain ischemia. The goal of this study was to evaluate mean 15-day S100B for predicting outcomes after subarachnoid aneurysmal hemorrhage. Single center prospective cohort with consecutive inclusions. Anesthesiology and Critical Care Neurosurgical Unit of a university hospital. One hundred nine patients admitted within 48 hrs after subarachnoid aneurysmal hemorrhage onset and treated by surgical clipping or coiling within 48 hrs following admission. We recorded initial World Federation of Neurologic Surgeons and Fisher grades; comorbidities; initial severity; aneurysm location; presence of acute hydrocephalus; presence of intraventricular hemorrhage; initial seizures and neurogenic lung edema; initial troponin values; treatment of aneurysm; and occurrence of vasospasm. S100B was assayed daily over the first 15 days. Glasgow Outcome Scores were recorded at intensive care unit discharge and after 6 and 12 months. The main outcome criterion was the 12-month Glasgow Outcome Scale score dichotomized as poor (Glasgow Outcome Scale 1-3) or good (Glasgow Outcome Scale 4-5). Seventy percent of patients had good 12-month outcome. Poor outcome was associated with higher initial World Federation of Neurologic Surgeons and Fisher scores, neurogenic lung edema, high mean 15-day S100B but not initial, troponin initial value, intraventricular hemorrhage, angiographically documented vasospasm, all in an univariate manner. After multivariate analysis, only mean 15-day S100B value significantly predicted outcome (p < 0.0005). The best cutoff for the mean 15-day S100B value was 0.23 microg/L (specificity 0.90, 95% confidence interval [CI] 0.81-0.95; sensitivity 0.91, 95% CI 0.75-0.98; area under the curve 0.98, 95% CI 0.87-0.99). S100B elevation over the first 15 days after subarachnoid aneurysmal hemorrhage is associated with poor outcome after subarachnoid aneurysmal hemorrhage. This result supports the use of S100B as a surrogate marker for brain ischemia in patients with subarachnoid aneurysmal hemorrhage.

Memory impairment correlates with increased S100B serum concentrations in patients with chronic schizophrenia

Astrocyte activation indicated by increased S100B is considered a potential pathogenic factor for schizophrenia. To investigate the relationship between astrocyte activation and cognitive performance, S100B serum concentration, memory performance, and psychopathology were assessed in 40 first-episode and 35 chronic schizophrenia patients upon admission and after four weeks of treatment. Chronic schizophrenia patients with high S100B were impaired concerning verbal memory performance (AVLT, Auditory Verbal Learning Test) compared to chronic and first-episode patients with low S100B levels. The findings support the hypothesis that astrocyte activation might contribute to the development of cognitive dysfunction in schizophrenia.

Evaluation of Subclinical Cerebral Injury and Neuropsychologic Function in Patients Undergoing Carotid Endarterectomy

We examined subclinical alterations of cerebral function during carotid endarterectomy (CEA) and predictability of minor cerebral damage by perioperative levels of biochemical markers of brain damage (S100B and neuron-specific enolase [NSE]). Twenty consecutive patients with > or =70% asymptomatic carotid stenosis undergoing elective CEA were enrolled. Pre- and postoperative testing included magnetic resonance imaging (MRI) of the head, a standardized neurological exam, a battery of neuropsychological tests, and measurement of serum levels of S100B and NSE. There were no major ischemic strokes. In one patient, a mild weakness of the contralateral lower extremity was discovered on neurological examination; in another individual, postoperative MRI revealed two new small subcortical lesions without clinical correlate. While S100B increased significantly early after opening of the carotid clamp (p = 0.015), the NSE increase did not reach statistical significance. As a group, participants obtained a significantly higher mean overall neuropsychological score at follow-up testing (p < 0.05). In one patient, a significant decline of cognitive function was observed. This was the only individual to obtain a consistently high S100B and NSE increase. Neuropsychological testing combined with measurements of S100B and NSE may improve sensitivity when assessing subtle cerebral damage following CEA.

S100B in bone marrow aspirates in healthy individuals and malignant melanoma patients

The aim of this study was to evaluate S100B in bone marrow (BM) plasma from malignant melanoma patients. BM aspirates and peripheral blood (PB) plasma from 56 patients and BM aspirates from 29 healthy volunteers were collected. S100B was measured using an immune radiometric assay, which is a two-site sandwich assay based on monoclonal antibodies recognizing the beta-subunit. In the control population, the median S100B level in BM plasma was 9.0 microg/l (26 women and three men), an unexpectedly high value compared with the median S100B level in PB<0.05 microg/l. S100B levels in BM seems to be sex dependent. Median S100B levels in samples taken from male melanoma patients was 26.7 microg/l in contrast to 9.3 microg/l in female patients (Mann-Whitney P<0.002). The elevated BM S100B in melanoma patients could not be explained by presence of melanoma cells in the BM, as the values also were increased to the same extent in patients with no detectable BM metastases. In attempts to identify the source of S100B in BM, cytospins from five patients with high S100B values were stained, but none of the BM cells stained positive. S100B levels in PB were dependent on the stage of melanoma disease and there was a significant shorter survival time in the group of patients with elevated S100B compared with the group with normal S100B values, (log rank test: P=0.04). In BM taken from melanoma patients, however, there were no association between S100B levels and survival. The median S100B level in BM aspirates from healthy female volunteers and BM samples from female melanoma patients were 8.1 and 9.3 microg/l both manifold higher than the cut-off value for S100B in PB (0.2 microg/l). The median S100B in the samples taken from male melanoma patients was nearly three times higher than in the female patients. Unlike S100B in PB, S100B in BM demonstrated no prognostic value. The explanation for the unexpected high S100B in BM remains elusive.

Serum S100B Levels and Major Depressive Disorder: Its Characteristics and Role in Antidepressant Response

ObjectiveS100B is a neurotrophic factor that is involved in neuroplasticity. Neuroplasticity is disrupted in depression; however, treatment with antidepressants can restore neuroplasticity. S100B has previously been used as a biological marker for neuropathology and neuroplasticity; therefore, in this study, we compared serum S100B levels in depressive patients to those of normal controls. In addition, we compared the serum S100B levels of antidepressant responders to those of nonresponders.MethodsThirty five normal controls and 59 depressive patients were enrolled in this study. Depressive patients entered a 6 week clinical trial that included treatment with antidepressants. The serum S100B levels and clinical assessments, which included Hamilton depression rating scores, were measured at baseline and after 6 weeks of treatment with antidepressants. The difference in the serum S100B levels between depressive patients and normal controls and between antidepressant responders and nonresponders was then compared.ResultsThere were no significant differences in the serum S100B levels of normal controls and depressive patients. In addition, 30 of the depressive patients responded to antidepressant treatment while 29 did not. Finally, the responders had significantly higher baseline serum S100B levels than the nonresponders.ConclusionThe results of this study suggest that the baseline serum S100B level is associated with the subsequent response to antidepressants. In addition, the high baseline serum S100B level that was observed in depressive patients may enhance neuroplasticity, which results in a favorable therapeutic response to antidepressants.

Predictors of 1-year outcome after coiling for poor-grade subarachnoid aneurysmal hemorrhage

To describe features in patients admitted to the intensive care unit (ICU) for poor-grade aneurysmal subarachnoid hemorrhage (SAH) and to identify predictors of 12-month outcome. We conducted a controlled observational study of 51 consecutive patients treated with endovascular coiling within 96 h of rupture for poor-grade aneurysmal SAH (20 men and 31 women, age 54 +/- 12 years). We recorded co-morbidities; initial severity; aneurysm location; occurrence of acute hydrocephalus, initial seizures, and/or neurogenic lung edema; troponin values, Fisher grade; computed tomography (CT) findings; treatment intensity; and occurrence of vasospasm. The brain injury marker S100B was assayed daily over the first 8 days. Glasgow Outcome Scores (GOS) were recorded at ICU discharge, at 6 and 12 months. The main outcome criterion was the 1-year GOS score, which we used to classify patients as having a poor outcome (GOS 1-3) or a good outcome (GOS 4-5). Overall, clinical status after 1 year was very good (GOS 5) in 41% of patients and good (GOS 4) in 16%. Neither baseline characteristics nor interventions differed significantly between patients with good outcome (GOS 4-5) and those with poor outcome (GOS 1-3). Persistent intracranial pressure elevation and higher mean 8-day S100B value significantly and independently predicted the 1-year GOS outcome (P = 0.008 and P = 0.001, respectively). Patients in poor clinical condition after SAH have more than a 50:50 chance of a favorable outcome after 1 year. High mean 8-day S100B value and persistent intracranial hypertension predict a poor outcome (GOS 1-3) after 1 year.

KIOM-79 inhibits high glucose or AGEs-induced VEGF expression in human retinal pigment epithelial cells

We evaluated whether KIOM-79, a mixture of extracts obtained from Puerariae lobata, Magnolia officinalis, Glycyrrhiza uralensis and Euphorbia pekinensis, could inhibit vascular endothelial growth factor (VEGF) expression in human retinal pigment epithelial (RPE) cells cultured under high glucose (HG, 25 mM) or S100b (a specific ligand of the receptor for advance glycation end products (RAGE), 5 μg/ml). In this study, the effect of KIOM-79 on HG or S100b-induced VEGF expression was investigated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, RT-PCR, ELISA, and Western blot on human RPE cells. The MTT assay ( p < 0.01) revealed that KIOM-79 (up to 1 mg/ml) had no effect on cell growth. HG or S100b induced an increase in expression of VEGF at both mRNA and protein levels ( p < 0.05; p < 0.01 versus control). The increase in VEGF expression by HG or S100b was dose- and time-dependently prevented by KIOM-79 ( p < 0.05 versus 25 mM glucose; p < 0.01 versus S100b). Also, KIOM-79 inhibited protein kinase C (PKC)-α/β α and p38 mitogen-activated protein kinase (MAPK) activation. Our results demonstrate that KIOM-79 can inhibit VEGF expression via inhibition of the MAPK and PKC pathway.

Effect of magnolol on TGF-β1 and fibronectin expression in human retinal pigment epithelial cells under diabetic conditions

Magnolol, a natural product isolated from Magnolia officinalis, has various pharmacological effects, such inhibition of effect on inflammation and tumor metastasis, protection against cerebral ischaemic injury, and potent antioxidant activity. In this present study, we evaluated the inhibitory effects of magnolol on transforming growth factor-β1 (TGF-β1) and fibronectin expression induced by high concentrations of glucose or S100b (a specific receptor of advance glycation end products ligand) in human retinal pigment epithelial cells (human RPE cells). No effect on cell growth was found with magnolol (up to 20 μg/ml) using a colorimetric 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltertrazolium bromide (MTT) assay. High glucose (25 mM) or S100b (5 μg/ml) induced increases in expression of TGF-β1 and fibronectin. The increases in TGF-β1 and fibronectin expression with high glucose or S100b were prevented by magnolol in a dose-dependent manner. Also, magnolol inhibited extracellular signal-regulated kinase (ERK)/mitogen-activated protein kinase (MAPK)/Akt activation. The present study demonstrates that high glucose- or S100b-induced TGF-β1 and fibronectin expression, but this increased expression is inhibited by magnolol via the ERK/MAPK/Akt signaling pathway in human RPE cells.

S-100B and NSE: markers of initial impact of subarachnoid haemorrhage and their relation to vasospasm and outcome

S100-B and neuron specific enolase (NSE) are known predictors of outcome in head injured and stroke patients. This study was conducted to test the hypothesis that S-100B and NSE can predict the development of vasospasm and outcome within the first 3 days after subarachnoid haemorrhage (SAH). Fifty-one SAH patients (mean age 51 ± 11 years, male : female ratio 1.0 : 1.6, mean World Federation of Neurological Surgeons [WFNS] Grade 3 ± 1.5) were included in the study. S100-B and NSE were recorded in venous blood across the first 3 days post-SAH. Vasospasm was diagnosed if mean blood flow velocity of the middle cerebral artery was greater than 120 cm/s and Lindegaard ratio >3. Glasgow Outcome Score (GOS) and cranial CT scans were recorded at 6 months. Normal, intermediate and high S-100B values were seen in 24%, 51% and 25% of patients, respectively. In patients with S-100B > 1 μg/L, Fisher Grade 4 and WFNS 4–5 were both seen in 77% of cases. S-100B was significantly higher in those patients who did not develop vasospasm. In addition, S-100B values were significantly higher in those patients who died than in those with unfavourable or favourable outcome. NSE was normal, intermediate and high in 82%, 8% and 10% of patients, respectively. Patients with WFNS 4–5 and/or Fisher Grade 4 had significantly higher NSE values than all others. Across the first 3 days after SAH, measuring S-100B is useful to predict outcome and vasospasm.

Urinary S-100B Concentrations in Term and Preterm Infants at Risk for Brain Damage

Background: Elevated serum concentrations of S-100B, a 21-kDa protein expressed in astroglial cells, has been used to assess cerebral damage after head trauma, infection, ischemia, and perinatal asphyxia. Objective: As S-100B is eliminated by the kidneys, we investigated the feasibility of measuring S-100B in urine of newborns with severe perinatal asphyxia, and in very low birth weight (VLBW) preterm infants at risk for neurodevelopmental impairment. Methods: We first analyzed urine samples of 8 term or near-term newborns without major medical problems, followed by urine samples of 2 term newborns with severe birth asphyxia, and finally urine samples of 8 VLBW (gestational age 24–28 weeks) infants collected every 4 h for up to 10 days. Results: Urinary S-100B concentrations in 8 term or near-term newborns without major medical problems were consistently <1 µg/l. In 2 term newborns with severe asphyxia (Apgar 0/0/0 and 0/2/4) who subsequently had widespread cerebral damage on magnetic resonance imaging, peak urinary S-100B concentrations on the first day of life were 28.1 and 28.4 µg/l, respectively. In 5/8 VLBW infants, urinary S-100B was >1 µg/l in samples obtained on the first day of life (range 1.2–44.9 µg/l, median 6.8 µg/l). Peak S-100B in urine samples collected during the first 12 h of life were negatively related to gestational age (R_s = –0.882, p = 0.009). Three of the 8 preterm infants had peak urinary concentrations >10 µg/l but neither ultrasound signs of brain damage nor neurodevelopmental delay at 1 year corrected age. Conclusions: The determination of urinary S-100B concentrations might be helpful in term infants with severe asphyxia, while high urinary S-100B concentrations in preterm infants are to be attributed to immaturity.

High Maternal Blood S100B Concentrations in Pregnancies Complicated by Intrauterine Growth Restriction and Intraventricular Hemorrhage

Intrauterine growth restriction (IUGR) is associated with perinatal mortality and with neurologic damage from intraventricular hemorrhage (IVH). We investigated whether S100B, a neural protein found in high concentrations after cell injury in the nervous system, is increased in serum of women whose pregnancies are complicated by IUGR and whose newborns develop IVH. We also explored the prognostic accuracy of maternal serum S100B for IVH in the newborn. We conducted a case-control study of 106 pregnancies complicated by IUGR, including a subgroup (n = 26) who developed IVH after birth, and 212 unaffected pregnancies matched for gestational age. Ultrasound examination, Doppler velocimetry patterns (in the utero-placental vessels and middle cerebral artery), and maternal blood collection were performed before birth; cerebral ultrasound and neurologic examinations were performed after birth. S100B was higher (P <0.001) in IUGR pregnancies complicated by IVH than in those that were not and in controls. At a cutoff of 0.72 microg/L, sensitivity was 100% [95% confidence interval (95% CI), 87%-100%] and specificity was 99.3% (97.5%-99.9%) for prediction of IVH (area under the ROC curve, 0.999). The prevalence of IVH was 8.2% in the whole study population, 93% (95% CI, 83.6%-100%) in those with maternal S100B >0.72 microg/L, and 0% (0%-2.5%) in those with maternal S100B <0.72 microg/L. For prediction of IVH, measurements of maternal S100B may be useful at times before clinical, laboratory, and ultrasound patterns can identify risk of IVH.

S100B protects LAN‐5 neuroblastoma cells against Aβ amyloid‐induced neurotoxicity via RAGE engagement at low doses but increases Aβ amyloid neurotoxicity at high doses

At the concentrations normally found in the brain extracellular space the glial-derived protein, S100B, protects neurons against neurotoxic agents by interacting with the receptor for advanced glycation end products (RAGE). It is known that at relatively high concentrations S100B is neurotoxic causing neuronal death via excessive stimulation of RAGE. S100B is detected within senile plaques in Alzheimer's disease, where its role is unknown. The present study was undertaken to evaluate a putative neuroprotective role of S100B against Abeta amyloid-induced neurotoxicity. We treated LAN-5 neuroblastoma cultures with toxic amounts of Abeta25-35 amyloid peptide. Our results show that at nanomolar concentrations S100B protects cells against Abeta-mediated cytotoxicity, as assessed by 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and terminal deoxynucleotidyl transferase-mediated dUTP-fluorescein isothiocyanate nick end-labeling (TUNEL) experiments, by countering the Abeta-mediated decrease in the expression of the anti-apoptotic factor Bcl-2. This effect depends on S100B binding to RAGE because S100B is unable to contrast Abeta-mediated neurotoxicity in neurons overexpressing a signaling-deficient RAGE mutant lacking the cytosolic and transducing domain. Our data suggest that at nanomolar doses S100B counteracts Abeta peptide neurotoxicity in a RAGE-mediated manner. However, at micromolar doses S100B is toxic to LAN-5 cells and its toxicity adds to that of the Abeta peptide, suggesting that additional molecular mechanisms may be involved in the neurotoxic process.

Cerebrospinal Fluid S-100B Concentrations in Normal and Diseased Cattle

We measured the concentrations of S-100B, a marker protein used in humans to detect brain damage, in the cerebrospinal fluid (CSF) of clinically normal cattle (n=15, mean age +/- SD: 31.8 +/- 37.5 months) and of cattle with various inflammatory disorders (n=43, 70.6 +/- 31.9 months). The mean +/- SD CSF S-100B level was 2.9 +/- 1.6 ng/ml in the normal group and 7.0 +/- 7.4 ng/ml in the diseased group. Thirteen diseased cattle that had developed no obvious neurological signs showed abnormally high S-100B concentrations (> 8.0 ng/ml), whereas the two cattle with neurological disorders did not. No particular disease could be related to the S-100B rise. Therefore, it remains inconclusive whether measurement of CSF S-100B concentration is useful in veterinary neurological diagnosis.

Detection of S100B, S100A6 and galectin-3 ligands in meningiomas as markers of aggressiveness

The biological factors responsible for the increased aggressiveness in atypical meningiomas are not well known. The aim of this study is to evaluate the discriminatory value of a number of biological markers (S100 proteins and galectin-3 and its ligand profile) with respect to benign and atypical meningiomas. Using 63 meningiomas (39 benign and 24 atypical), we performed a semi-quantitative histochemical analysis of both the expression of galectin-3 and its ligand profile and the Ca2+-binding proteins S100A5, S100A6 and S100B. Three features were considered for each marker, namely the labeling index (LI), the staining intensity (SI) and the global score (LI + SI). A low S100A6 labeling index was observed in 51% of the benign and 25% of the atypical meningiomas (P=0.035). Furthermore, high S100B scores were observed in 46% of the benign and in only 8% of the atypical meningiomas (P=0.001). Seventy-one percent of the atypical meningiomas exhibited a low level of staining intensity for the galectin-3-binding sites as compared to only 36% of the benign meningiomas (P=0.007). The combination of these three markers (by means of a decision tree) enabled an improved discriminatory criterion to be established between the benign and the atypical meningiomas. Our results thus suggest that the galectin-3-binding sites and S100B (and S100A6 to a lesser extent) could play a role in the aggressiveness characterizing atypical meningiomas.

S100B serum levels and long-term improvement of negative symptoms in patients with schizophrenia.

S100B, a calcium-binding protein produced by astroglial cells, mediates paracrine and autocrine effects on neurons and glial cells. It regulates the balance between proliferation and differentiation in neurons and glial cells by affecting protective and apoptotic mechanisms. Post-mortem studies have demonstrated a deficit in synapses and dendrites in brains of schizophrenics. Recent studies have shown increased S100B levels in medicated acutely psychotic schizophrenic patients as well as unmedicated or drug naive schizophrenics. One study reported a positive correlation between negative symptoms and S100B. S100B serum levels (quantitative immunoassay) and psychopathology (Positive and Negative Syndrome Scale, PANSS) were examined upon study admission and after 12 and 24 weeks of standardized treatment in 98 chronic schizophrenic patients with primarily negative symptoms. Compared to age- and sex-matched healthy controls, the schizophrenic patients showed significantly increased S100B concentrations upon admission and after 12 and 24 weeks of treatment. High PANSS negative scores were correlated with high S100B levels. Regression analysis comparing psychopathology subscales and S100B identified negative symptomatology as the predicting factor for S100B. S100B is not just elevated during acute stages of disease since it remains elevated for at least 6 months following an acute exacerbation. With regard to psychopathology, negative symptomatology appears to be the predicting factor for the absolute S100B concentration. This might indicate that S100B in schizophrenic patients either promotes apoptotic mechanisms by itself or is released from astrocytes as part of an attempt to repair a degenerative or destructive process.