Cerebrospinal Fluid S100B Concentrations Research Articles

Associations of physical activity with cerebrospinal fluid biomarkers of neurodegeneration, neuroinflammation, and Alzheimer’s disease

AbstractBackgroundAlzheimer’s disease (AD) and related dementias are public health concerns often with long preclinical phases. Thus, intervention and prevention methods in midlife could prove efficacious. Cerebrospinal fluid (CSF) biomarkers can change early in the disease process and have been utilized for dementia diagnostics. Multiple health‐related lifestyle factors have been associated with risk for AD, yet existing research on lifestyle factors has focused on clinical outcomes such as cognitive decline, mild cognitive impairment and/or AD dementia; their associations with early changes in CSF are less understood. Our aim was to determine whether physical activity (PA), a modifiable lifestyle factor, is associated with biomarkers for neurodegeneration, glial activation, and inflammation.MethodParticipants were N = 204 cognitively unimpaired adults (aged 45–80 years) from the Wisconsin Registry for Alzheimer’s Prevention and the Wisconsin Alzheimer’s Disease Research Center, two on‐going, longitudinal studies of preclinical AD. PA was defined as the weekly metabolic equivalent (MET), calculated by scoring amount and intensity of mild, moderate, and vigorous exercises per week (range 0–79 METS). We assessed CSF biomarkers using robust exploratory prototype assays from the NeuroToolKit research platform (Roche Diagnostics International, Switzerland). Participants also completed demographic and health questionnaires (Table 1). We used linear regression models to assess associations between PA and CSF biomarkers, adjusting for age at biomarker assessment, sex, education, and chronic health conditions (diabetes, hypertension, cardiovascular disease).ResultPreliminary results showed that participants who engage in more PA had higher CSF S100B concentrations, a pro‐inflammatory calcium‐binding protein (standardized b change per MET = 0.0013, 95% confidence interval: 0.0003–0.0023; p = .01). No other PA‐biomarker associations were significant.ConclusionHigher PA was significantly associated with higher CSF concentration of S100B, a marker of (astro‐)glial activation. Future studies will need to examine whether PA is associated with higher S100B in individuals along the disease continuum of AD, and whether this is reflected in the blood. Longer follow‐ups may be needed to determine associations of PA with other biomarkers, where we had limited variation in this primarily healthy study cohort.

Elevated neuron-specific enolase and S100 calcium-binding protein B concentrations in cerebrospinal fluid of patients with anti-N-methyl-d-aspartate receptor encephalitis

BackgroundAnti‑N‑methyl‑d‑aspartate receptor (NMDAR) encephalitis is a relatively common autoimmune neurological disease of the central nervous system (CNS). Neuron-specific enolase (NSE) and S100 calcium-binding protein B (S100B) are structural proteins of the central nervous system (CNS). In patients with CNS injury accompanied by nervous tissue and cellular damage, these structural proteins are released from cells; their extracellular concentrations, including those in cerebrospinal fluid (CSF) and blood, subsequently increase. MethodsThirty-six patients with anti-NMDAR encephalitis were prospectively recruited. The CSF NSE and S100B concentrations were measured in 19 and 17 patients, respectively. The CSF NSE and S100B concentrations were measured in 21 patients with noninflammatory neurological disease as controls. All measurements were performed using enzyme-linked immunosorbent assays. ResultsThe CSF NSE and S100B concentrations were remarkably higher in the patients with anti-NMDAR encephalitis than in the controls. The early NSE or S100B concentrations in CSF were associated with the mRS. ConclusionCSF NSE and S100B concentration in patients with anti-NMDAR encephalitis is higher than in patients with non-inflammatory neurological disease. The early NSE or S100B concentrations in CSF were associated with the mRS and we can use it to determine the prognosis of the disease.

Early CSF and Serum S100B Concentrations for Outcome Prediction in Traumatic Brain Injury and Subarachnoid Hemorrhage

ObjectivesS100B has been proposed as a putative biochemical marker in determining the extent of brain injury and corresponding prognosis in neurotrauma. The aim of this study was to evaluate the prognostic value of S100B early concentrations in serum and cerebrospinal fluid (CSF) in traumatic brain injury (TBI) and subarachnoid hemorrhage (SAH), to determine prognostically relevant threshold values and to evaluate fluctuation following EVD placement. Patients and methodsIn 102 patients (45 SAH and 57 TBI) under intensive care unit (ICU) treated between January 2011 and December 2012 with external ventricular drain (EVD) S100B measurements were performed simultaneously in serum and CSF during the first 5 days and before and after EVD exchange. Glasgow coma scale (GCS) was assessed on admission and Glasgow outcome scale (GOS) 6 months later. ResultsPeak S100B levels in CSF and serum were measured on the first day after admission and concentrations decreased during the ensuing days post injury gradually. CSF and serum S100B concentrations in TBI patients were significantly higher than in SAH (p<0.005). Both in TBI and SAH patients S100B concentrations in CSF and serum were significantly higher in patients with an unfavorable outcome (GOS 1–3) in comparison to patients with a good outcome (GOS 4–5). Correlation of S100B concentrations in serum and GOS score at 6 months was significant both in TBI and SAH (p<0.05). Serum S100B concentrations >0.7μg/l correlated with 100% mortality. Correlation between S100B in CSF and GOS was significant in SAH (p<0.05), whereas it was not significant in TBI.After EVD exchange (n=53) we found a significant increase of S100B concentration in CSF (p<0.005). ConclusionInitial S100B levels have a limited prognostic value in neurotrauma with CSF concentrations being highly sensitive to smallest influences like EVD placement. However, high initial S100B levels of >0.7μg/dl in serum are associated with 100% mortality, which might help to guide therapy strategies in severe neurotrauma.

S100B in the cerebrospinal fluid—A marker for glial damage in the rabbit model of pneumococcal meningitis

The rabbit model provides an important experimental setting for the evaluation of antibiotic agents against pneumococcal meningitis. One of the primary targets of this model is the study of neuronal and glial cell damage in bacterial meningitis. The aim of this investigation was to evaluate whether a significant increase of S100B in the cerebrospinal fluid (CSF) as an indicator of white matter damage could be observed in this meningitis model. Seven rabbits were infected intracisternally with S. pneumoniae, and CSF S100B concentrations were examined serially before infection, at 12 h, 14 h, 17 h, 20 h, and at 24 h after infection. The course of CSF S100B increase and its relation to other parameters of brain tissue destruction and CSF inflammation were measured. Axonal damage was visualized by amyloid precursor protein (APP) immunostaining and demyelination by Luxol Fast Blue/Periodic Acid Schiff (LFB-PAS) stain. In each animal, we observed a distinct rise in S100B concentration in the CSF due to pneumococcal meningitis. We conclude that the CSF concentration of the glial S100B protein can be used as an additional parameter for future interventional studies focusing on glial cell damage in the rabbit model of bacterial meningitis.

No neurochemical evidence for brain injury caused by heading in soccer

Background:The possible injurious effect to the brain of heading in soccer is a matter of discussion.Objective:To determine whether standardised headings in soccer are associated with increased levels of biochemical markers...

Serum and cerebrospinal fluid S100B concentrations in patients with neurocysticercosis

The clinical manifestations of neurocysticercosis (NC) are varied and depend on the number and location of cysts, as well as on the host immune response. Symptoms usually occur in NC when cysticerci enter a degenerative course associated with an inflammatory response. The expression of brain damage markers may be expected to increase during this phase. S100B is a calcium-binding protein produced and released predominantly by astrocytes that has been used as a marker of reactive gliosis and astrocytic death in many pathological conditions. The aim of the present study was to investigate the levels of S100B in patients in different phases of NC evolution. Cerebrospinal fluid and serum S100B concentrations were measured in 25 patients with NC: 14 patients with degenerative cysts (D), 8 patients with viable cysts (V) and 3 patients with inactive cysts. All NC patients, except 1, had five or less cysts. In most of them, symptoms had been present for at least 1 month before sample collection. Samples from 8 normal controls (C) were also assayed. The albumin quotient was used to estimate the blood-brain barrier permeability. There were no significant differences in serum (P = 0.5) or cerebrospinal fluid (P = 0.91) S100B levels among the V, D, and C groups. These findings suggest that parenchymal changes associated with a relatively small number of degenerating cysts probably have a negligible impact on glial tissue.

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.

Changes in CSF S100B and cytokine concentrations in early-phase severe traumatic brain injury.

S100B protein (S100B) has been described as a marker of brain injury. Various cytokines also increase in the cerebrospinal fluid (CSF) of patients with severe traumatic brain injury (TBI). Thus, we investigated early changes in the concentrations of CSF S100B and various cytokines after TBI and evaluated the relations of both S100B and cytokines to intracranial pressure (ICP) and prognosis. Twenty-three patients with severe TBI and a Glasgow Coma Scale score of 8 or less on admission were included in this study. CSF and serum samples were obtained on admission and at 6, 12, 24, 48, 72, and 96 h after injury. CSF concentrations of S100B and CSF and serum concentrations of five cytokines (IL-1beta, TNF-alpha, IL-6, IL-8, and IL-10) were measured and compared. The CSF S100B concentration was increased for 6 h after injury and decreased thereafter. The CSF concentrations of IL-6 and IL-8 peaked within 6 h after injury; other cytokines (IL-1beta, TNF-alpha, and IL-10) were elevated for 24 h after injury and gradually decreased thereafter. Peak CSF S100B concentrations correlated significantly with ICP determined at the time CSF samples were taken (r = 0.729, P < 0.0001). For the cytokines investigated, only the peak CSF IL-1beta concentration correlated significantly and positively with the peak CSF S100B concentration (r = 0.397, P < 0.005). Peak CSF concentrations of S100B (1649 +/- 415 microg/L, mean +/- SEM) and IL-1beta (16.5 +/- 3.3 pg/mL) in the 6 patients with high ICP were significantly higher than those (233 +/- 67 microg/L, 7.6 +/- 1.7 pg/mL, respectively) in the 17 patients with low ICP (P < 0.05). The CSF S100B concentration (1231 +/- 378 microg/L) in eight patients with an unfavorable outcome was significantly higher than that (267 +/- 108 microg/L) in 15 patients with a favorable outcome (P < 0.05). The CSF IL-1beta concentration (14.8 +/- 3.4 pg/mL) in eight patients with an unfavorable outcome tended to be higher than that (7.3 +/- 1.5 pg/mL) in 15 patients with a favorable outcome (P = 0.057). CSF concentrations of S100B and cytokines peak within 24 h after severe TBI and decrease gradually thereafter. CSF S100B and IL-1beta may be useful as predictors of outcome in cases of severe TBI.

Increased S100B in cerebrospinal fluid of infants with bacterial meningitis: relationship to brain damage and routine cerebrospinal fluid findings.

Perinatal infections such as bacterial meningitis (BM) are one of the major factors associated with perinatal brain damage (1)(2)(3)(4). Despite accurate monitoring, the early stages of meningitis are crucial because brain damage may occur at a subclinical stage when ultrasound assessment is still silent (5)(6). Laboratory assessment is based on chemical analysis of cerebrospinal fluid (CSF) and the detection of bacteria, and the possibility of detecting cases at risk of brain damage is to date limited. The measurement of brain constituents able to diagnose subclinical lesions at this stage could therefore be useful. S100B is a calcium-binding protein primarily present in nervous tissue (7)(8)(9). Increased S100B in biological fluids has been shown to be a marker of brain damage both in adults and during the antenatal and postnatal periods (10)(11)(12)(13)(14)(15)(16). The present case–control study is aimed at investigating whether the measurement of S100B in CSF could also be useful in infants with BM for the early detection of cases at risk of encephalitis. Samples of CSF were collected from infants consecutively admitted between April 1998 and June 2000 to our tertiary referral center for intensive care for infectious diseases. For the present study we identified from our database 44 patients with BM and matched them for gestational age at sampling with 44 patients without BM (1 BM case vs 1 control). We retrieved clinical, laboratory, and routine CSF test data and CSF S100B concentrations. Eligibility criteria for infants with BM were as follows: clinical (respiratory distress, lethargy, presence/absence of minor/major neurologic symptoms, feeding and abdominal distension problems, temperature instability or increases, unexplained recurrent hypoglycemia, poor vascular perfusion) and laboratory signs of septicemia with altered CSF …

Serum S100B in pregnancy-related hypertensive disorders: a case-control study.

Eclampsia is defined as the occurrence of seizures and/or coma resulting from hypertensive encephalopathy on a background of preeclampsia (1). Eclampsia appears to be caused by a failure of the brain’s autoregulatory response to increases in blood pressure, leading to an increase in cerebral perfusion pressure with overperfusion injury similar to that observed in hypertensive encephalopathy (2)(3). Brain edema and hemorrhage ensue, as observed in imaging studies (4)(5), and there is evidence to suggest that these alterations can cause ischemia to brain cells. These events lead to neurologic symptoms (6), including seizures as well as cortical blindness, aphasia, limb weakness, psychosis, coma, and cerebrovascular accidents. Studies have analyzed various diagnostic methods, such as transcranial Doppler measurements, as a way to evaluate neurologic involvement in preeclampsia (3)(7). To date, however, there is no reliable laboratory marker to identify patients at risk for eclampsia or its related complications. S100B is a 21-kDa protein physiologically produced and released primarily by astrocytes in the central nervous system (CNS), where it exerts neurotrophic and gliotrophic actions (8). Because ∼95% of S100B is located in the CNS, the results of several studies have suggested that an increase in S100B in blood and cerebrospinal fluid could be a potential marker of neural injury, indicating reactive gliosis, astrocytic death, and/or blood–brain barrier dysfunction. Accordingly, increased S100B concentrations in cerebrospinal fluid and/or blood have been reported in several pathologic conditions causing acute and chronic brain injury, such as head trauma (9), stroke (10), schizophrenia (11), and human T-lymphotropic virus type 1-associated myelopathy (12). Some studies have also evaluated S100B as a marker of recent seizures. Although S100B has been shown to be increased in both cerebrospinal fluid and brain tissue of patients with temporal lobe epilepsy (13)(14), studies in which …

Cerebrospinal fluid S100B correlates with brain atrophy in Alzheimer's disease

S100B is a predominantly astrocytic protein with dose-dependent cytotoxic and neurotrophic properties encoded on chromosome 21q22.3. Concentrations of S100B were measured in the cerebrospinal fluid (CSF) of 31 patients with Alzheimer's disease (AD), 36 patients with frontotemporal lobe dementia (FTLD) and 49 patients with other non-inflammatory neurological diseases. Additional CSF S100B concentrations were correlated with normalised brain volume measurements in AD and FTLD. CSF S100B was significantly higher in AD (Mean±standard deviation=0.4±0.2 ng/ml) and FTLD (0.42±0.19 ng/ml) patients when compared with control subjects (0.25±0.08, P<0.001). In patients with AD, S100B correlated negatively with normalised brain volume ( R S=−0.53, P<0.001). No such correlation was found for FTLD patients. This study supports the concept that S100B is of pathological relevance for degeneration of the central nervous system in AD.

The Serum S100B Concentration Is Age Dependent

S100B is a 21-kDa calcium-binding protein produced and released primarily by astrocytes in the central nervous system (CNS), where it exerts neurotropic and gliotropic actions (1). Several studies have investigated the potential role of S100B as a peripheral biochemical marker of neural injury, including reactive gliosis, astrocytic death, and/or blood-brain barrier dysfunction (2). Increased cerebrospinal fluid (CSF) and/or serum S100B has been reported in several acute and chronic injuries, including traumatic brain injury (3), stroke (4), Alzheimer disease (5), schizophrenia (6), HTLV-I-associated myelopathy (7), and systemic lupus erythematosus (8). Previous neurodevelopmental studies have demonstrated age-related changes in S100B tissue expression and distribution in the CNS in mammals, which may be related to the different roles of this protein in distinct brain regions during the fetal period, adulthood, and aging (1)(9). Furthermore, S100B concentrations in CSF have been noted to increase with age in healthy individuals (10). Because these increases are more evident in men than women (11), S100B concentrations in CSF may be sex and age dependent, suggesting that age- and sex-matched controls may be necessary for studies of S100B in CSF. To determine the usual concentrations for plasma S100B in adults, Wiesmann et al. (12) measured the protein in healthy blood donors and found no differences with sex and age in individuals 18–65 years of age, in agreement with our findings in previous studies in adults (6)(7)(8). To our knowledge, however, S100B concentrations in blood in childhood and adolescence were not established until recently. The present study was performed to verify S100B serum concentrations in healthy individuals of different ages, ranging from neonates to adults. We collected blood samples from 19 healthy term neonates (<48 h of age) and from 25 healthy children 4–16 years of age undergoing routine clinical and …

Cerebrospinal fluid S100B is elevated in the earlier stages of Alzheimer's disease

Postmortem demonstration of increased expression of biologically active S100B in Alzheimer's disease (AD) and its relation to progression of neuropathological changes across the cortical regions suggests involvement of this astrocytic cytokine in the pathophysiology of AD. The hypothesis that the overexpression of S100B in Alzheimer brain is related to the progression of clinical symptoms was addressed in living persons by measuring S100B concentrations in cerebrospinal fluid (CSF) from AD patients with a broad range of clinical dementia severity and from healthy older persons. The effect of normal aging on CSF S100B concentrations also was estimated. CSF S100B did not differ between all 68 AD subjects (0.98±0.09 ng/ml (mean±S.E.M.)) and 25 healthy older subjects (0.81±0.13 ng/ml). When AD subjects were divided into mild/moderate stage and advanced stage clinical dementia severity by the established Clinical Dementia Rating Scale (CDR) criteria, S100B was significantly higher in the 46 mild/moderate stage AD subjects (1.17±0.11 ng/ml) than in either the 22 advanced stage AD subjects (0.60±0.12 ng/ml) or the healthy older subjects. Consistent with higher CSF S100B in mild to moderate AD, there was a significant correlation among all AD subjects between CSF S100B and cognitive status as measured by the Mini Mental State Exam (MMSE) score. CSF S100B did not differ between healthy older subjects and healthy young subjects. These results suggest increased CNS expression of S100B in the earlier stages of AD, and are consistent with a role for S100B in the initiation and/or facilitation of neuritic plaque formation in AD brain.

A specific and sensitive ELISA for measuring S-100b in cerebrospinal fluid

A sensitive, simple and specific sandwich ELISA for S-100b is described. This method involves the binding of a monoclonal anti-S-100b antibody to the wall of a microtitre plate. This capture antibody is subsequently incubated with S-100b standard, control or patient sample in the form of cerebrospinal fluid (CSF). After incubation, the microtitre plate is washed and horseradish peroxidase-labelled polyclonal anti-S-100b is added (detector antibody). The amount of detector antibody bound to the microtitre plate is proportional to the amount of S-100b in the sample. The assay has a lower limit of detection of 0.04 ng/ml and shows <0.006% reactivity with the closely related polypeptide S-100a. The assay has a mean within-batch precision of 9.3 and 5.6% at S-100b concentrations of 0.38 and 0.8 ng/ml, respectively. The between batch precision is 8.9 and 8.1% at S-100b concentrations of 0.12 and 0.34 ng/ml, respectively. The recovery of S-100b from CSF spiked with 0.5 ng/ml was 94% with a CV of 8.5%. The assay may be completed in less than 5 h using precoated microtitre plates, thus lending itself to routine use in clinical laboratories. Using this ELISA, 154 CSF samples were analysed and 19% of samples were found to have elevated levels. The highest levels were found in patients with cerebral haemorrhage or central nervous system malignancy. S-100b concentrations from individuals without evidence of neurological disease were found to be less than 0.4 ng/ml. Only 5% of patients with multiple sclerosis were found to have elevated CSF S-100b concentrations. Serial CSF samples taken from a patient with an infected in-dwelling shunt showed a dramatic decline, suggesting that S-100b is rapidly cleared.