Cerebrospinal Fluid S100B Research Articles

Early prognostic factors in acute inflammatory demyelinating polyneuropathy: Role of neurofilaments

IntroductionGuillain-Barré syndrome (GBS) is an autoimmune disease that results in demyelination and axonal damage. Although the recovery is good in most patients, 20% remain significantly disabled.Neurofilament light chain (NfL) has been established as a biomarker of axonal damage in many diseases. MethodsWe measured NfL, S100B, and glial fibrillary acidic protein (GFAP) concentrations from blood and cerebrospinal fluid (CSF) taken upon admission from 19 patients with a history of GBS between January 2009 and December 2019 and investigated a correlation between them and clinical outcomes. ResultsAll patients fulfilled levels 1 or 2 of the Brighton diagnostic.Preceding infection was reported in 11 cases (58%).We classified 15 patients as acute inflammatory demyelinating polyneuropathy, 2 as AMAN, 1 as AMSAN, and 2 cases as Miller–Fisher syndrome.Five patients were transferred to an ICU, with a mean stay of 13 days. Functional outcome at 6 months after discharge was good in 12 patients (70.6%).We evaluated disease prognosis using the modified Erasmus GBS outcome score. The correlation was significant (p<.05) in the case of NfL in serum and CSF and GFAP in CSF (r=0.472 for serum NfL, 0.576 for CSF NfL, and 0.544 for CSF GFAP). ConclusionsWe confirm the finding of elevated levels of NfL, GFAP, and S100B in CSF and plasma in the acute phase of GBS.We can point out that their value has a certain relationship with the severity of the disease and prognosis, and that in some way, they have an influence, but we would lack more information to make good predictions.

Post-mortem utility of Neuron Specific Enolase (NSE) and Calcium Binding Protein B (S100B) for differentiating traumatic brain injury from other causes of death.

In forensic pathology, identifying causes of death in traumatic brain injuries (TBIs) devoid of observable signs presents a significant challenge. Post-mortem biochemistry plays a crucial role in forensic medicine, particularly in determining causes of death in TBIs that lack macroscopic or histopathological evidence. This study aimed to evaluate the utility of Neuron Specific Enolase (NSE) and S100 Calcium Binding Protein B (S100B) in post-mortem serum and cerebrospinal fluid (CSF) as markers for TBI. The relationship of these biochemical markers with survival time and post-mortem interval was also studied. The study sample consisted of 63 cases each from the TBI and the Non-TBI (NTBI) group. The NTBI group comprised of deaths due to mechanical asphyxia, myocardial infarction and isolated trunk trauma. While serum S100B and CSF NSE emerged as a promising marker for TBI, CSF S100B failed to differentiate TBI from the other causes of death. The absence of an association between the level of markers and survival time or post-mortem interval in TBIs highlights the limitations of these biomarkers in such contexts. This study underscores the potential of biochemical markers like serum S100B and CSF NSE in identifying TBI deaths, aiding forensic diagnoses where there are evidentiary limitations in traditional methods. Further research exploring additional markers and body fluids could enhance diagnostic precision in forensic neuropathology.

Search for cerebrospinal fluid biomarkers in patients with major psychiatric disorders: Multiplex immunoassay findings and proximity extension assay prospects.

Multiplex immunoassays have been developed to detect multiple proteins simultaneously and are used to search for biomarkers, including those present in major psychiatric disorders. This study aimed to review multiplex immunoassay studies on cerebrospinal fluid (CSF) biomarkers in patients with schizophrenia, bipolar disorder (BD), and major depressive disorder (MDD) and examine future research directions using improved proteomic techniques. According to the results of previous multiplex immunoassay studies, increased CSF IFN-β, IL-8, MCP-2, MMP-2, PAI-1, sICAM-1, and sVCAM-1 and decreased CSF ACE, APP, fibrinogen, and GDNF were observed in patients with schizophrenia, while CSF HGF and S100B were positively correlated with psychotic symptom and CSF IL-11, IL-29/IFN-λ1, and TSLP were negatively correlated. Increased CSF IFN-β and IL-1β and decreased CSF Aβ42, APP, IL-6, and NCAM-1 were observed, while CSF S100B was positively correlated with manic symptom in patients with BD. Increased CSF IL-4, MCP-1, MIP-1β, and MMP-2 were observed in patients with MDD, while CSF HGF and MMP-2 were positively correlated with depressive symptom and CSF IL-15 and MCP-1 were negatively correlated. However, signal cross-talk and cross-reactivity problems have been observed in previous studies using multiplex immunoassay. The proximity extension assay can be used to overcome cross-reactivity and enable ultrasensitive multiplexed detection and quantification of more than 1000 target proteins. However, proteomic studies using proximity extension assay technology in patients with schizophrenia, BD, or MDD are still scarce. Therefore, future high-quality proteomic studies are required to identify CSF biomarkers for larger sets of target proteins in patients with major psychiatric disorders.

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.

CD4 dim CD8 bright T cells are inversely associated with neuro-inflammatory markers among people with HIV.

HIV-associated neuroinflammation persists in the brain despite suppressive combination antiretroviral therapy (cART). We evaluated associations between a subset of CD8 + T cells, termed CD4 dim CD8 bright T cells, and soluble markers of immune activation and/or neuroinflammation in the cerebrospinal fluid (CSF) and plasma of people with HIV (PWH). Fifteen cART-naive PWH were enrolled and underwent blood draw, lumbar puncture for CSF collection, and neuropsychological tests at week 0 (pre-cART) and 24 weeks after cART initiation. CSF and peripheral blood T cells were evaluated with flow cytometry and soluble markers of immune activation were measured by multiplex and singleplex assays. Spearman bootstrap correlation coefficients with 10 000 resamples were computed and reported with corresponding 95% confidence intervals (CIs) for each marker of interest and T-cell type. The frequency of CSF CD4 dim CD8 bright T cells at week 0 was inversely related with CSF neopterin. In contrast, at week 24, CSF CD4 - CD8 + T cells were positively correlated with CSF s100β, a marker of brain injury. In the blood, at week 0, CD4 dim CD8 bright T cells were inversely correlated with MCP-1, IP-10, IL-8, IL-6, G-CSF, and APRIL and positively correlated with plasma RANTES and MMP1. At week 0, the frequency of blood CD4 - CD8 + were positively correlated with CRP and BAFF. CD4 dim CD8 bright T cells are associated with some anti-inflammatory properties, whereas CD4 - CD8 + T cells may contribute to inflammation and injury. Assessing the contrast between these two cell populations in neuroHIV may inform targeted therapeutic intervention to reduce neuroinflammation and associated neurocognitive impairment.

Serum and CSF brain damage markers NFL and GFAP correlate with tick-borne encephalitis disease severity - a multicenter study on Lithuanian and Swedish patients.

Our aim was to examine the correlation between biomarkers of neuronal and glial cell damage and severity of disease in patients with tick-borne encephalitis. One hundred and fifteen patients with tick-borne encephalitis diagnosed in Lithuania and Sweden were prospectively included, and CSF and serum samples obtained shortly after hospitalization. Using pre-defined criteria, cases were classified as mild, moderate, or severe TBE. Additionally, the presence of spinal nerve paralysis (myelitis) and/or cranial nerve affection were noted. Concentrations of brain cell biomarkers glial fibrillary acidic protein (GFAP), YKL40, S-100B, neurogranin, neurofilament light (NFL), and tau were analyzed in CSF, and in addition, NFL, GFAP and S-100B levels were measured in serum. The Jonckheere Terpstra test was used for group comparisons of continuous variables and Spearman's partial correlation test to adjust for age. CSF and serum concentrations of GFAP and NFL correlated with disease severity, independent of age, and with presence of nerve paralysis. The markers neurogranin, YKL40, tau and S-100B in CSF and S-100B in serum were detected, but their concentrations did not correlate with disease severity. Neuronal cell damage and astroglial cell activation with increased NFL and GFAP in CSF and serum were associated with a more severe disease, independent of age. Increased GFAP and NFL concentrations in CSF and NFL in serum were also indicative of spinal and/or cranial nerve damage. NFL and GFAP are promising prognostic biomarkers in TBE, and future studies should focus on determining the association between these biomarkers and long-term sequelae.

Assessment of selected inflammatory markers in bacterial and viral neuroinfections in children

Aim: The aim of the study was to assess the suggested biomarkers’ usefulness in diagnosing central nervous system infections in order to optimise treatment and minimise adverse outcomes. The study included a comprehensive comparison of the known parameters and a search for correlations with proposed biomarkers. Materials and methods: The data of 73 hospitalised children were reviewed. According to their final diagnoses, 42 participants were assigned to the control group, 13 to the cohort with bacterial and 18 to the cohort with viral neuroinfections. The children underwent clinically indicated blood and cerebrospinal fluid tests. The serum interleukin (IL)-1β, IL-6 and neopterin concentrations, and S100B protein and matrix metalloproteinase (MMP)-9 levels in the cerebrospinal fluid were determined. The results were compared between the groups and correlations were sought. Results: Serum IL-6 levels were found to have increased in viral (p = 0.0412) and bacterial (p &lt; 0.0001) infections, with a predominance of the latter (p = 0.0403). In terms of serum neopterin and IL-1β, the neuroinfection cohort did not differ from the control group. The level of S100B in the cerebrospinal fluid in bacterial disease was higher compared with the viral aetiology (p = 0.0325). The cerebrospinal fluid S100B correlated positively with serum IL-6 (p = 0.0138, R = 0.6396) and reversely with IgA and IgG levels (p = 0.0499, R = −0.5325; p = 0.0022, R = −0.7451, respectively) in the neuroinfection cohort. The cerebrospinal fluid MMP-9 was linked with cerebrospinal fluid cytosis in patients with viral (p = 0.0018, R = 0.7547) and bacterial (p = 0.0124, R = 0.6935) disease. The serum IL-6 levels correlated with IgA in the viral aetiology (p = 0.0374, R = 0.9). Conclusions: The MMP-9 level correlated with blood–brain barrier permeability, expressed by cerebrospinal fluid proteins and cytosis, which may indicate the possibility of sequelae. The higher serum concentrations of IL-6 and S100B in bacterial neuroinfections may reflect a more intense immune reaction associated with this aetiology.

Time-Dependent Changes in the Biofluid Levels of Neural Injury Markers in Severe Traumatic Brain Injury Patients-Cerebrospinal Fluid and Cerebral Microdialysates: A Longitudinal Prospective Pilot Study.

Monitoring protein biomarker levels in the cerebrospinal fluid (CSF) can help assess injury severity and outcome after traumatic brain injury (TBI). Determining injury-induced changes in the proteome of brain extracellular fluid (bECF) can more closely reflect changes in the brain parenchyma, but bECF is not routinely available. The aim of this pilot study was to compare time-dependent changes of S100 calcium-binding protein B (S100B), neuron-specific enolase (NSE), total Tau, and phosphorylated Tau (p-Tau) levels in matching CSF and bECF samples collected at 1, 3, and 5 days post-injury from severe TBI patients (n = 7; GCS 3-8) using microcapillary-based western analysis. We found that time-dependent changes in CSF and bECF levels were most pronounced for S100B and NSE, but there was substantial patient-to-patient variability. Importantly, the temporal pattern of biomarker changes in CSF and bECF samples showed similar trends. We also detected two different immunoreactive forms of S100B in both CSF and bECF samples, but the contribution of the different immunoreactive forms to total immunoreactivity varied from patient to patient and time point to time point. Our study is limited, but it illustrates the value of both quantitative and qualitative analysis of protein biomarkers and the importance of serial sampling for biofluid analysis after severe TBI.

Increased cerebrospinal fluid S100B protein levels in patients with trigeminal neuralgia and hemifacial spasm.

The pathophysiology of neurovascular compression syndrome has not been fully elucidated, and cerebrospinal fluid levels of nerve tissue-related markers involved in this disorder have not yet been reported. We measured cerebrospinal fluid levels of S100B protein, neuron-specific enolase, and myelin basic protein in 21 patients with trigeminal neuralgia, 9 patients with hemifacial spasms, and 10 patients with non-ruptured intracranial aneurysms (control). Cerebrospinal fluid levels of these markers were determined using commercially available assay kits. Both trigeminal neuralgia and hemifacial spasm groups showed significantly increased cerebrospinal fluid levels of S100B compared with the control group (1120 [IQR 391-1420], 766 [IQR 583-1500], and 255 [IQR 190-285] pg/mL, respectively; p = 0.001). There were no statistically significant differences in cerebrospinal fluid levels of neuron-specific enolase or myelin basic protein among the groups. Cerebrospinal fluid S100B levels were significantly higher in patients with trigeminal neuralgia and hemifacial spasm than in controls, which suggests the involvement of S100B in the underlying pathophysiology of neurovascular compression syndrome.

Longitudinal changes in brain glucose metabolism, astrocyte biomarkers and behavior in an APP/PS1 rat model

AbstractBackgroundImaging and fluid biomarkers have helped to reconceptualize Alzheimer’s Disease (AD) as a continuum. However, the biological interpretation of each AD biomarker remains under investigation. In this context, animal models that mimic the AD dynamic biomarkers cascade model present high translational value and can be used to refine our interpretation of biomarker findings. In light of this, we longitudinally evaluated [18F]FDG‐PET imaging, cerebrospinal fluid (CSF) glial and immune biomarkers, and behavior in the TgF344‐AD rat, a model harboring human APP/PS1 mutations.MethodsTgF344‐AD rats and wild‐type littermates were longitudinally evaluated at 3, 6, 9, and 12 months of age. Rats underwent [18F]FDG‐microPET scans, behavioral tasks (Y‐maze and novel objective recognition) and CSF samplings. The [18F]FDG SUVr was calculated with pons as the reference region. CSF glial and immune markers were measured by multiplex ELISA. A cross‐sectional cohort was used to measure cortical glutamate uptake (ex‐vivo slices) at the same time points. Further examination of astrocyte proteins immunocontent was conducted at 9 months of age.ResultsAt 3, 6 and 12 months, no changes in [18F]FDG metabolism were found. At 9 months of age, we identified a significant cortical hypermetabolism in the TgF344‐AD and a decline in alternance during the Y‐maze task. CSF GFAP levels were elevated at 6 and 9 months of age, while CSF S100B was decreased at 9 months of age. Additionally, the cortical and hippocampal glutamate uptake and GFAP cortical immunocontent were increased at 9 and 12 months of age. The recognition memory and CSF inflammatory markers (sTREM2, IL‐6, TNF‐α, IL‐10) were not altered in any of the ages evaluated.ConclusionOur results suggest that the TgF344‐AD rat model is suitable for studying astrocytic adaptations during early stages of amyloidosis in the rat brain. These adaptations include cortical glucose hypermetabolism, fluid biomarker evidence of reactive astrogliosis, and spatial memory impairment with concurrent abnormalities in astrocyte glutamate uptake in the cortex and hippocampus. Due to the critical role of astrocytes in brain glucose handling, our findings suggest that astrocyte reactivity could be driving glucose hypermetabolism and memory impairment early in the disease course.

Evaluation of the immediate effects of a single transcranial direct current stimulation session on astrocyte activation, inflammatory response, and pain threshold in naïve rats

Transcranial direct current stimulation (tDCS) has demonstrated clinical benefits such as analgesia, anti-inflammatory, and neuroprotective effects. However, the mechanisms of action of a single tDCS session are poorly characterized. The present study aimed to evaluate the effects of a single tDCS session on pain sensitivity, inflammatory parameters, and astrocyte activity in naive rats. In the first experiment, sixty-day-old male Wistar rats (n = 95) were tested for mechanical pain threshold (von Frey test). Afterward, animals were submitted to a single bimodal tDCS (0.5 mA, 20 min) or sham-tDCS session. According to the group, animals were re-tested at different time intervals (30, 60, 120 min, or 24 h) after the intervention, euthanized, and the cerebral cortex collected for biochemical analysis. A second experiment (n = 16) was performed using a similar protocol to test the hypotheses that S100B levels in the cerebrospinal fluid (CSF) are altered by tDCS. Elisa assay quantified the levels of tumor necrosis factor–alfa (TNF-α), interleukin-10 (IL10), S100 calcium-binding protein B (S100B), and Glial fibrillary acidic protein (GFAP). Data were analyzed using ANOVA and independent t-test (P < 0.05). Results showed that tDCS decreased pain sensitivity (30 and 60 min), cerebral TNF-α and S100B levels (30 min). CSF S100B levels increased 30 min after intervention. There were no differences in IL10 and GFAP levels. TCDS showed analgesic, anti-inflammatory, and neuroprotective effects in naive animals. Therefore, this non-invasive and inexpensive therapy may potentially be a preemptive alternative to reduce pain, inflammation, and neurodegeneration in situations where patients will undergo medical procedures (e.g., surgery).

Biomarkers of brain damage and inflammation in patients with acute cerebral ischemia

To study the pathogenetic and clinical significance of factors of hypoxic brain damage and inflammatory mediators in the development of stroke, to improve the diagnosis using laboratory markers of brain damage and inflammation in patients with acute cerebrovascular accident. We examined 55 people with stroke of the ischemic type at the age of 74 (67; 80) years, the comparison group consisted of 25 volunteers at the age of 65.0 (62.0; 66.5) years. Depending on the outcome of ischemic stroke, patients were assigned to the discharged group or to the deceased group. Blood serum and cerebrospinal fluid (CSF) S100b protein, glial fibrillar acidic protein and interleukin-6 (IL-6); blood serum neurospecific enolase, and cortisol and C-reactive protein (CRP) were determined. Clinical blood test and assessment of fibrinogen content were performed on days 1, 3 and 10 of stroke. There is an increase in the levels of markers of brain tissue damage and systemic inflammation in the blood and CSF in response to cerebral ischemia that reflects the synergy of these pathological processes in patients with stroke, their association with the severity of stroke and its outcome. The results indicate that the postischemic release of neurospecific proteins, an increase in the content of IL-6, CRP, and cortisol make it possible to additionally characterize the severity of stroke and the body's response to damage, and predict the outcome of the disease.

Amyloid-like deposits in the brain of transgenic mice overexpressing S100B protein.

S100 calcium-binding protein B (S100B) is a member of the S100 family, mainly expressed and secreted by astrocytes in the Central Nervous System. Extracellular levels of this protein have been used as a general marker of brain injury, particularly in blood serum and cerebrospinal fluid (CSF). Mice overexpressing S100B (S100BTg) was firstly developed to better understand the Down Syndrome and Alzheimer's Disease, once both S100B and amyloid precursor protein (APP) genes are located in chromosome 21. Also, it was previously demonstrated the exacerbation of amyloidogenesis in transgenic mice for both human APP and S100B, but the influence of this protein on APP processing had not yet been investigated in the S100BTg itself. Considering the interaction between the S100B protein and the amyloid beta processing, as well as the S100B's neuroinflammatory signalling, we investigated S100B and amyloid beta 42 peptide levels by Elisa in the hippocampus (Hp), frontal cortex (FC), hypothalamus (Ht), CSF, serum and also the possible amyloid deposition by Thioflavin-T and immunofluorescence in 1-year-old transgenic mice overexpressing S100B as Reeves' procedure, in female and male S100BTg and respective wild type (Wt) mice. Our results showed a higher S100B content in the three examined brain regions of S100BTg (Hp, FC and Ht) and Hp showed higher levels of this protein than other two regions, even in Wt. Moreover, for the first time we found elevated CSF S100B in these old transgenic mice, which supports the idea that S100B released by astrocytes could affect the neural neighborhood. In addition, we found more plaque-like deposits in males S100Tg than females in comparison with Wt. Ultimately, our data reinforces the importance and potential of this model for experimental studies and the role of S100B in the pathogenesis of AD, points out specific brain changes of S100B (in brain tissue and CSF) and indicates that changes in S100B and amyloid plaques in this mice seems to be dependent on sex.

Amyloid-β Processing in Aged S100B Transgenic Mice Is Sex Dependent.

(1) Background: Calcium-binding protein S100B is involved in neuroregeneration but has also been associated with neurodegeneration. These contrasting effects may result from concentration or duration of exposure. We investigated the effect of long-term increased S100B levels on amyloid-β processing in one-year-old transgenic (tg) mice with 12 copies of the murine S100B gene with specific consideration of sex and specific brain regions. (2) Methods: S100B and amyloid-β 42 (Aβ42) were quantified in serum, cerebrospinal fluid (CSF), adipose tissue, and different brain regions by ELISA in wild-type (wt) and S100Btg mice (each n = 7 per group). Thioflavin T (ThT) and Aβ immunostaining were performed for visualization of Aβ deposition. (3) Results: S100B in serum, CSF, and brain was significantly increased in S100Btg mice of both sexes. Aβ42 was significantly increased in the hippocampus of male S100Btg mice (p = 0.0075), and the frontal cortex of female S100Btg mice (p = 0.0262). ThT and Aβ immunostaining demonstrated Aβ deposition in different brain regions in S100Btg mice of both sexes and female wt. (4) Conclusion: Our data validate this experimental model for studying the role of S100B in neurodegeneration and indicate that Aβ processing is sex-dependent and brain region-specific, which deserves further investigation of signaling pathways and behavioral responses.

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.

Systematic Assessment of 10 Biomarker Candidates Focusing on α-Synuclein-Related Disorders.

Objective diagnostic biomarkers are needed to support a clinical diagnosis. To analyze markers in various neurodegenerative disorders to identify diagnostic biomarker candidates for mainly α-synuclein (aSyn)-related disorders (ASRD) in serum and/or cerebrospinal fluid (CSF). Upon initial testing of commercially available kits or published protocols for the quantification of the candidate markers, assays for the following were selected: total and phosphorylated aSyn (pS129aSyn), neurofilament light chain (NfL), phosphorylated neurofilament heavy chain (pNfH), tau protein (tau), ubiquitin C-terminal hydrolase L1 (UCHL-1), glial fibrillary acidic protein (GFAP), calcium-binding protein B (S100B), soluble triggering receptor expressed on myeloid cells 2 (sTREM-2), and chitinase-3-like protein 1 (YKL-40). The cohort comprised participants with Parkinson's disease (PD, n=151), multiple system atrophy (MSA, n=17), dementia with Lewy bodies (DLB, n=45), tau protein-related neurodegenerative disorders (n=80, comprising patients with progressive supranuclear palsy (PSP, n=38), corticobasal syndrome (CBS, n=16), Alzheimer's disease (AD, n=11), and frontotemporal degeneration/amyotrophic lateral sclerosis (FTD/ALS, n=15), as well as healthy controls (HC, n=20). Receiver operating curves (ROC) with area under the curves (AUC) are given for each marker. CSF total aSyn was decreased. NfL, pNfH, UCHL-1, GFAP, S100B, and sTREM-2 were increased in patients with neurodegenerative disease versus HC (P< 0.05). As expected, some of the markers were highest in AD (i.e., UCHL-1, GFAP, S100B, sTREM-2, YKL-40). Within ASRD, CSF NfL levels were higher in MSA than PD and DLB (P< 0.05). Comparing PD to HC, interesting serum markers were S100B (AUC: 0.86), sTREM2 (AUC: 0.87), and NfL (AUC: 0.78). CSF S100B and serum GFAP were highest in DLB. Levels of most marker candidates tested in serum and CSF significantly differed between disease groups and HC. In the stratification of PD versus other tau- or aSyn-related conditions, CSF NfL levels best discriminated PD and MSA. CSF S100B and serum GFAP best discriminated PD and DLB. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson Movement Disorder Society.

Increased Cerebrospinal Fluid S100B and NSE Reflect Neuronal and Glial Damage in Parkinson's Disease.

Introduction: The diagnosis of Parkinson’s disease (PD) mainly relies on clinical manifestation, but may be difficult to make in very early stages of the disease, especially in pre-motor PD. Thus, there is great interest in finding a biomarker for PD. Among diagnostic biomarkers, the most promising molecules are those which reflect the pathophysiological mechanisms of the disease. Until now, only α-synuclein, a classical CSF Alzheimer’s disease biomarker, and neurofilament light (NFL) chains have turned out to be helpful in differential diagnosis between PD and healthy control subjects.Aim: To assess whether CSF molecules related to some pathological processes present in PD might be of interest in the diagnosis of PD and whether they correlate with disease severity.Methods: CSF levels of S100B and neuron-specific enolase (NSE) were measured in 58 PD patients and in 28 healthy control subjects. Correlations were determined between the levels of these CSF molecules and measures of disease severity (Hoehn–Yahr scale and UPDRS part III), as well as disease duration and levodopa dose.Results: CSF S100B and CSF NSE were both significantly increased in PD subjects vs. healthy controls (p = 0.007 and p = 0.00035, respectively). CSF S100B was significantly positively correlated with measures of disease severity (H-Y score and UPDRS part III), as well as disease duration (p < 0.05). No correlation was found between CSF NSE levels and disease severity or disease duration (p > 0.05). CSF S100B levels alone provided a relatively high discrimination (AUC 0.77) between PD and healthy controls, with 60.7% sensitivity and 88.5% specificity (p < 0.001) at a cut-off value of 123.22 pg/ml. Similarly, CSF NSE levels alone provided a relatively high discrimination (AUC 0.775) between PD and healthy controls, with 78.6% sensitivity and 74.1% specificity at a cut-off value of 51.56 ng/ml (p < 0.001).Conclusions: Our results show that both CSF S100B and CSF NSE seem to be promising markers of the axonal and glial degeneration present in PD. Additionally CSF S100B may be a promising marker of PD progression.

Cerebrospinal fluid neuroplasticity-associated protein levels in patients with psychiatric disorders: a multiplex immunoassay study

To examine the role of neuroplasticity in the pathology of psychiatric disorders, we measured cerebrospinal fluid (CSF) neuroplasticity-associated protein levels. Participants were 94 patients with schizophrenia, 68 with bipolar disorder (BD), 104 with major depressive disorder (MDD), and 118 healthy controls, matched for age, sex, and ethnicity (Japanese). A multiplex immunoassay (22-plex assay) was performed to measure CSF neuroplasticity-associated protein levels. Among 22 proteins, 11 were successfully measured in the assay. CSF amyloid precursor protein (APP) and glial cell-derived neurotrophic factor (GDNF) levels were significantly lower in patients with schizophrenia, and CSF APP and neural cell adhesion molecule (NCAM)-1 levels were significantly lower in patients with BD, than in healthy controls (all p < 0.05). Positive and Negative Syndrome Scale total, positive, and general scores were significantly and positively correlated with CSF hepatocyte growth factor (HGF) (p < 0.01) and S100 calcium-binding protein B (S100B) (p < 0.05) levels in patients with schizophrenia. Young mania-rating scale score was significantly and positively correlated with CSF S100B level in patients with BD (p < 0.05). Hamilton Depression Rating Scale, core, sleep, activity, somatic anxiety, and delusion subscale scores were significantly and positively correlated with CSF HGF level, while sleep subscale score was positively correlated with CSF S100B and VEGF receptor 2 levels in patients with MDD (p < 0.05). Our results suggest that CSF APP, GDNF, and NCAM-1 levels are associated with psychiatric disorders, and that CSF HGF, S100B, and VEGF receptor 2 levels are related to psychiatric symptoms.

Altered Cerebral Blood Flow and Potential Neuroprotective Effect of Human Relaxin-2 (Serelaxin) During Hypoxia or Severe Hypovolemia in a Sheep Model.

Specific neuroprotective strategies to minimize cerebral damage caused by severe hypoxia or hypovolemia are lacking. Based on previous studies showing that relaxin-2/serelaxin increases cortical cerebral blood flow, we postulated that serelaxin might provide a neuroprotective effect. Therefore, we tested serelaxin in two emergency models: hypoxia was induced via inhalation of 5% oxygen and 95% nitrogen for 12 min; thereafter, the animals were reoxygenated. Hypovolemia was induced and maintained for 20 min by removal of 50% of the total blood volume; thereafter, the animals were retransfused. In each damage model, the serelaxin group received an intravenous injection of 30 µg/kg of serelaxin in saline, while control animals received saline only. Blood gases, shock index values, heart frequency, blood pressure, and renal blood flow showed almost no significant differences between control and treatment groups in both settings. However, serelaxin significantly blunted the increase of lactate during hypovolemia. Serelaxin treatment resulted in significantly elevated cortical cerebral blood flow (CBF) in both damage models, compared with the respective control groups. Measurements of the neuroproteins S100B and neuron-specific enolase in cerebrospinal fluid revealed a neuroprotective effect of serelaxin treatment in both hypoxic and hypovolemic animals, whereas in control animals, neuroproteins increased during the experiment. Western blotting showed the expression of relaxin receptors and indicated region-specific differences in relaxin receptor-mediated signaling in cortical and subcortical brain arterioles, respectively. Our findings support the hypothesis that serelaxin is a potential neuroprotectant during hypoxia and hypovolemia. Due to its preferential improvement of cortical CBF, serelaxin might reduce cognitive impairments associated with these emergencies.

Neuroinflammatory markers associate with cognitive decline after major surgery: Findings of an explorative study.

Long-term cognitive decline is an adverse outcome after major surgery associated with increased risk for mortality and morbidity. We studied the cerebrospinal fluid (CSF) and serum biochemical inflammatory response to a standardized orthopedic surgical procedure and the possible association with long-term changes in cognitive function. We hypothesized that the CSF inflammatory response pattern after surgery would differ in patients having long-term cognitive decline defined as a composite cognitive z score of ≥1.0 compared to patients without long-term cognitive decline at 3 months postsurgery. Serum and CSF biomarkers of inflammation and blood-brain barrier (BBB) integrity were measured preoperatively and up to 48 hours postoperatively, and cognitive function was assessed preoperatively and at 2 to 5 days and 3 months postoperatively. Surgery was associated with a pronounced increase in inflammatory biomarkers in both CSF and blood throughout the 48-hour study period. A principal component (PC) analysis was performed on 52 inflammatory biomarkers. The 2 first PC (PC1 and PC2) construct outcome variables on CSF biomarkers were significantly associated with long-term cognitive decline at 3 months, but none of the PC construct serum variables showed a significant association with long-term cognitive decline at 3 months. Patients both with and patients without long-term cognitive decline showed early transient increases of the astroglial biomarkers S-100B and glial fibrillary acidic protein in CSF, and in BBB permeability (CSF/serum albumin ratio). Surgery rapidly triggers a temporal neuroinflammatory response closely associated with long-term cognitive outcome postsurgery. The findings of this explorative study require validation in a larger surgical patient cohort. Ann Neurol 2020;87:370-382.