Syntaxin-1a and SNAP-25 Expression Level is Increased in the Blood Samples of Ischemic Stroke Patients.

Abstract The interest in peripheral blood biomarkers is growing exponentially in several neurological disorders including Ischemic Stroke (IS). The identification of neurological biochemical signs through blood sample analyses would be revolutionary allowing a better pathology diagnosis giving also information on potential recovery after specific treatments. Indeed, the increased permeability of the blood-brain barrier, following a brain infarct, allows the detection of synaptic proteins in the blood flow. In this work, we analyzed the expression levels of two synaptic proteins belonging to the Soluble N-ethylmaleimide-Sensitive Fusion Protein Attachment Protein Receptor (SNARE) family, Syntaxin (STX)-1a and Synaptosomal Associated Protein, 25 kDa (SNAP-25), in Peripheral Blood Mononuclear Cell (PBMC), serum and in Neuronal Derived Extracellular vesicles (NDEs) of IS patients, age and sex matched healthy control (HC) and younger HC (Y-HC). Interestingly, we found, for the first time, that STX-1a protein is present in the cytoplasm of PBMC. Moreover, both protein, STX-1a and SNAP-25, levels were significantly augmented in all IS patient’s blood fractions (serum, PBMCs and NDEs) compared to control subjects. Interestingly, the STX-1a blood levels always correlated with the IS clinical scales National Institutes of Health Stroke Scale (NIH-SS) and the modified Barthel Index (BI). These results prompted us to speculate that STX-1a and SNAP-25 hematic fluctuations depict the brain damage after an ischemic attack and that their hematic detection could represent a novel and accessible IS biomarkers.

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Reduced mRNA Expression of PTGDS in Peripheral Blood Mononuclear Cells of Rapid-Cycling Bipolar Disorder Patients Compared with Healthy Control Subjects

The International Journal of Neuropsychopharmacology ◽

10.1093/ijnp/pyu101 ◽

2014 ◽

Vol 18 (5) ◽

pp. pyu101-pyu101 ◽

Cited By ~ 11

Author(s):

K. Munkholm ◽

L. Peijs ◽

L. V. Kessing ◽

M. Vinberg

Keyword(s):

Bipolar Disorder ◽

Mrna Expression ◽

Peripheral Blood Mononuclear Cells ◽

Peripheral Blood ◽

Mononuclear Cells ◽

Rapid Cycling ◽

Peripheral Blood Mononuclear ◽

Control Subjects ◽

Blood Mononuclear Cells ◽

Healthy Control

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Brain-derived neurotrophic factor in peripheral blood mononuclear cells and stroke outcome

Experimental Biology and Medicine ◽

10.1177/1535370218815612 ◽

2018 ◽

Vol 243 (15-16) ◽

pp. 1207-1211 ◽

Cited By ~ 1

Author(s):

Martin Pedard ◽

Céline Brenière ◽

Nicolas Pernet ◽

Catherine Vergely ◽

Yannick Béjot ◽

...

Keyword(s):

Ischemic Stroke ◽

Functional Outcome ◽

Peripheral Blood Mononuclear Cells ◽

Peripheral Blood ◽

Mononuclear Cells ◽

Stroke Outcome ◽

Stroke Patients ◽

Peripheral Blood Mononuclear ◽

Ischemic Brain ◽

Blood Mononuclear Cells

Stroke outcome is dependent on brain-derived neurotrophic factor (BDNF)-dependent neuroplasticity. As peripheral blood mononuclear cells (PBMC) contain BDNF, diapedesis of these cells might be followed by BDNF delivery to the ischemic brain. To test this hypothesis, we investigated the association between BDNF levels in PBMC and functional outcome in patients with ischemic stroke. BDNF was measured in PBMC that were isolated from ischemic stroke patients ( n = 40) just before (day 0) and after (days 1 and 3) fibrinolysis. Three months after stroke, patients were stratified using the modified Rankin Scale (mRS) according to the unfavorable (mRS scores 3–6) and favorable (mRS scores 0–2) functional outcome. We used univariate and multivariate logistic regressions to assess the relationship between BDNF levels in PBMC and functional outcome. BDNF levels in PBMC decreased from day 0 to day 3 in patients with unfavorable outcome, while they remained stable in patients with favorable outcome. Patients with favorable outcome exhibited at day 3 higher PBMC-BDNF levels than patients with unfavorable outcome and the levels were associated with good outcome (odd ratio: 12.0; 95% confidence interval, 1.4–106.2, P = 0.023). PBMC-BDNF levels remained a predictor of stroke outcome after adjusting from cardiovascular risk, interval between admission and fibrinolysis, stroke severity from hospital admission to discharge, lymphocytes count, neutrophils/lymphocytes ratio at admission. Favorable functional outcome in ischemic stroke patients that benefited from fibrinolysis was predicted by a high BDNF level in PBMC, suggesting that PBMC might serve as a cellular vector to deliver BDNF to the ischemic brain. Impact statement There are a great number of arguments suggesting that BDNF could be involved in stroke recovery dependent of neuroplasticity. Methods that can enhance BDNF levels in the ischemic brain could therefore have great clinical value. Peripheral blood mononuclear cells (PBMC) that contain BDNF and infiltrate early and sustainably the ischemic brain might be used as a cellular vector to deliver BDNF to the ischemic brain and consequently promote recovery. This work is important in this field to show if this BDNF derived from BDNF could exert a positive action on stroke recovery. Our main results showed that a high BDNF level at day 3 after hospital admission was associated with a 12.4 fold increase in favorable outcome after adjusting for still recognized prognostic markers. The new information in this field is this finding identifies PBMC as an attractive cellular vector to deliver BDNF to the ischemic brain.

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Gene expression in human peripheral blood mononuclear cells upon acute ischemic stroke

Journal of Neurology ◽

10.1007/s00415-008-0784-z ◽

2008 ◽

Vol 255 (5) ◽

pp. 723-731 ◽

Cited By ~ 38

Author(s):

C. Grond-Ginsbach ◽

M. Hummel ◽

T. Wiest ◽

S. Horstmann ◽

K. Pfleger ◽

...

Keyword(s):

Gene Expression ◽

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Peripheral Blood Mononuclear Cells ◽

Peripheral Blood ◽

Mononuclear Cells ◽

Human Peripheral Blood ◽

Peripheral Blood Mononuclear ◽

Blood Mononuclear Cells

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Peripheral Blood Mononuclear Cell Metabolism Acutely Adapted to Postprandial Transition and Mainly Reflected Metabolic Adipose Tissue Adaptations to a High-Fat Diet in Minipigs

Nutrients ◽

10.3390/nu10111816 ◽

2018 ◽

Vol 10 (11) ◽

pp. 1816 ◽

Cited By ~ 5

Author(s):

Yuchun Zeng ◽

Jérémie David ◽

Didier Rémond ◽

Dominique Dardevet ◽

Isabelle Savary-Auzeloux ◽

...

Keyword(s):

Adipose Tissue ◽

Peripheral Blood ◽

Time Course ◽

Mononuclear Cells ◽

Cell Metabolism ◽

Whole Body ◽

High Fat ◽

Short Term ◽

Peripheral Blood Mononuclear ◽

First Time

Although peripheral blood mononuclear cells (PBMCs) are widely used as a valuable tool able to provide biomarkers of health and diseases, little is known about PBMC functional (biochemistry-based) metabolism, particularly following short-term nutritional challenges. In the present study, the metabolic capacity of minipig PBMCs to respond to nutritional challenges was explored at the biochemical and molecular levels. The changes observed in enzyme activities following a control test meal revealed that PBMC metabolism is highly reactive to the arrival of nutrients and hormones in the circulation. The consumption, for the first time, of a high fat–high sucrose (HFHS) meal delayed or sharply reduced most of the observed postprandial metabolic features. In a second experiment, minipigs were subjected to two-month HFHS feeding. The time-course follow-up of metabolic changes in PBMCs showed that most of the adaptations to the new diet took place during the first week. By comparing metabolic (biochemical and molecular) PMBC profiles to those of the liver, skeletal muscle, and adipose tissue, we concluded that although PBMCs conserved common features with all of them, their response to the HFHS diet was closely related to that of the adipose tissue. As a whole, our results show that PBMC metabolism, particularly during short-term (postprandial) challenges, could be used to evaluate the whole-body metabolic status of an individual. This could be particularly interesting for early diagnosis of metabolic disease installation, when fasting clinical analyses fail to diagnose the path towards the pathology.

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Peripheral Blood Mononuclear Cell Proteome Changes in Patients with Myelodysplastic Syndrome

BioMed Research International ◽

10.1155/2015/872983 ◽

2015 ◽

Vol 2015 ◽

pp. 1-17 ◽

Cited By ~ 2

Author(s):

Klara Pecankova ◽

Pavel Majek ◽

Jaroslav Cermak ◽

Jan E. Dyr

Keyword(s):

Peripheral Blood ◽

Mononuclear Cells ◽

Expression Profiles ◽

Peripheral Blood Mononuclear ◽

Sds Page ◽

Proteome Changes ◽

Protein Alterations ◽

Cell Proteome ◽

First Time ◽

Proteasome Protein

Our aim was to search for proteome changes in peripheral blood mononuclear cells (PBMCs) of MDS patients with refractory cytopenia with multilineage dysplasia. PBMCs were isolated from a total of 12 blood samples using a Histopaque-1077 solution. The proteins were fractioned, separated by 2D SDS-PAGE (pI 4–7), and double-stained. The proteomes were compared and statistically processed with Progenesis SameSpots; then proteins were identified by nano-LC-MS/MS. Protein functional association and expression profiles were analyzed using the EnrichNet application and Progenesis SameSpots hierarchical clustering software, respectively. By comparing the cytosolic, membrane, and nuclear fractions of the two groups, 178 significantly (P<0.05, ANOVA) differing spots were found, corresponding to 139 unique proteins. Data mining of the Reactome and KEGG databases using EnrichNet highlighted the possible involvement of the identified protein alterations in apoptosis, proteasome protein degradation, heat shock protein action, and signal transduction. Western blot analysis revealed underexpression of vinculin and advanced fragmentation of fermitin-3 in MDS patients. To the best of our knowledge, this is the first time that proteome changes have been identified in the mononuclear cells of MDS patients. Vinculin and fermitin-3, the proteins involved in cell adhesion and integrin signaling, have been shown to be dysregulated in MDS.

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