scholarly journals The Cytoskeletal Elements MAP2 and NF-L Show Substantial Alterations in Different Stroke Models While Elevated Serum Levels Highlight Especially MAP2 as a Sensitive Biomarker in Stroke Patients

2021 ◽  
Author(s):  
Bianca Mages ◽  
Thomas Fuhs ◽  
Susanne Aleithe ◽  
Alexandra Blietz ◽  
Constance Hobusch ◽  
...  
Keyword(s):  
Animal Models ◽  
Neuronal Damage ◽  
Degradation Products ◽  
Focal Cerebral Ischemia ◽  
Elevated Serum ◽  
Serum Levels ◽  
Ultrastructural Level ◽  
Stroke Patients ◽  
Protein Levels ◽  
Cytoskeletal Elements

AbstractIn the setting of ischemic stroke, the neurofilament subunit NF-L and the microtubule-associated protein MAP2 have proven to be exceptionally ischemia-sensitive elements of the neuronal cytoskeleton. Since alterations of the cytoskeleton have been linked to the transition from reversible to irreversible tissue damage, the present study investigates underlying time- and region-specific alterations of NF-L and MAP2 in different animal models of focal cerebral ischemia. Although NF-L is increasingly established as a clinical stroke biomarker, MAP2 serum measurements after stroke are still lacking. Therefore, the present study further compares serum levels of MAP2 with NF-L in stroke patients. In the applied animal models, MAP2-related immunofluorescence intensities were decreased in ischemic areas, whereas the abundance of NF-L degradation products accounted for an increase of NF-L-related immunofluorescence intensity. Accordingly, Western blot analyses of ischemic areas revealed decreased protein levels of both MAP2 and NF-L. The cytoskeletal alterations are further reflected at an ultrastructural level as indicated by a significant reduction of detectable neurofilaments in cortical axons of ischemia-affected areas. Moreover, atomic force microscopy measurements confirmed altered mechanical properties as indicated by a decreased elastic strength in ischemia-affected tissue. In addition to the results from the animal models, stroke patients exhibited significantly elevated serum levels of MAP2, which increased with infarct size, whereas serum levels of NF-L did not differ significantly. Thus, MAP2 appears to be a more sensitive stroke biomarker than NF-L, especially for early neuronal damage. This perspective is strengthened by the results from the animal models, showing MAP2-related alterations at earlier time points compared to NF-L. The profound ischemia-induced alterations further qualify both cytoskeletal elements as promising targets for neuroprotective therapies.

scholarly journals Adipokine Chemerin Stimulates Progression of Atherosclerosis in ApoE−/− Mice

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Huadong Liu ◽  
Wei Xiong ◽  
Yu Luo ◽  
Hua Chen ◽  
Yaqiong He ◽  
...  
Keyword(s):  
P38 Mapk ◽  
High Fat Diet ◽  
Transforming Growth Factor ◽  
Elevated Serum ◽  
Serum Levels ◽  
Nuclear Antigen ◽  
High Fat ◽  
Aortic Plaque ◽  
Protein Levels ◽  
Progression Of Atherosclerosis

Background. Vascular remodeling is the most critical pathogenesis of atherosclerosis. Adipokine chemerin was known for its relationship with obesity as well as metabolism. Most recently, chemerin was found to play a crucial role in the pathologic process of cardiovascular diseases including coronary heart disease. In this study, we surveyed the role of chemerin in progression of atherosclerosis in ApoE−/− mice. Objective. To investigate the relationship between chemerin and progression of atherosclerosis in ApoE−/− mice and its mechanism. Methods. 8-week-old ApoE−/− mice were fed with high-fat diet to induce the atherosclerosis model. Adenoviruses were transfected for knockdown or overexpression of chemerin gene into aorta. Serums and aortic tissues of ApoE−/− mice were obtained after feeding high-fat diet for 16 weeks. HE staining and oil red staining were performed to evaluate aortic plaque. ELISA was performed to explore serum levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and transforming growth factor-β1 (TGF-β1). Real-time PCR and western blotting were carried out to investigate the mRNA and protein levels of chemerin, nuclear factor-κB p65 (NF-κBp65), proliferating cell nuclear antigen (PCNA), phosphorylated p38 mitogen-activated protein kinase (p-p38-MAPK), phosphorylated c-Jun N-terminal kinase (p-JNK), and phosphorylated extracellular signal regulated kinase 1/2 (p-ERK 1/2). Result. Aortic plaque formation was significantly induced by high-fat diet in ApoE−/− mice. Simultaneously, elevated serum levels of TNF-α and IL-1β and elevated mRNA and protein levels of chemerin, NF-κBp65, PCNA, p-p38-MAPK, p-JNK, and p-ERK 1/2 were found in ApoE−/− mice. After aortic chemerin gene was inhibited by adenovirus, aortic atherosclerosis induced by high-fat diet was significantly meliorated, serum levels of TNF-α and IL-1β decreased, mRNA and protein levels of NF-κBp65, PCNA, p-p38-MAPK, p-JNK, and p-ERK 1/2 decreased simultaneously. Conclusion. Our study revealed that chemerin stimulated the progression of atherosclerosis in ApoE−/− mice.

scholarly journals Thrombin antithrombin complex and IL-18 serum levels in stroke patients

2010 ◽  
Vol 2 (1) ◽  
pp. 1 ◽  
Author(s):  
Ornella Piazza ◽  
Giuliana Scarpati ◽  
Simona Cotena ◽  
Maria Lonardo ◽  
Rosalba Tufano
Keyword(s):  
Antithrombin Iii ◽  
Degradation Products ◽  
Focal Cerebral Ischemia ◽  
Serum Levels ◽  
High Serum ◽  
Fibrin Degradation Products ◽  
Markers Of Inflammation ◽  
Complex Picture ◽  
Thrombin Antithrombin Iii Complex ◽  
D Dimer

The complex picture of inflammation and coagulation alterations comes to life in acute stroke phases. Increasing evidence points to a strong interaction and extensive crosstalk between the inflammation and coagulation systems: the interest towards this relationship has increased since recent experimental research showed that the early administration of antithrombin III (ATIII) decreases the volume of ischemia in mice and might be neuroprotective, playing an antiinflammatory role. We aimed to establish the extent of the relationship among markers of inflammation (S100B and IL-18) and procoagulant and fibrinolytic markers (ATIII, thrombin-antithrombin III complex (TAT), Fibrin Degradation Products (FDP), D-dimer) in 13 comatose patients affected by focal cerebral ischemia. Plasma levels of TAT, D-dimer and FDP, IL18 and S100B were increased. IL-18 and S100B high serum levels in ischemic patients suggest an early activation of the inflammatory cascade in acute ischemic injury. The basic principles of the interaction between inflammatory and coagulation systems are revised, from the perspective that simultaneous modulation of both coagulation and inflammation, rather than specific therapies aimed at one of these systems could be more successful in stroke therapy.

Effects of long-term elevated serum levels of growth hormone on life expectancy of mice: Lessons from transgenic animal models

1993 ◽  
Vol 68 (1-3) ◽  
pp. 71-87 ◽  
Author(s):  
Eckhard Wolf ◽  
Eva Kahnt ◽  
Jörn Ehrlein ◽  
Walter Hermanns ◽  
Gottfried Brem ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Animal Models ◽  
Life Expectancy ◽  
Elevated Serum ◽  
Serum Levels ◽  
Transgenic Animal ◽  
Transgenic Animal Models

scholarly journals Intravascular Coagulation in Acute Leukemia: Clinical and Subclinical Abnormalities

Blood ◽  
1972 ◽  
Vol 40 (5) ◽  
pp. 709-718 ◽  
Author(s):  
Harvey R. Gralnick ◽  
Sally Marchesi ◽  
Harry Givelber
Keyword(s):  
Acute Leukemia ◽  
Degradation Products ◽  
Elevated Serum ◽  
Poor Response ◽  
Serum Levels ◽  
Heparin Therapy ◽  
Plasma Fibrinogen ◽  
Factor V ◽  
Intravascular Coagulation ◽  
Laboratory Evidence

Abstract Fifteen patients with acute leukemia were found to have evidence of a generalized hemostatic disorder. These patients could be divided into three groups. The first group consisted of three patients with increased fibrinogen catabolism without clinical or laboratory evidence of intravascular coagulation. The second group of five patients had laboratory evidence of intravascular coagulation without clinically evident bleeding or thrombosis. The third group of seven patients developed symptomatic intravascular coagulation characterized by bleeding, renal failure, and poor response to platelet transfusions. Laboratory evidence for intravascular coagulation in these patients included falling plasma fibrinogen and factor V levels and elevated serum levels of fibrinogen degradation products. Heparin therapy resulted in clinical improvement in all seven patients. Rising plasma fibrinogen and factor V levels correlated with a beneficial clinical response to heparin. Increased fibrinogen catabolism, asymptomatic intravascular coagulation, and symptomatic intravascular coagulation form part of a spectrum of generalized hemostatic disorders in acute leukemia.

scholarly journals Ornithine Decarboxylase Knockdown Exacerbates Transient Focal Cerebral Ischemia-Induced Neuronal Damage in Rat Brain

2001 ◽  
Vol 21 (8) ◽  
pp. 945-954 ◽  
Author(s):  
Raghavendra Vemuganti L. Rao ◽  
Aclan Dogan ◽  
Kellie K. Bowen ◽  
Robert J. Dempsey
Keyword(s):  
Cerebral Ischemia ◽  
Ornithine Decarboxylase ◽  
Neuronal Damage ◽  
Focal Cerebral Ischemia ◽  
Infarct Volume ◽  
Artery Occlusion ◽  
Motor Deficits ◽  
Spontaneously Hypertensive ◽  
Protein Levels ◽  
Transient Focal Cerebral Ischemia

Transient cerebral ischemia leads to increased expression of ornithine decarboxylase (ODC). Contradicting studies attributed neuroprotective and neurotoxic roles to ODC after ischemia. Using antisense oligonucleotides (ODNs), the current study evaluated the functional role of ODC in the process of neuronal damage after transient focal cerebral ischemia induced by middle cerebral artery occlusion (MCAO) in spontaneously hypertensive rats. Transient MCAO significantly increased the ODC immunoreactive protein levels and catalytic activity in the ipsilateral cortex, which were completely prevented by the infusion of antisense ODN specific for ODC. Transient MCAO in rats infused with ODC antisense ODN increased the infarct volume, motor deficits, and mortality compared with the sense or random ODN-infused controls. Results of the current study support a neuroprotective or recovery role, or both, for ODC after transient focal ischemia.

Association of Serum Malondialdehyde and C-reactive protein Levels with Exacerbations of Chronic Obstructive Pulmonary Disease

2022 ◽  
Vol 18 ◽  
Author(s):  
Amir Behnam Kharazmi ◽  
Atefeh Abedini ◽  
Arda Kiani ◽  
Shahriar Barouti ◽  
Shooka Mohammadi
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Pulmonary Disease ◽  
Elevated Serum ◽  
Serum Levels ◽  
Prognostic Indicators ◽  
Chronic Obstructive ◽  
C Reactive Protein ◽  
Obstructive Pulmonary Disease ◽  
Protein Levels ◽  
Reactive Protein

Background: Chronic obstructive pulmonary disease (COPD) is related to oxidant/antioxidant imbalance and systemic inflammation Objective: This study was conducted to evaluate associations of serum levels of C-reactive protein (CRP) and malondialdehyde (MDA) with the severity and exacerbations of COPD. Methods: A matched case-control study was performed among 200 COPD patients (100 cases and 100 controls) who were referred to Masih Daneshvari Hospital in Tehran, Iran. Cases were exacerbators with equal to or greater than two ambulatory exacerbations or one hospitalization; controls were non-exacerbators who had one/no ambulatory exacerbation during the preceding 12 months. Blood samples were collected for CRP, MDA, and erythrocyte sedimentation rate (ESR) analysis. In addition, spirometry, the COPD assessment test (CAT) score, the modified Medical Research Council (mMRC) dyspnea scale, and the BODEx index were applied. Results: The mean (SD) age of the patients was 65.31 (8.46) years. Those with exacerbations had significantly lower FEV1 and higher CRP, MDA, ESR, BMI, BODEx index, CAT, and mMRC scores compared to non-exacerbators. There were significant differences in CRP, MDA, ESR, FVC, FEV1, FEV1/FVC, BMI, BODEx index, mMRC, and CAT scores between the GOLD group. Moreover, multivariate analysis showed that higher levels of CRP (OR=0.61, p=0.023), MDA (OR=0.28, p=0.001), ESR (OR=0.86, p=0.029), CAT score (OR=0.84, p=0.012), BODEx index (OR=0.89, p <0.001), BMI (OR=0.42, p <0.001), and lower FEV1% (OR=0.77, p <0.001) were independent risk factors for frequent exacerbations. Conclusion: In conclusion, elevated serum MDA and CRP levels in combination may serve as prognostic indicators of the severity and exacerbation of COPD.

scholarly journals Correlation between CH2DS2-VASc Score and Serum Leptin Levels in Cardioembolic Stroke Patients: The Impact of Metabolic Syndrome

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Anna Szczepańska-Szerej ◽  
Jacek Kurzepa ◽  
Aneta Grabarska ◽  
Joanna Bielewicz ◽  
Ewa Wlizło-Dyś ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Elevated Serum ◽  
Female Gender ◽  
Serum Levels ◽  
Cardioembolic Stroke ◽  
Control Group ◽  
Stroke Patients ◽  
Serum Leptin ◽  
Potential Biomarker ◽  
The Impact

Objective. To determine adipokines levels in patients with different etiologic subtypes of acute ischemic stroke (AIS) and metabolic syndrome (MetS) status.Methods. Serum adiponectin, leptin, and resistin levels were determined by ELISA in 99 AIS patients and 59 stroke-free control group subjects. Stroke patients were grouped based on MetS, modified TOAST classification, and CHA2DS2-VASc scale in case of cardioembolic stroke following atrial fibrillation.Results. No differences were found in all adipokine serum levels between AIS patients and appropriately matched control group. MetS-AIS patients had significantly higher leptin levels (22.71 ± 19.01 ng/ml versus 8.95 ± 9.22 ng/ml,p<0.001) and lower adiponectin levels (10.71 ± 8.59 ng/ml versus 14.93 ± 10.95 ng/ml,p<0.05) than non-MetS-AIS patients. In patients with cardioembolic stroke, leptin levels were significantly higher than in remaining stroke cases (19.57 ± 20.53 ng/ml versus 13.17 ± 12.36 ng/ml,p<0.05) and CHA2DS2-VASc score positively correlated with leptin levels only (p<0.001). Analysis of individual components of CHA2DS2-VASc score showed that hypertension, female gender, and diabetes had greatest impact on elevated serum leptin level.Conclusion. This pilot study revealed that leptin could be a potential biomarker for risk stratification of cardioembolic stroke in MetS patients and that heterogeneity of stroke subtypes should be considered for more refined and precise clinical stroke studies.

Negative Correlation Between Serum Levels of Homocysteine and Apolipoprotein M

2019 ◽  
Vol 19 (2) ◽  
pp. 120-126
Author(s):  
J. Wei ◽  
Y. Yu ◽  
Y. Feng ◽  
J. Zhang ◽  
Q. Jiang ◽  
...  
Keyword(s):  
Negative Correlation ◽  
Hepg2 Cells ◽  
Serum Levels ◽  
Significant Negative Correlation ◽  
Mrna Levels ◽  
Rt Pcr ◽  
Apolipoprotein M ◽  
Protein Mass ◽  
Protein Levels ◽  
Phosphoinositide 3 Kinase

Background: Homocysteine (Hcy) has been suggested as an independent risk factor for atherosclerosis. Apolipoprotein M (apoM) is a constituent of the HDL particles. The goal of this study was to examine the serum levels of homocysteine and apoM and to determine whether homocysteine influences apoM synthesis. Methods: Serum levels of apoM and Hcy in 17 hyperhomocysteinemia (HHcy) patients and 19 controls were measured and their correlations were analyzed. Different concentrations of homocysteine (Hcy) and LY294002, a specific phosphoinositide 3- kinase (PI3K) inhibitor, were used to treat HepG2 cells. The mRNA levels were determined by RT-PCR and the apoM protein mass was measured by western blot. Results: We found that decreased serum apoM levels corresponded with serum HDL levels in HHcy patients, while the serum apoM levels showed a statistically significant negative correlation with the serum Hcy levels. Moreover, apoM mRNA and protein levels were significantly decreased after the administration of Hcy in HepG2 cells, and this effect could be abolished by addition of LY294002. Conclusions: resent study demonstrates that Hcy downregulates the expression of apoM by mechanisms involving the PI3K signal pathway.

Brain-derived neurotrophic factor is associated with coronary macrophage infiltrates in patients with acute coronary syndrome

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
R.A Montone ◽  
M Camilli ◽  
M Russo ◽  
M Del Buono ◽  
F Gurguglione ◽  
...  
Keyword(s):  
Acute Coronary Syndrome ◽  
Neurotrophic Factor ◽  
Serum Levels ◽  
Brain Derived Neurotrophic Factor ◽  
C Reactive Protein ◽  
St Segment Elevation ◽  
Protein Levels ◽  
Reactive Protein ◽  
Coronary Syndrome ◽  
St Segment

Abstract Background Brain-derived neurotrophic factor (BDNF) is a neurotrophine that plays a key role in the regulation of both central and peripheral nervous system. Moreover, BDNF is secreted in multiple tissues and exerts systemic, autocrine, and paracrine effects in the cardiovascular system. Of importance, BDNF expression was enhanced in macrophages and smooth muscle cells in atherosclerotic coronary arteries and may be involved in thrombus formation. Thus, BDNF has been suggested as an important link between inflammation and thrombosis, potentially involved in the pathogenesis of acute coronary syndrome (ACS). Purpose In our study we aimed at assessing serum levels of BDNF in patients with ACS, evaluating differences according to clinical presentation [ST-segment elevation myocardial infarction (STEMI) vs. Non-ST-segment elevation ACS (NSTE-ACS)]. Moreover, we assessed the presence of optical coherence (OCT)-defined macrophage infiltrates (MØI) in the culprit vessel of ACS patients and evaluated their relationship with BDNF levels. Methods ACS patients were prospectively selected. Blood samples were collected at admission and serum levels of BDNF were subsequently assessed. Presence of OCT-defined MØI along the culprit vessel was assessed. Results 166 ACS patients were enrolled [mean age 65.3±11.9 years, 125 (75.3%) male, 109 STEMI, 57 NSTE-ACS]. Serum levels of BDNF were higher among STEMI patients compared with NSTE-ACS [median (IQR) 2.48 pg/mL (1.54–3.34) vs. 2.12 pg/mL (1.34–2.47), p=0.007], while C-reactive protein levels did not differ between the two groups. OCT assessment was performed in 53 patients and MØI were detected in 27 patients. Of importance, patients with MØI in the culprit vessel had higher levels of BDNF compared with patients without MØI [median (IQR) 2.23 pg/mL (1.38–2.53) vs. 1.41 pg/mL (0.93–2.07), p=0.023], while C-reactive protein levels did not differ between the two groups. Of note, at multivariate regression analysis BDNF levels were independent predictor of MØI [OR: 2.20; 95% CI (1.02–4.74), p=0.043]. Conclusions Serum levels of BDNF may reliable identify the presence of local macrophage inflammatory infiltrates in patients with ACS. Moreover, BDNF levels are higher in patients with STEMI compared with NSTE-ACS. Taken together, these data suggest that BDNF may represent an interesting link between local inflammatory activation and enhanced thrombosis in ACS. BDNF serum levels Funding Acknowledgement Type of funding source: None

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