scholarly journals Pro-Thrombotic Activity of Blood Platelets in Multiple Sclerosis

Cells ◽  
2019 ◽  
Vol 8 (2) ◽  
pp. 110 ◽  
Author(s):  
Joanna Saluk-Bijak ◽  
Angela Dziedzic ◽  
Michal Bijak
Keyword(s):  
Multiple Sclerosis ◽  
Platelet Activation ◽  
Inflammatory Diseases ◽  
Blood Platelets ◽  
Experimental Studies ◽  
Epidemiological Studies ◽  
Membrane Receptors ◽  
Vascular Integrity ◽  
Oxidative Processes ◽  
Specific Membrane

The available data, including experimental studies, clearly indicate an excessive intravascular activation of circulating platelets in multiple sclerosis (MS) and their hyper-responsiveness to a variety of physiological activators. Platelet activation is manifested as an increased adhesion and aggregation and is accompanied by the formation of pro-thrombotic microparticles. Activated blood platelets also show an expression of specific membrane receptors, synthesis many of biomediators, and generation of reactive oxygen species. Epidemiological studies confirm the high risk of stroke or myocardial infarction in MS that are ischemic incidents, strictly associated with incorrect platelet functions and their over pro-thrombotic activity. Chronic inflammation and high activity of pro-oxidative processes in the course of MS are the main factors identified as the cause of excessive platelet activation. The primary biological function of platelets is to support vascular integrity, but the importance of platelets in inflammatory diseases is also well documented. The pro-thrombotic activity of platelets and their inflammatory properties play a part in the pathophysiology of MS. The analysis of platelet function capability in MS could provide useful information for studying the pathogenesis of this disease. Due to the complexity of pathological processes in MS, medication must be multifaceted and blood platelets can probably be identified as new targets for therapy in the future.

scholarly journals Increased Pro-Thrombotic Platelet Activity Associated with Thrombin/PAR1-Dependent Pathway Disorder in Patients with Secondary Progressive Multiple Sclerosis

2020 ◽  
Vol 21 (20) ◽  
pp. 7722
Author(s):  
Angela Dziedzic ◽  
Elzbieta Miller ◽  
Michal Bijak ◽  
Lukasz Przyslo ◽  
Joanna Saluk-Bijak
Keyword(s):  
Multiple Sclerosis ◽  
Mrna Expression ◽  
Platelet Activation ◽  
Blood Platelets ◽  
Surface Expression ◽  
Epidemiological Studies ◽  
Progressive Multiple Sclerosis ◽  
Apolipoprotein A1 ◽  
Platelet Activity ◽  
Activation Markers

Epidemiological studies confirm the high risk of ischemic events in multiple sclerosis (MS) that are associated with increased pro-thrombotic activity of blood platelets. The most potent physiological platelet agonist is thrombin, which activates platelets via cleavage of specific protease-activated receptors (PARs). Our current study is aimed to determine the potential genetics and proteomic abnormalities of PAR1 in both platelets and megakaryocytes, which may have thromboembolic consequences in the course of MS. The obtained results were correlated with the expression level of platelet and megakaryocyte transcripts for APOA1 and A2M genes encoding atherosclerosis biomarkers: apolipoprotein A1 (ApoA1) and α-2-macroglobulin (α2M), respectively. Moreover, PAR1 functionality in MS platelets was assessed by flow cytometry, determining the level of platelet–platelet and platelet–leukocyte aggregates, platelet microparticles and surface expression of P-selectin. As a PAR1 agonist, the synthetic TRAP-6 peptide was used, which made it possible to achieve platelet activation in whole blood without triggering clotting. Comparative analyses showed an elevated level of platelet activation markers in the blood of MS patients compared to controls. The mRNA expression of gene coding α2M was upregulated, whilst ApoA1 was down-regulated, both in platelets and megakaryocytes from MS patients. Furthermore, we observed an increase in both mRNA expression and surface density of PAR1 in platelets and megakaryocytes in MS compared to controls. Both the level of platelet activation markers and PAR1 expression showed a high correlation with the expression of transcripts for APOA1 and A2M genes.

scholarly journals The Impact of SARS-CoV-2 Infection on the Development of Neurodegeneration in Multiple Sclerosis

2021 ◽  
Vol 22 (4) ◽  
pp. 1804 ◽  
Author(s):  
Angela Dziedzic ◽  
Joanna Saluk-Bijak ◽  
Elzbieta Miller ◽  
Marcin Niemcewicz ◽  
Michal Bijak
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrovascular Disease ◽  
Blood Platelets ◽  
Epidemiological Studies ◽  
Essential Elements ◽  
Global Challenge ◽  
Reactive Protein ◽  
Risk Of Death ◽  
Novel Coronavirus ◽  
The Impact

The novel coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), remains a global challenge. Currently, there is some information on the consequences of COVID-19 infection in multiple sclerosis (MS) patients, as it is a newly discovered coronavirus, but its far-reaching effects on participation in neurodegenerative diseases seem to be significant. Recent cases reports showed that SARS-CoV-2 may be responsible for initiating the demyelination process in people who previously had no symptoms associated with any nervous system disorders. It is presently known that infection of SARS-CoV-2 evokes cytokine storm syndrome, which may be one of the factors leading to the acute cerebrovascular disease. One of the substantial problems is the coexistence of cerebrovascular disease and MS in an individual’s life span. Epidemiological studies showed an enhanced risk of death rate from vascular disabilities in MS patients of approximately 30%. It has been demonstrated that patients with severe SARS-CoV-2 infection usually show increased levels of D-dimer, fibrinogen, C-reactive protein (CRP), and overactivation of blood platelets, which are essential elements of prothrombotic events. In this review, the latest knowledge gathered during an ongoing pandemic of SARS-CoV-2 infection on the neurodegeneration processes in MS is discussed.

scholarly journals The microbiome and food that fuels the fire of inflammation

2017 ◽  
Vol 39 (4) ◽  
pp. 16-19
Author(s):  
Silvia Melgar
Keyword(s):  
Metabolic Diseases ◽  
Inflammatory Diseases ◽  
Food Additives ◽  
Experimental Studies ◽  
Treatment Strategies ◽  
Saturated Fat ◽  
Epidemiological Studies ◽  
Host Immune Responses ◽  
High Risk Factors ◽  
Bowel Diseases

Inflammatory bowel diseases (IBD), encompassing two main conditions – Crohn's disease (CD) and ulcerative colitis (UC), are multifactorial chronic intestinal inflammatory diseases with increasing incidence worldwide, especially in countries adopting a westernized lifestyle. Recent findings point towards a major impact of diet on human health since it can affect both the gut microbiota and the host response. Epidemiological studies have identified that the consumption of processed food, red meat, saturated fat and low fibre/vegetables are high-risk factors for IBD, while the consumption of fatty fish, fermentable fibres and vegetables lowers risk for IBD. Experimental studies have supported these findings. Animals fed certain specific diets demonstrate alterations in host immune responses and microbiota composition including the blooming of pathobionts as a result of diet treatment. Recent seminal studies have also provided evidence on the role of food additives such as emulsifiers in IBD and metabolic diseases. In the future, controlled trials and mechanistic studies will identify diet-induced beneficial or triggering mechanisms which will lead to the development of new treatment strategies for these debilitating diseases.

Investigation of the Interaction of Blood Platelets with the Coagulation System at the Site of Plug Formation In Vivo in Man - Effect of Low-Dose Aspirin

1987 ◽  
Vol 57 (01) ◽  
pp. 062-066 ◽  
Author(s):  
P A Kyrle ◽  
J Westwick ◽  
M F Scully ◽  
V V Kakkar ◽  
G P Lewis
Keyword(s):  
Platelet Activation ◽  
Thrombin Generation ◽  
Low Dose ◽  
Bleeding Time ◽  
Blood Platelets ◽  
Dose Aspirin ◽  
Low Dose Aspirin ◽  
Plug Formation ◽  
Granule Release

SummaryIn 7 healthy volunteers, formation of thrombin (represented by fibrinopeptide A (FPA) generation, α-granule release (represented by β-thromboglobulin [βTG] release) and the generation of thromboxane B2 (TxB2) were measured in vivo in blood emerging from a template bleeding time incision. At the site of plug formation, considerable platelet activation and thrombin generation were seen within the first minute, as indicated by a 110-fold, 50-fold and 30-fold increase of FPA, TxB2 and PTG over the corresponding plasma values. After a further increase of the markers in the subsequent 3 minutes, they reached a plateau during the fourth and fifth minute. A low-dose aspirin regimen (0.42 mg.kg-1.day-1 for 7 days) caused >90% inhibition of TxB2formation in both bleeding time blood and clotted blood. At the site of plug formation, a-granule release was substantially reduced within the first three minutes and thrombin generation was similarly inhibited. We conclude that (a) marked platelet activation and considerable thrombin generation occur in the early stages.of haemostasis, (b) α-granule release in vivo is partially dependent upon cyclo-oxygenase-controlled mechanisms and (c) thrombin generation at the site of plug formation is promoted by the activation of platelets.

Potential Role of Inflammation in Associations between Particulate Matter and Heart Failure

2018 ◽  
Vol 24 (3) ◽  
pp. 341-358 ◽  
Author(s):  
Xiaotong Ji ◽  
Yingying Zhang ◽  
Guangke Li ◽  
Nan Sang
Keyword(s):  
Heart Failure ◽  
Particulate Matter ◽  
Inflammatory Response ◽  
Heart Diseases ◽  
Experimental Studies ◽  
Epidemiological Studies ◽  
Inflammatory Mechanism ◽  
High Concentrations ◽  
Future Work ◽  
The Relationship

Recently, numerous studies have found that particulate matter (PM) exposure is correlated with increased hospitalization and mortality from heart failure (HF). In addition to problems with circulation, HF patients often display high expression of cytokines in the failing heart. Thus, as a recurring heart problem, HF is thought to be a disorder characterized in part by the inflammatory response. In this review, we intend to discuss the relationship between PM exposure and HF that is based on inflammatory mechanism and to provide a comprehensive, updated evaluation of the related studies. Epidemiological studies on PM-induced heart diseases are focused on high concentrations of PM, high pollutant load exposure in winter, or susceptible groups with heart diseases, etc. Furthermore, it appears that the relationship between fine or ultrafine PM and HF is stronger than that between HF and coarse PM. However, fewer studies paid attention to PM components. As for experimental studies, it is worth noting that coarse PM may indirectly promote the inflammatory response in the heart through systematic circulation of cytokines produced primarily in the lungs, while ultrafine PM and its components can enter circulation and further induce inflammation directly in the heart. In terms of PM exposure and enhanced inflammation during the pathogenesis of HF, this article reviews the following mechanisms: hemodynamics, oxidative stress, Toll-like receptors (TLRs) and epigenetic regulation. However, many problems are still unsolved, and future work will be needed to clarify the complex biologic mechanisms and to identify the specific components of PM responsible for adverse effects on heart health.

scholarly journals Construction of the ‘minimal’ SRP that interacts with the translating ribosome but not with specific membrane receptors in Escherichia coli

FEBS Letters ◽  
2002 ◽  
Vol 514 (1) ◽  
pp. 70-73 ◽  
Author(s):  
Olga N Avdeeva ◽  
Alexander G Myasnikov ◽  
Petr V Sergiev ◽  
Alexey A Bogdanov ◽  
Richard Brimacombe ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Membrane Receptors ◽  
Specific Membrane

scholarly journals Relationship between Autism Spectrum Disorder and Pesticides: A Systematic Review of Human and Preclinical Models

2021 ◽  
Vol 18 (10) ◽  
pp. 5190
Author(s):  
Judit Biosca-Brull ◽  
Cristian Pérez-Fernández ◽  
Santiago Mora ◽  
Beatriz Carrillo ◽  
Helena Pinos ◽  
...  
Keyword(s):  
Systematic Review ◽  
Autism Spectrum Disorder ◽  
Experimental Studies ◽  
Clinical Signs ◽  
Epidemiological Studies ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Preclinical Studies ◽  
Preclinical Models ◽  
Gestational Exposure

Autism spectrum disorder (ASD) is a complex set of neurodevelopmental pathologies characterized by impoverished social and communicative abilities and stereotyped behaviors. Although its genetic basis is unquestionable, the involvement of environmental factors such as exposure to pesticides has also been proposed. Despite the systematic analyses of this relationship in humans, there are no specific reviews including both human and preclinical models. The present systematic review summarizes, analyzes, and discusses recent advances in preclinical and epidemiological studies. We included 45 human and 16 preclinical studies. These studies focused on Organophosphates (OP), Organochlorine (OC), Pyrethroid (PT), Neonicotinoid (NN), Carbamate (CM), and mixed exposures. Preclinical studies, where the OP Chlorpyrifos (CPF) compound is the one most studied, pointed to an association between gestational exposure and increased ASD-like behaviors, although the data are inconclusive with regard to other ages or pesticides. Studies in humans focused on prenatal exposure to OP and OC agents, and report cognitive and behavioral alterations related to ASD symptomatology. The results of both suggest that gestational exposure to certain OP agents could be linked to the clinical signs of ASD. Future experimental studies should focus on extending the analysis of ASD-like behaviors in preclinical models and include exposure patterns similar to those observed in human studies.

scholarly journals Collagen-induced platelet activation mainly involves the protein kinase C pathway

1990 ◽  
Vol 268 (2) ◽  
pp. 325-331 ◽  
Author(s):  
A Karniguian ◽  
F Grelac ◽  
S Levy-Toledano ◽  
Y J Legrand ◽  
F Rendu
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Phospholipase C ◽  
Platelet Activation ◽  
Membrane Receptors ◽  
Lag Phase ◽  
Response Curves ◽  
Kinase C ◽  
Metabolic Event ◽  
Granule Secretion

This study analyses early biochemical events in collagen-induced platelet activation. An early metabolic event occurring during the lag phase was the activation of PtdIns(4,5)P2-specific phospholipase C. Phosphatidic acid (PtdOH) formation, phosphorylation of P43 and P20, thromboxane B2 (TXB2) synthesis and platelet secretion began after the lag phase, and were similarly time-dependent, except for TXB2 synthesis, which was delayed. Collagen induced extensive P43 phosphorylation, whereas P20 phosphorylation was weak and always lower than with thrombin. The dose-response curves of P43 phosphorylation and granule secretion were similar, and both reached a peak at 7.5 micrograms of collagen/ml, a dose which induced half-maximal PtdOH and TXB2 formation. Sphingosine, assumed to inhibit protein kinase C, inhibited P43 phosphorylation and secretion in parallel. However, sphingosine was not specific for protein kinase C, since a 15 microM concentration, which did not inhibit P43 phosphorylation, blocked TXB2 synthesis by 50%. Sphingosine did not affect PtdOH formation at all, even at 100 microM, suggesting that collagen itself induced this PtdOH formation, independently of TXB2 generation. The absence of external Ca2+ allowed the cleavage of polyphosphoinositides and the accumulation of InsP3 to occur, but impaired P43 phosphorylation, PtdOH and TXB2 formation, and secretion; these were only restored by adding 0.11 microM-Ca2+. In conclusion, stimulation of platelet membrane receptors for collagen initiates a PtdInsP2-specific phospholipase C activation, which is independent of external Ca2+, and might be the immediate receptor-linked response. A Ca2+ influx is indispensable to the triggering of subsequent platelet responses. This stimulation predominantly involves the protein kinase C pathway associated with secretion, and appears not to be mediated by TXB2, at least during its initial stage.

Hypoxic mechanisms in primary headaches

Cephalalgia ◽  
2016 ◽  
Vol 37 (4) ◽  
pp. 372-384 ◽  
Author(s):  
Josefine Britze ◽  
Nanna Arngrim ◽  
Henrik Winther Schytz ◽  
Messoud Ashina
Keyword(s):  
Cluster Headache ◽  
High Altitude ◽  
Acute Mountain Sickness ◽  
Experimental Studies ◽  
Epidemiological Studies ◽  
Primary Headaches ◽  
Secondary Headaches ◽  
Novel Approach ◽  
Calcitonin Gene ◽  
Level Of Knowledge

Background Hypoxia causes secondary headaches such as high-altitude headache (HAH) and headache due to acute mountain sickness. These secondary headaches mimic primary headaches such as migraine, which suggests a common link. We review and discuss the possible role of hypoxia in migraine and cluster headache. Methods This narrative review investigates the current level of knowledge on the relation of hypoxia in migraine and cluster headache based on epidemiological and experimental studies. Findings Epidemiological studies suggest that living in high-altitude areas increases the risk of migraine and especially migraine with aura. Human provocation models show that hypoxia provokes migraine with and without aura, whereas cluster headache has not been reliably induced by hypoxia. Possible pathophysiological mechanisms include hypoxia-induced release of nitric oxide and calcitonin gene-related peptide, cortical spreading depression and leakage of the blood-brain barrier. Conclusion There is a possible link between hypoxia and migraine and maybe cluster headache, but the exact mechanism is currently unknown. Provocation models of hypoxia have yielded interesting results suggesting a novel approach to study in depth the mechanism underlying hypoxia and primary headaches.

Therapeutic Effects of Physical Exercise and the Mesenchymal Stem Cell Secretome by Modulating Neuroinflammatory Response in Multiple Sclerosis

2021 ◽  
Vol 16 ◽  
Author(s):  
Lina María González ◽  
Laura Natalia Ospina ◽  
Laura Elena Sperling ◽  
Orlando Chaparro ◽  
Jaison Daniel Cucarián
Keyword(s):  
Multiple Sclerosis ◽  
Stem Cells ◽  
Physical Exercise ◽  
Disease Progression ◽  
Neuronal Damage ◽  
Experimental Studies ◽  
Chronic Inflammatory Disease ◽  
Therapeutic Effects ◽  
Local Inflammatory Response ◽  
Neuroinflammatory Response

Multiple sclerosis (MS) is a neurodegenerative, demyelinating, and chronic inflammatory disease characterized by central nervous system (CNS) lesions that lead to high levels of disability and severe physical and cognitive disturbances. Conventional therapies are not enough to control the neuroinflammatory process in MS and are not able to inhibit ongoing damage to the CNS. Thus, the secretome of mesenchymal stem cells (MSC-S) has been postulated as a potential therapy that could mitigate symptoms and disease progression. We considered that its combination with physical exercise (EX) could induce superior effects and increase the MSC-S effectiveness in this condition. Recent studies have revealed that both EX and MSC-S share similar mechanisms of action that mitigate auto-reactive T cell infiltration, regulate the local inflammatory response, modulate the proinflammatory profile of glial cells, and reduce neuronal damage. Clinical and experimental studies have reported that these treatments in an isolated way also improve myelination, regeneration, promote the release of neurotrophic factors, and increase the recruitment of endogenous stem cells. Together, these effects reduce disease progression and improve patient functionality. Despite these results, the combination of these methods has not yet been studied in MS. In this review, we focus on molecular elements and cellular responses induced by these treatments in a separate way, showing their beneficial effects in the control of symptoms and disease progression in MS, as well as indicating their contribution in clinical fields. In addition, we propose the combined use of EX and MSC-S as a strategy to boost their reparative and immunomodulatory effects in this condition, combining their benefits on synaptogenesis, neurogenesis, remyelination, and neuroinflammatory response. The findings here reported are based on the scientific evidence and our professional experience that will bring significant progress to regenerative medicine to deal with this condition.

Sign in / Sign up

Export Citation Format

Share Document