Targeting Vascular Impairment, Neuroinflammation, and Oxidative Stress Dynamics with Whole-Body Cryotherapy in Multiple Sclerosis Treatment.

Multiple sclerosis (MS), traditionally perceived as a neurodegenerative disease, exhibits significant vascular alternations, including blood-brain barrier (BBB) disruption, which may predispose patients to increased cardiovascular risks. This vascular dysfunction is intricately linked with the infiltration of immune cells into the central nervous system (CNS), which plays a significant role in perpetuating neuroinflammation. Additionally, oxidative stress serves not only as a byproduct of inflammatory processes but also as an active contributor to neural damage. The synthesis of these multifaceted aspects highlights the importance of understanding their cumulative impact on MS progression. This review reveals that the triad of vascular damage, chronic inflammation, and oxidative imbalance may be considered interdependent processes that exacerbate each other, underscoring the need for holistic and multi-targeted therapeutic approaches in MS management. There is a necessity for reevaluating MS treatment strategies to encompass these overlapping pathologies, offering insights for future research and potential therapeutic interventions. Whole-body cryotherapy (WBCT) emerges as one of the potential avenues for holistic MS management approaches which may alleviate the triad of MS progression factors in multiple ways.

The Power of Psychobiotics in Depression: A Modern Approach through the Microbiota-Gut-Brain Axis: A Literature Review.

The microbiota-gut-brain (MGB) axis is a complex communication network linking the gut, microbiota, and brain, influencing various aspects of health and disease. Dysbiosis, a disturbance in the gut microbiome equilibrium, can significantly impact the MGB axis, leading to alterations in microbial composition and function. Emerging evidence highlights the connection between microbiota alterations and neurological and psychiatric disorders, including depression. This review explores the potential of psychobiotics in managing depressive disorders, emphasizing their role in restoring microbial balance and influencing the MGB axis. Psychobiotics exhibit positive effects on the intestinal barrier, immune response, cortisol levels, and the hypothalamic-pituitary-adrenal (HPA) axis. Studies suggest that probiotics may serve as an adjunct therapy for depression, especially in treatment-resistant cases. This review discusses key findings from studies on psychobiotics interventions, emphasizing their impact on the gut-brain axis and mental health. The increasing acceptance of the expanded concept of the MGB axis underscores the importance of microorganisms in mental well-being. As our understanding of the microbiome's role in health and disease grows, probiotics emerge as promising agents for addressing mental health issues, providing new avenues for therapeutic interventions in depressive disorders.

The Progress in Molecular Transport and Therapeutic Development in Human Blood-Brain Barrier Models in Neurological Disorders.

The blood-brain barrier (BBB) is responsible for maintaining homeostasis within the central nervous system (CNS). Depending on its permeability, certain substances can penetrate the brain, while others are restricted in their passage. Therefore, the knowledge about BBB structure and function is essential for understanding physiological and pathological brain processes. Consequently, the functional models can serve as a key to help reveal this unknown. There are many in vitro models available to study molecular mechanisms that occur in the barrier. Brain endothelial cells grown in culture are commonly used to modeling the BBB. Current BBB platforms include: monolayer platforms, transwell, matrigel, spheroidal, and tissue-on-chip models. In this paper, the BBB structure, molecular characteristic, as well as its dysfunctions as a consequence of aging, neurodegeneration, or under hypoxia and neurotoxic conditions are presented. Furthermore, the current modelling strategies that can be used to study BBB for the purpose of further drugs development that may reach CNS are also described.

Quantitative and structural changes of blood platelet cytoskeleton proteins in multiple sclerosis (MS).

Epidemiological studies show that cardiovascular events related to platelet hyperactivity remain the leading causes of death among multiple sclerosis (MS) patients. Quantitative or structural changes of platelet cytoskeleton alter their morphology and function. Here, we demonstrated, for the first time, the structural changes in MS platelets that may be related to their hyperactivity. MS platelets were found to form large aggregates compared to control platelets. In contrast to the control, the images of overactivated, irregularly shaped MS platelets show changes in the cytoskeleton architecture, fragmented microtubule rings. Furthermore, MS platelets have long and numerous pseudopodia rich in actin filaments. We showed that MS platelets and megakaryocytes, overexpress ß1-tubulin and ß-actin mRNAs and proteins and have altered post-translational modification patterns. Moreover, we identified two previously undisclosed mutations in the gene encoding ß1-tubulin in MS. We propose that the demonstrated structural changes of platelet cytoskeleton enhance their ability to adhere, aggregate, and degranulate fueling the risk of adverse cardiovascular events in MS.

Effect of SARS-CoV-2 Infection and BNT162b2 Vaccination on the mRNA Expression of Genes Associated with Angiogenesis.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), discovered in December 2019 in Wuhan, China, caused the coronavirus disease 2019 (COVID-19). Due to the rate of spread of this virus, the World Health Organization, in March 2020, recognised COVID-19 as a worldwide pandemic. The disease is multisystemic with varying degrees of severity. Unfortunately, despite intensive research, the molecular changes caused by SARS-CoV-2 remain unclear. Mechanisms affected by the virus infection include endothelial dysfunction and angiogenesis. Similarly, the vaccines developed so far affect the process of angiogenesis, contributing to the development of undesirable effects on part of the cardiovascular system. The presented research aimed to investigate the impact of the SARS-CoV-2 infection and the Pfizer Comirnaty vaccine (BNT162b2) on the molecular aspect of angiogenesis. We found that convalescents vaccinated with one dose of BNT162b2 were characterised by higher MMP-7 (metalloproteinases 7) expression than non-vaccinated convalescents and healthy volunteers vaccinated with one dose of BNT162b2. Moreover, non-vaccinated convalescents showed increased mRNA expression of ADAMTS1 (ADAM metallopeptidase with thrombospondin type 1 motif 1) compared to healthy volunteers vaccinated with one dose of BNT162b2. In addition, we showed significant sex differences in the expression of MMP-7. In conclusion, the results of our study suggest a significant impact of SARS-CoV-2 infection and vaccination on the course of angiogenesis at the molecular level.

Neurodegeneration and its potential markers in the diagnosing of secondary progressive multiple sclerosis. A review.

Approximately 70% of relapsing-remitting multiple sclerosis (RRMS) patients will develop secondary progressive multiple sclerosis (SPMS) within 10-15 years. This progression is characterized by a gradual decline in neurological functionality and increasing limitations of daily activities. Growing evidence suggests that both inflammation and neurodegeneration are associated with various pathological processes throughout the development of MS; therefore, to delay disease progression, it is critical to initiate disease-modifying therapy as soon as it is diagnosed. Currently, a diagnosis of SPMS requires a retrospective assessment of physical disability exacerbation, usually over the previous 6-12 months, which results in a delay of up to 3 years. Hence, there is a need to identify reliable and objective biomarkers for predicting and defining SPMS conversion. This review presents current knowledge of such biomarkers in the context of neurodegeneration associated with MS, and SPMS conversion.

Polymorphic variations and mRNA expression of the genes encoding interleukins as well as enzymes of oxidative and nitrative stresses as a potential risk of nephrolithiasis development.

Urolithiasis is one of the most common urological diseases worldwide with an unclear aetiology. However, a growing body of evidence suggests the potential role of molecular disturbances of the inflammation as well as oxidative and nitrative stresses, in the pathogenesis of urolithiasis. Therefore, we aimed to detect the potential association between six selected single-nucleotide polymorphisms (SNPs) and the development of nephrolithiasis. Moreover, we verified the association of urolithiasis development and mRNA expression of IL-6, IL-8, SOD2, and NOS2 in peripheral blood mononuclear cells (PBMCs). Total genomic DNA and mRNA were isolated from the peripheral blood of 112 patients with urolithiasis and 114 healthy subjects. Using Taq-Man® probes, we genotyped the following SNPs: rs1800797 and rs2069845 in IL-6, rs2227307 in IL-8, rs4880 in SOD2, rs2297518 and rs2779249 in NOS2. In turn, the evaluation of mRNA expression was performed using real-time PCR and 2-ΔCt methods. We found that the C/T genotype of the c.47 T>C-SOD2 SNP increased the frequency of urolithiasis occurrence whereas the T/T homozygote of the same polymorphism decreased the risk of urolithiasis development in the Polish population. Moreover, our study confirmed that patients with urolithiasis were characterised by decreased IL-6, IL-8, and SOD2 mRNA expression levels compared to the controls. In conclusion, our results suggest that polymorphic variants and changes in mRNA expression of IL-6, IL8, SOD2, and NOS2 may be involved in the pathophysiology of urolithiasis.

The role of SOD2 and NOS2 genes in the molecular aspect of bladder cancer pathophysiology.

Bladder cancer (BC) is a severe health problem of the genitourinary system and is characterised by a high risk of recurrence. According to the recent GLOBOCAN report, bladder cancer accounts for 3% of diagnosed cancers in the world, taking 10th place on the list of the most common cancers. Despite numerous studies, the full mechanism of BC development remains unknown. Nevertheless, precious results suggest a crucial role of oxidative stress in the development of BC. Therefore, this study explores whether the c. 47 C > T (rs4880)-SOD2, (c. 1823 C > T (rs2297518) and g.-1026 C > A (rs2779249)-NOS2(iNOS) polymorphisms are associated with BC occurrence and whether the bladder carcinogenesis induces changes in SOD2 and NOS2 expression and methylation status in peripheral blood mononuclear cells (PBMCs). In this aim, the TaqMan SNP genotyping assay, TaqMan Gene Expression Assay, and methylation-sensitive high-resolution melting techniques were used to genotype profiling and evaluate the expression of the genes and the methylation status of their promoters, respectively. Our findings confirm that heterozygote of the g.-1026 C > A SNP was associated with a decreased risk of BC. Moreover, we detected that BC development influenced the expression level and methylation status of the promoter region of investigated genes in PBMCs. Concluding, our results confirmed that oxidative stress, especially NOS2 polymorphisms and changes in the expression and methylation of the promoters of SOD2 and NOS2 are involved in the cancer transformation initiation of the cell urinary bladder.

Remyelination in multiple sclerosis from the miRNA perspective.

Remyelination relies on the repair of damaged myelin sheaths, involving microglia cells, oligodendrocyte precursor cells (OPCs), and mature oligodendrocytes. This process drives the pathophysiology of autoimmune chronic disease of the central nervous system (CNS), multiple sclerosis (MS), leading to nerve cell damage and progressive neurodegeneration. Stimulating the reconstruction of damaged myelin sheaths is one of the goals in terms of delaying the progression of MS symptoms and preventing neuronal damage. Short, noncoding RNA molecules, microRNAs (miRNAs), responsible for regulating gene expression, are believed to play a crucial role in the remyelination process. For example, studies showed that miR-223 promotes efficient activation and phagocytosis of myelin debris by microglia, which is necessary for the initiation of remyelination. Meanwhile, miR-124 promotes the return of activated microglia to the quiescent state, while miR-204 and miR-219 promote the differentiation of mature oligodendrocytes. Furthermore, miR-138, miR-145, and miR-338 have been shown to be involved in the synthesis and assembly of myelin proteins. Various delivery systems, including extracellular vesicles, hold promise as an efficient and non-invasive way for providing miRNAs to stimulate remyelination. This article summarizes the biology of remyelination as well as current challenges and strategies for miRNA molecules in potential diagnostic and therapeutic applications.

Circulating Serum VEGF, IGF-1 and MMP-9 and Expression of Their Genes as Potential Prognostic Markers of Recovery in Post-Stroke Rehabilitation-A Prospective Observational Study.

The key period in post-stroke recovery is the first three months due to the high activity of spontaneous and therapeutic-induced processes related to neuroplasticity, angiogenesis and reperfusion. Therefore, the present study examines the expression of VEGF, IGF-1 and MMP-9 proteins and their genes to identify biomarkers that can prognose brain repair ability and thus estimate the outcome of stroke. It also identifies possible associations with clinical scales, including cognitive assessment and depression scales. The study group comprised 32 patients with moderate ischemic stroke severity, three to four weeks after incident. The results obtained after three-week hospitalization indicate a statistically significant change in clinical parameter estimations, as well as in MMP9 and VEGF protein and mRNA expression, over the rehabilitation process. Our findings indicate that combined MMP9 protein and mRNA expression might be a useful biomarker for cognitive improvement in post-stroke patients, demonstrating 87% sensitivity and 71% specificity (p < 0.0001).

Variability, Expression, and Methylation of IL-6 and IL-8 Genes in Bladder Cancer Pathophysiology.

Bladder cancer (BC) is the 10th most common form of cancer globally, but its complete aetiology is still unknown. Nevertheless, there is evidence that chronic inflammation plays a role in the development and progression of BC. Therefore, the presented study aimed to detect a potential association between selected single nucleotide polymorphisms (SNPs)-rs1800797 and rs2069845 in IL-6 and rs2227307 in IL-8-and BC development, as well as to identify the impact of BC on the level of expression and methylation of IL-6 and IL-8 promoters in PBMCs with the use of the TaqMan SNP genotyping assay, TaqMan gene expression assay, and methylation-sensitive high-resolution melting techniques. We did not find any association between the genotypes and combined genotypes of all studied polymorphisms and the occurrence of BC. However, we found that BC patients were characterised by decreased IL-6 and IL-8 mRNA expression levels compared to the controls. Additionally, the methylation status of the IL-6 promoter was higher in controls than in BC patients. Our findings suggest that inflammation may be involved in the development and progression of BC.

Possible role of the NLRP3 inflammasome and the gut-brain axis in multiple sclerosis-related depression.

Multiple sclerosis (MS) is an autoimmune and demyelinating disease of the central nervous system that results from complex interactions between genetic and environmental determinants. Patients with MS exhibit a high risk of depression, however, the exact pathomechanisms remain largely unknown. It is becoming widely accepted that the gut-brain axis (GBA) disorders may exert an influence on neuroinflammation and psychiatric symptoms, including so-called MS-related depression. The element suggested as a bridge between intestinal disorders, depression, and MS is an inflammatory response with the central role of the NLR family pyrin domain containing 3 (NLRP3) inflammasome. The pro-inflammatory activity of effector cytokines of the NLRP3 inflammasome forms the hypothesis that it is actively involved in the development of inflammatory and autoimmune diseases. Despite extensive reviews considering the possible origins of MS-related depression, its complex pathophysiology prevents any easy determination of its underlying mechanisms. This paper aims to discuss molecular mechanisms related to the GBA axis that can mediate dysbiosis, intestinal barrier dysfunction, disruption of blood-brain barrier integrity, neuroinflammation, and subsequent manifestation of MS-related major depressive disorder.

Probiotics and Commensal Gut Microbiota as the Effective Alternative Therapy for Multiple Sclerosis Patients Treatment.

The gut-brain axis (GBA) refers to the multifactorial interactions between the intestine microflora and the nervous, immune, and endocrine systems, connecting brain activity and gut functions. Alterations of the GBA have been revealed in people with multiple sclerosis (MS), suggesting a potential role in disease pathogenesis and making it a promising therapeutic target. Whilst research in this field is still in its infancy, a number of studies revealed that MS patients are more likely to exhibit modified microbiota, altered levels of short-chain fatty acids, and enhanced intestinal permeability. Both clinical and preclinical trials in patients with MS and animal models revealed that the administration of probiotic bacteria might improve cognitive, motor, and mental behaviors by modulation of GBA molecular pathways. According to the newest data, supplementation with probiotics may be associated with slower disability progression, reduced depressive symptoms, and improvements in general health in patients with MS. Herein, we give an overview of how probiotics supplementation may have a beneficial effect on the course of MS and its animal model. Hence, interference with the composition of the MS patient's intestinal microbiota may, in the future, be a grip point for the development of diagnostic tools and personalized microbiota-based adjuvant therapy.

Extremely low frequency electromagnetic field reduces oxidative stress during the rehabilitation of post-acute stroke patients.

BACKGROUND: One of the therapeutic methods used in stroke rehabilitation is magnetotherapy using extremely low frequency and variable pulse shape electromagnetic field (ELF-EMF). OBJECTIVES: The aim of our study was to investigate the effect of magnetotherapy on the condition of postacute stroke patients, as measured by plasma oxidative stress markers and clinical parameters which show the progress of rehabilitation. MATERIAL AND METHODS: The selected 57 post-stroke patients were divided into 2 groups, those with ELFEMF therapy and those without. The level of oxidative stress in the plasma was estimated by typical markers: thiobarbituric acid reactive substances (TBARS), thiol groups, and carbonyl groups. The effect of ELF-EMF on the course of the patients' rehabilitation following ischemic stroke was evaluated with the use of scales of physical activity and mental state: Activities of Daily Living (ADL), Mini-Mental State Examination (MMSE) and Geriatric Depression Scale (GDS). RESULTS: Our comparative analysis showed that all parameters of oxidative stress are significantly reduced during rehabilitation using ELF-EMF, compared to the control group rehabilitated only by kinesiotherapy. We also recorded much higher therapeutic benefits using magnetotherapy, which revealed a significant improvement of clinimetric parameters. CONCLUSIONS: The ELF-EMF therapy meaningfully improves the overall condition of patients through a decrease of oxidative stress markers and it significantly affects the psychophysical abilities of patients after stroke. The change in carbonyl group level correlates with the change in the degree of physical and mental disability; therefore, it could be a marker for the effectiveness of rehabilitation.

Pharmacological and Non-pharmacological Therapies of Cognitive Impairment in Multiple Sclerosis.

BACKGROUND: Cognitive impairment is one of the most important clinical features of neurodegenerative disorders including multiple sclerosis (MS). Conducted research shows that up to 65 percent of MS patients have cognitive deficits such as episodic memory, sustained attention, reduced verbal fluency; however, the cognitive MS domain is information processing speed. It is the first syndrome of cognitive dysfunction and the most widely affected in MS. Occasionally these impairments occur even before the appearance of physical symptoms. METHODS: Therefore, this review focused on the current status of our knowledge about possible methods of treatment cognitive impairment in MS patients including novel strategies. Research and online content was performed using Medline and EMBASE databases. RESULTS: The most recent research suggests that cognitive impairment is correlated with brain lesion volume and brain atrophy. The examination of the cognitive impairment is usually based on particular neuropsychological batteries. However, it can be not enough to make a precise diagnosis. This creates a demand to find markers that might be useful for identifying patients with risk of cognitive impairment at an early stage of the disease. Currently the most promising methods consist of neuroimaging indicators, such as diffusion tensor imaging, the magnetization transfer ratio, and N-acetyl aspartate levels. Diagnosis problems are strictly connected with treatment procedures. There are two main cognitive therapies: pharmacological (disease modifying drugs (DMD), symptomatic treatments) and non-pharmacological interventions that are focused on psychological and physical rehabilitation. Some trials have shown a positive association between physical activity and the cognitive function. CONCLUSION: This article is an overview of the current state of knowledge related to cognition impairment treatment in MS. Additionally, novel strategies for cognitive impairments such as cryostimulation and other complementary methods are presented.

[Inflammatory processes in the pathogenesis of acute coronary syndromes]. / Udzial procesów zapalnych w patogenezie ostrych zespolów wiencowych.

Cardiovascular diseases, including acute coronary syndromes (ACS), are one of the most serious problems of modern medicine and therefore every year 4 million Europeans have died. It is now believed that elevated levels of inflammatory factors in the blood promotes the development cardiovascular events and chronic inflammation plays a key role in the pathogenesis of atherosclerosis. Intensively conducted research in many centers in the world can confirm the desirability of introducing anti-inflammatory therapy to standard drug therapy. The balance between pro- and anti-inflammatory processes affect the risk of developing ACS.

Markers of oxidative/nitrative damage of plasma proteins correlated with EDSS and BDI scores in patients with secondary progressive multiple sclerosis.

OBJECTIVES: The objective of the present study was to evaluate oxidative/nitrative stress in the plasma of 50 patients suffering from the secondary progressive course of multiple sclerosis (MS), and to verify its correlation with physical and mental disability as assessed by the Expanded Disability Status Scale (EDSS), and the Beck Depression Inventory (BDI). METHODS: Oxidative and nitrative damage to proteins was determined by the level of carbonyl groups and 3-nitrotyrosine using ELISA test. Based on the reaction with Ellman's reagent, we estimated the concentration of oxidized thiol groups. Additionally, we measured the level of lipid peroxidation. RESULTS: In plasma drawn from MS patients, we observed a significantly higher level of 3-NT (92%; P < 0.0003), carbonyl groups (29%; P < 0.0001) and thiobarbituric acid reactive substances (73%; P < 0.0001), as well as a lower concentration of thiol groups (33%; P < 0.0001), in comparison to healthy subjects. We noted positive correlations between the level of carbonyl groups or 3-NT and both diagnostic parameters, EDSS and BDI. Negative correlations were observed between concentration of -SH groups and EDSS and BDI. CONCLUSION: Our results indicate that impaired red-ox balance can significantly promote neurodegeneration in secondary progressive MS.

Extremely low frequency electromagnetic field (ELF-EMF) reduces oxidative stress and improves functional and psychological status in ischemic stroke patients.

As a result of ischaemia/reperfusion, massive generation of reactive oxygen species occurs, followed by decreased activity of antioxidant enzymes. Extremely low frequency electromagnetic fields (ELF-EMF) can modulate oxidative stress, but there are no clinical antioxidant studies in brain stroke patients. The aim of our study was to investigate the effect of ELF-EMF on clinical and antioxidant status in post-stroke patients. Fifty-seven patients were divided into two groups: ELF-EMF and non-ELF-EMF. Both groups underwent the same 4-week rehabilitation program. Additionally, the ELF-EMF group was exposed to an ELF-EMF field of 40 Hz, 7 mT for 15 min/day for 4 weeks (5 days a week). The activity of catalase and superoxide dismutase was measured in hemolysates, and total antioxidant status (TAS) determined in plasma. Functional status was assessed before and after the series of treatments using Activities of Daily Living (ADL), Mini-Mental State Examination (MMSE), and Geriatric Depression Scale (GDS). Applied ELF-EMF significantly increased enzymatic antioxidant activity; however, TAS levels did not change in either group. Results show that ELF-EMF induced a significant improvement in functional (ADL) and mental (MMSE, GDS) status. Clinical parameters had positive correlation with the level of enzymatic antioxidant protection. Bioelectromagnetics. 38:386-396, 2017. © 2017 Wiley Periodicals, Inc.

[The inflammatory processes in atherogenesis]. / Procesy zapalne w aterogenezie.

Atherogenesis is the process of atherosclerotic plaque formation, leading to coronary artery heart disease. This process involves immune cells, mainly T and B cells, monocytes and macrophages. The process of atherogenesis is induced by inflammatory damage of endothelial cells. The characteristic construction features of the atherosclerotic plaque is a predisposing factor for acute coronary syndromes. The accumulation of inflammatory cells in the artery inner membrane enhances the local inflammatory process due to the secretion of reactive oxygen species, inflammatory cytokines and metalloproteinases, which accelerate the development of atherosclerotic lesions in the arteries. In chronic inflammation of endothelial cells, which is atherosclerosis, there is a decrease in the concentration of elastin and collagen as a result of the increased apoptosis of smooth muscle cells of the intima. This reduces the integrity and strength of the fibrous cap that covers a layer of thrombogenic plaque from contact with blood elements. Permanent inflammation promotes the formation of necrotic core, composed of dead smooth muscle cells, macrophages and foam cells formed by phagocytosis of oxidized lipid molecules. The thin fibrous cap and a large necrotic core are the cause of plaque rupture and thrombus formation within the coronary artery.

Flow cytometric analysis reveals the high levels of platelet activation parameters in circulation of multiple sclerosis patients.

The epidemiological studies confirm an increased risk of cardiovascular disease in multiple sclerosis, especially prothrombotic events directly associated with abnormal platelet activity. The aim of our study was to investigate the level of blood platelet activation in the circulation of patients with chronic phase of multiple sclerosis (SP MS) and their reactivity in response to typical platelets' physiological agonists. We examined 85 SP MS patients diagnosed according to the revised McDonald's criteria and 50 healthy volunteers as a control group. The platelet activation and reactivity were assessed using flow cytometry analysis of the following: P-selectin expression (CD62P), activation of GP IIb/IIIa complex (PAC-1 binding), and formation of platelet microparticles (PMPs) and platelet aggregates (PA) in agonist-stimulated (ADP, collagen) and unstimulated whole blood samples. Furthermore, we measured the level of soluble P-selectin (sP-selectin) in plasma using ELISA method, to evaluate the in vivo level of platelet activation, both in healthy and SP MS subjects. We found a statistically significant increase in P-selectin expression, GP IIb/IIIa activation, and formation of PMPs and PA, as well as in unstimulated and agonist-stimulated (ADP, collagen) platelets in whole blood samples from patients with SP MS in comparison to the control group. We also determined the higher sP-selectin level in plasma of SP MS subjects than in the control group. Based on the obtained results, we might conclude that during the course of SP MS platelets are chronically activated and display hyperreactivity to physiological agonists, such as ADP or collagen.