Hypercholesterolemia triggers innate immune imbalance and transforms brain infarcts after ischemic stroke DOI Creative Commons
Ali Ata Tuz,

Nils Hoerenbaum,

Özgür Ulusoy

et al.

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 8, 2025

Post-stroke early activation of neutrophils contributes to intensive neuroinflammation and worsens disease outcomes. Other pre-existing patient conditions can modify the extent their during disease, especially hypercholesterolemia. However, whether how increased circulating cholesterol amounts change neutrophil responses very after stroke has not been studied. In this study, we investigated effect high-fat diet (HFD) induced hypercholesterolemia on outcome. Mice were fed with HFD or normal (ND) for six weeks then by transient occlusion middle cerebral artery. The receptors immune cells plasma levels cytokines analyzed using flow cytometry. amount extracellular traps (NETs) was measured citH3-DNA complex ELISA. We found that HFD-induced cholesterolemia number splenic in mice but reduced bone marrow compared sham controls. After expressed higher markers Ly6G PSGL-1 (CD162) ND mice. addition, led an expression Ly6C CD68 monocyte/macrophages (MΦ) Compared ND, proinflammatory TNF-α, IL-6, IL-23, MCP-1 Remarkably, showed NETs, brain-infiltrated neutrophils, larger infarcts existence a trigger stronger MΦ, causing deteriorating

Language: Английский

The relationship between systemic inflammation index, systemic immune-inflammatory index, and inflammatory prognostic index and 90-day outcomes in acute ischemic stroke patients treated with intravenous thrombolysis DOI Creative Commons

Fei Ma,

Lulu Li, Liang Xu

et al.

Journal of Neuroinflammation, Journal Year: 2023, Volume and Issue: 20(1)

Published: Sept. 30, 2023

To explore the association of systemic inflammatory index (SIRI), immune-inflammatory (SII) and prognosis (IPI) with 90d outcomes in patients acute ischemic stroke (AIS) after intravenous thrombolysis.The who underwent thrombolysis were enrolled present study from September 2019 to December 2022. According relevant blood indexes obtained 24 h admission, corresponding values SIRI, SII IPI calculated. The correlation among SII, IPI, admission NIHSS scores was examined by Spearman analysis. ROC curve analysis conducted determine optimal cut-off value their sensitivity specificity evaluate predictive on for poor prognosis. investigate whether high independent predictors within 90 days, variables P-value < 0.05 during univariate included multivariate analysis.Compared good outcome group, group had higher SII. showed that levels significantly correlated score (r = 0.338, 0.356, 0.427, respectively; Ps 0.001). Univariate Multivariate logistic regression revealed as risk factors 90-day (OR 1.09, 1.003 7.109, respectively).High are AIS undergoing thrombolysis.

Language: Английский

Citations

39
NETosis induction reflects COVID-19 severity and long COVID: insights from a 2-center patient cohort study in Israel DOI Creative Commons
Nitzan Krinsky,

Sofia Sizikov,

Sivan Nissim

et al.

Journal of Thrombosis and Haemostasis, Journal Year: 2023, Volume and Issue: 21(9), P. 2569 - 2584

Published: April 11, 2023

COVID-19 severity and its late complications continue to be poorly understood. Neutrophil extracellular traps (NETs) form in acute COVID-19, likely contributing morbidity mortality.This study evaluated immunothrombosis markers a comprehensive cohort of recovered patients, including the association NETs with long COVID.One-hundred-seventy-seven patients were recruited from clinical cohorts at 2 Israeli centers: (mild/moderate, severe/critical), convalescent (recovered COVID), along 54 non-COVID controls. Plasma was examined for platelet activation, coagulation, NETs. Ex vivo NETosis induction capability after neutrophil incubation patient plasma.Soluble P-selectin, factor VIII, von Willebrand factor, 4 significantly elevated versus Myeloperoxidase (MPO)-DNA complex levels increased only severe did not differentiate between severities or correlate thrombotic markers. strongly correlated illness severity/duration, activation markers, coagulation factors, reduced upon dexamethasone treatment recovery. Patients COVID maintained higher induction, but NET fragments, compared patients.Increased can detected COVID. appears more sensitive measurement than MPO-DNA differentiating disease Ongoing may provide insights into pathogenesis serve as surrogate marker persistent pathology. This emphasizes need explore neutrophil-targeted therapies chronic COVID-19.

Language: Английский

Citations

34
Platelet–Neutrophil Crosstalk in Thrombosis DOI Open Access
Laura J. Mereweather, Adela Constantinescu‐Bercu, James T. B. Crawley

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(2), P. 1266 - 1266

Published: Jan. 9, 2023

Platelets are essential for the formation of a haemostatic plug to prevent bleeding, while neutrophils guardians our immune defences against invading pathogens. The interplay between platelets and innate immunity, subsequent triggering activation coagulation is part host system systemic spread pathogen in blood stream. Aberrant immunothrombosis excessive inflammation can however, contribute thrombotic burden observed many cardiovascular diseases. In this review, we highlight how interact with each other their crosstalk central both arterial venous thrombosis COVID-19. While targeting enables efficient antithrombotic treatments, they often accompanied bleeding risk. We also discuss novel approaches reduce platelet-mediated recruitment could represent promising therapies treat without affecting haemostasis.

Language: Английский

Citations

33
Neutrophil extracellular traps in central nervous system pathologies: A mini review DOI Creative Commons
Areez Shafqat, Ahmed Noor Eddin, Ghaith Adi

et al.

Frontiers in Medicine, Journal Year: 2023, Volume and Issue: 10

Published: Feb. 17, 2023

Neutrophils are the first cells to be recruited sites of acute inflammation and contribute host defense through phagocytosis, degranulation neutrophil extracellular traps (NETs). rarely found in brain because highly selective blood-brain barrier (BBB). However, several diseases disrupt BBB cause neuroinflammation. In this regard, neutrophils NETs have been visualized after various insults, including traumatic (traumatic injury spinal cord injury), infectious (bacterial meningitis), vascular (ischemic stroke), autoimmune (systemic lupus erythematosus), neurodegenerative (multiple sclerosis Alzheimer’s disease), neoplastic (glioma) causes. Significantly, preventing trafficking into central nervous system or NET production these alleviates pathology improves neurocognitive outcomes. This review summarizes major studies on contribution (CNS) disorders.

Language: Английский

Citations

31
Resolvin D1 reprograms energy metabolism to promote microglia to phagocytize neutrophils after ischemic stroke DOI Creative Commons
Lei Li,

Shu-qi Cheng,

Yuqin Sun

et al.

Cell Reports, Journal Year: 2023, Volume and Issue: 42(6), P. 112617 - 112617

Published: June 1, 2023

Neutrophil aggregation and clearance are important factors affecting neuroinflammatory injury during acute ischemic stroke. Emerging evidence suggests that energy metabolism is essential for microglial functions, especially phagocytosis, which determines the degree of brain injury. Here, we demonstrate Resolvin D1 (RvD1), a lipid mediator derived from docosahexaenic acid (DHA), promotes phagocytosis neutrophils by microglia, thereby reducing neutrophil accumulation in alleviating neuroinflammation brain. Further studies reveal RvD1 reprograms glycolysis to oxidative phosphorylation (OXPHOS), providing sufficient phagocytosis. Moreover, enhances glutamine uptake stimulates glutaminolysis support OXPHOS boost ATP production depending on adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) activation. Overall, our results promote after These findings may guide perspectives stroke therapy modulating immunometabolism.

Language: Английский

Citations

30
Novel mechanisms of thrombo-inflammation during infection: spotlight on neutrophil extracellular trap-mediated platelet activation DOI Creative Commons
Martina Colicchia, Gina Perrella, P. W. GANT

et al.

Research and Practice in Thrombosis and Haemostasis, Journal Year: 2023, Volume and Issue: 7(2), P. 100116 - 100116

Published: Feb. 1, 2023

Language: Английский

Citations

28
Blood–brain crosstalk: the roles of neutrophils, platelets, and neutrophil extracellular traps in neuropathologies DOI
Ming‐Li Chou, Abdulkareem O. Babamale, Tara L. Walker

et al.

Trends in Neurosciences, Journal Year: 2023, Volume and Issue: 46(9), P. 764 - 779

Published: July 25, 2023

Language: Английский

Citations

27
Neutrophils’ Contribution to Periodontitis and Periodontitis-Associated Cardiovascular Diseases DOI Open Access
Barbara Bassani, Martina Cucchiara, Andrea Butera

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(20), P. 15370 - 15370

Published: Oct. 19, 2023

Neutrophils represent the primary defense against microbial threats playing a pivotal role in maintaining tissue homeostasis. This review examines multifaceted involvement of neutrophils periodontitis, chronic inflammatory condition affecting supporting structures teeth summarizing contribution neutrophil dysfunction periodontitis and periodontal-related comorbidities. Periodontitis, pathological promoted by dysbiosis oral microbiota, is characterized inflammation gingiva subsequent destruction. are among first immune cells recruited to site infection, releasing antimicrobial peptides, enzymes, reactive oxygen species eliminate pathogens. The persistent state can lead aberrant activation sustained release proinflammatory mediators, finally resulting damage, bone resorption, disease progression. Growing evidence now points correlation between systemic Indeed, complexes, oxidative stress neutrophils, bridge gap local immunity, thus highlighting as key players linking periodontal conditions, including cardiovascular diseases, diabetes mellitus, rheumatoid arthritis. underscores crucial pathogenesis complex link dysfunction, inflammation, A comprehensive understanding development their impact on comorbidities holds significant implications for management health. Furthermore, it highlights need novel approaches aimed at limiting recruitment also reducing broader health contexts, offering promising avenues improved patient care.

Language: Английский

Citations

26
Neutrophil extracellular traps mediated by platelet microvesicles promote thrombosis and brain injury in acute ischemic stroke DOI Creative Commons

Xin Gao,

Xinyi Zhao, Jiacheng Li

et al.

Cell Communication and Signaling, Journal Year: 2024, Volume and Issue: 22(1)

Published: Jan. 17, 2024

Abstract Aims Neutrophil extracellular traps (NETs) have been implicated in thrombotic diseases. There is no definitive explanation for how NETs form during acute ischemic strokes (AIS). The purpose of our study was to investigate the potential mechanism and role formation AIS process. Methods As well as 45 healthy subjects, patients with had ELISA tests performed detect NET markers. Expression high-mobility group box 1 (HMGB1) on platelet microvesicles (PMVs) analyzed by flow cytometry subjects patients’ blood samples. We established middle cerebral artery occlusion (MCAO) mice model elucidate interaction between PMPs NETs. Results A significant elevation markers found patient plasma patients, neutrophils generated more from neutrophils. HMGB1 expression upregulated PMVs induced formation. enhanced Procoagulant activity (PCA) through tissue factor via activation. Targeting lactadherin genetical pharmacology could regulate MCAO model. Conclusions mediated derived exacerbate thrombosis brain injury AIS.

Language: Английский

Citations

16
Stroke and myocardial infarction induce neutrophil extracellular trap release disrupting lymphoid organ structure and immunoglobulin secretion DOI Creative Commons
Ali Ata Tuz, Susmita Ghosh,

Laura Karsch

et al.

Nature Cardiovascular Research, Journal Year: 2024, Volume and Issue: 3(5), P. 525 - 540

Published: April 23, 2024

Post-injury dysfunction of humoral immunity accounts for infections and poor outcomes in cardiovascular diseases. Among immunoglobulins (Ig), IgA, the most abundant mucosal antibody, is produced by plasma B cells intestinal Peyer's patches (PP) lamina propria. Here we show that patients with stroke myocardial ischemia (MI) had strongly reduced IgA blood levels. This was phenocopied experimental mouse models where decreased fecal were accompanied rapid loss IgA-producing PP Reduced IgG detectable mice 3-10 d after injury. Stroke/MI triggered release neutrophil extracellular traps (NETs). Depletion neutrophils, NET degradation or blockade inhibited

Language: Английский

Citations

15