The lactate metabolism and protein lactylation in epilepsy DOI Creative Commons
Xi Kuang, Shuang Chen,

Qingmei Ye

et al.

Frontiers in Cellular Neuroscience, Journal Year: 2025, Volume and Issue: 18

Published: Jan. 14, 2025

Protein lactylation is a new form of post-translational modification that has recently been proposed. Lactoyl groups, derived mainly from the glycolytic product lactate, have linked to protein in brain tissue, which shown correlate with increased neuronal excitability. Ischemic stroke may promote glycolysis, leading lactate accumulation tissue. This heighten excitability by upregulating levels, potentially triggering post-stroke epilepsy. Although current clinical treatments for seizures advanced significantly, approximately 30% patients epilepsy remain unresponsive medication, and prevalence continues rise. study explores mechanisms epilepsy-associated death mediated metabolism lactylation. also examines potential histone deacetylase inhibitors alleviate modifying thereby offering fresh perspectives future research into pathogenesis treatment

Language: Английский

Neutrophils in COVID-19: Not Innocent Bystanders DOI Creative Commons
Ellen McKenna,

Richard Wubben,

Johana M. Isaza-Correa

et al.

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: June 1, 2022

Unusually for a viral infection, the immunological phenotype of severe COVID-19 is characterised by depleted lymphocyte and elevated neutrophil count, with neutrophil-to-lymphocyte ratio correlating disease severity. Neutrophils are most abundant immune cell in bloodstream comprise different subpopulations pleiotropic actions that vital host immunity. Unique vary their capacity to mount antimicrobial responses, including NETosis (the generation extracellular traps), degranulation de novo production cytokines chemokines. These processes play role antiviral immunity, but may also contribute local systemic tissue damage seen acute SARS-CoV-2 infection. complications such as thrombosis, respiratory distress syndrome multisystem inflammatory children. In this Progress review, we discuss anti-viral pathological roles neutrophils potential therapeutic strategies target neutrophil-mediated responses.

Language: Английский

Citations

88
Iron, ferroptosis, and ischemic stroke DOI Open Access
Jun Guo, Qing‐zhang Tuo, Peng Lei

et al.

Journal of Neurochemistry, Journal Year: 2023, Volume and Issue: 165(4), P. 487 - 520

Published: March 13, 2023

Abstract Over 30 million people suffer from the consequences of ischemic stroke. The precise molecular mechanism neuronal damage during stroke remains unclear; therefore, effective treatment post‐ischemic a critical challenge. Recently, iron has emerged as crucial factor in post‐reperfusion injuries, participating cell peroxidation, excitotoxicity, and distinctive death pathway, namely, ferroptosis. Since is tightly regulated brain important for functions, imbalance its metabolism, including overload deficiency, been shown to impact outcomes. This review summarizes current understanding pathological events associated with discusses relevant drug development. image

Language: Английский

Citations

81
Neutrophil Targeting Platform Reduces Neutrophil Extracellular Traps for Improved Traumatic Brain Injury and Stroke Theranostics DOI Creative Commons
Qingchun Mu, Kai Yao, Madiha Zahra Syeda

et al.

Advanced Science, Journal Year: 2024, Volume and Issue: 11(21)

Published: March 23, 2024

Abstract Traumatic brain injuries (TBI) and stroke are major causes of morbidity mortality in both developing developed countries. The complex heterogeneous pathophysiology TBI cerebral ischemia‐reperfusion injury (CIRI), addition to the blood‐brain barrier (BBB) resistance, is a advancement diagnostics therapeutics. Clinical data showed that severity positively correlated with number neutrophils peripheral blood sites. Furthermore, neutrophil extracellular traps (NETs) released by correlate worse outcomes impairing revascularization vascular remodeling. Therefore, targeting deliver NETs inhibitors sites reduce formation can be an optimal strategy for therapy. Herein, study designs synthesizes reactive oxygen species (ROS)‐responsive neutrophil‐targeting delivery system loaded peptidyl arginine deiminase 4 (PAD4) inhibitor, GSK484, prevent sites, which significantly inhibited neuroinflammation improved neurological deficits, survival rate CIRI. This may provide groundwork development targeted theranostics stroke.

Language: Английский

Citations

25
Smart Liposomal Nanocarrier Enhanced the Treatment of Ischemic Stroke through Neutrophil Extracellular Traps and Cyclic Guanosine Monophosphate-Adenosine Monophosphate Synthase-Stimulator of Interferon Genes (cGAS-STING) Pathway Inhibition of Ischemic Penumbra DOI

Shanbo Sun,

Wei Lv, Shengnan Li

et al.

ACS Nano, Journal Year: 2023, Volume and Issue: 17(18), P. 17845 - 17857

Published: Sept. 15, 2023

Brain inflammation is regarded as one of the leading causes that aggravates secondary brain injury and hinders prognosis ischemic stroke. After stroke, high quantities peripheral neutrophils are recruited to lesions release neutrophil extracellular traps (NETs), aggravation blood-brain barrier (BBB) damage, activation microglia, ultimate neuronal death. Herein, a smart multifunctional delivery system has been developed regulate immune disorders in brain. Briefly, Cl-amidine, an inhibitor peptidylarginine deiminase 4 (PAD4), encapsulated into self-assembled liposomal nanocarriers (C-Lipo/CA) modified by reactive oxygen species (ROS)-responsive polymers fibrin-binding peptide achieve targeting stimuli-responsive drug. In mouse model cerebral artery occlusion/reperfusion (MCAO), C-Lipo/CA can suppress NETs process (NETosis) further inhibit cyclic guanosine monophosphate-adenosine monophosphate synthase-stimulator interferon genes (cGAS-STING) pathway addition, MCAO mice treated with significantly mitigated reperfusion injury, reduction area infarction 12.1%, compared saline group about 46.7%. These results demonstrated C-Lipo/CA, which integrated microglia regulation, BBB protection, neuron survival, exerts potential therapy strategy maximize ameliorating mortality

Language: Английский

Citations

41
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
Nanozymes: Potential Therapies for Reactive Oxygen Species Overproduction and Inflammation in Ischemic Stroke and Traumatic Brain Injury DOI
Yunfan Yang, Zi-Xiang Li, Xiaochong Fan

et al.

ACS Nano, Journal Year: 2024, Volume and Issue: 18(26), P. 16450 - 16467

Published: June 19, 2024

Nanozymes, which can selectively scavenge reactive oxygen species (ROS), have recently emerged as promising candidates for treating ischemic stroke and traumatic brain injury (TBI) in preclinical models. ROS overproduction during the early phase of these diseases leads to oxidative damage, has been a major cause mortality worldwide. However, clinical application ROS-scavenging enzymes is limited by their short vivo half-life inability cross blood-brain barrier. mimic catalytic function natural enzymes, several advantages, including cost-effectiveness, high stability, easy storage. These advantages render them superior disease diagnosis therapeutic interventions. This review highlights recent advancements nanozyme applications TBI, emphasizing potential mitigate detrimental effect overproduction, inflammation, barrier compromise. Therefore, nanozymes represent treatment modality conditions future medical practices.

Language: Английский

Citations

15
FPR1 affects acute rejection in kidney transplantation by regulating iron metabolism in neutrophils DOI Creative Commons
Peiyuan Li, Wenbin Ji, Baotong Zhang

et al.

Molecular Medicine, Journal Year: 2025, Volume and Issue: 31(1)

Published: Jan. 23, 2025

Abstract Background Acute rejection (AR) is one of the significant factors contributing to poor prognosis in patients following kidney transplantation. Neutrophils are main cause early host-induced tissue injury. This paper intends investigate possible mechanisms neutrophil involvement acute renal Methods Samples were analyzed for their relationship with immune cells using CIBERSORT. WGCNA was used identify modules high relevance neutrophils and hub genes extracted. The effect on function after blocking formyl peptide receptor 1 (FPR1) tested vitro experiments. effects FPR1 as well vivo constructing a mouse transplant model. Results proportion higher AR group than non-rejection group, identified an important gene regulation transplantation by neutrophils. At cellular level, inhibited activation ERK1/2 pathway, decreased ferrous ion content, affected expression iron metabolism-related proteins, suppressed formation NETs. In model transplantation, blockade graft infiltration NETs content. Meanwhile, attenuated injury during rejection. Conclusion study found that might be molecule involved explored between neutrophils, provided potential treatment methods clinical practice.

Language: Английский

Citations

1
Siegesbeckia orientalis ethanol extract impedes RAGE-CD11b interaction driven by HMGB1 to alleviate neutrophil-involved neuronal injury poststroke DOI

Jinfen Chen,

Xingping Quan,

Yiyang Li

et al.

Phytomedicine, Journal Year: 2025, Volume and Issue: 139, P. 156541 - 156541

Published: Feb. 17, 2025

Language: Английский

Citations

1
Systemic immune responses after ischemic stroke: From the center to the periphery DOI Creative Commons
Fan Wu, Zongchi Liu, Lihui Zhou

et al.

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: Sept. 20, 2022

Ischemic stroke is a leading cause of disability and death. It imposes heavy economic burden on individuals, families society. The mortality rate ischemic has decreased with the help thrombolytic drug therapy intravascular intervention. However, nerve damage caused by ischemia-reperfusion long-lasting followed multiple organ dysfunction. In this process, immune responses manifested systemic inflammatory play an important role. begins neuroinflammation following stroke. large number cells released after activation in lesion area, along deactivated neuroendocrine autonomic nervous systems, link center periphery. With immunity emergence immunosuppression, peripheral organs become second “battlefield” response gradually dysfunctional lead to adverse prognosis. purpose review was describe We hope provide new ideas for future research clinical treatments improve patient outcomes quality life.

Language: Английский

Citations

31
Neutrophil Extracellular Traps in Cerebral Ischemia/Reperfusion Injury: Friend and Foe DOI

Haoyue Luo,

Hanjing Guo,

Yue Zhou

et al.

Current Neuropharmacology, Journal Year: 2023, Volume and Issue: 21(10), P. 2079 - 2096

Published: March 9, 2023

Cerebral ischemic injury, one of the leading causes morbidity and mortality worldwide, triggers various central nervous system (CNS) diseases, including acute stroke (AIS) chronic ischemia-induced Alzheimer's disease (AD). Currently, targeted therapies are urgently needed to address neurological disorders caused by cerebral ischemia/reperfusion injury (CI/RI), emergence neutrophil extracellular traps (NETs) may be able relieve pressure. Neutrophils precursors brain following exert complicated functions. NETs extracellularly release reticular complexes neutrophils, i.e., double-stranded DNA (dsDNA), histones, granulins. Paradoxically, play a dual role, friend foe, under different conditions, for example, physiological circumstances, infection, neurodegeneration, ischemia/reperfusion. Increasing evidence indicates that anti-inflammatory effects degrading cytokines chemokines through protease at relatively stable moderate level while excessive amounts (NETosis) irritated CI/RI exacerbate inflammatory response aggravate thrombosis, disrupt blood-brain barrier (BBB), initiates sequential neuron tissue damage. This review provides comprehensive overview machinery formation role an abnormal cascade in CI/RI, as well other diseases. Herein, we highlight potential therapeutic target against inspire translational research innovative clinical approaches.

Language: Английский

Citations

17