Inhibition of S100A8/A9 ameliorates neuroinflammation by blocking NET formation following traumatic brain injury DOI Creative Commons

Guihong Shi,

Yiyao Cao,

Jianye Xu

et al.

Redox Biology, Journal Year: 2025, Volume and Issue: 81, P. 103532 - 103532

Published: Feb. 5, 2025

Traumatic brain injury (TBI) triggers a robust inflammatory response that is closely linked to worsened clinical outcomes. S100A8/A9, also known as calprotectin or myeloid-related protein-8/14 (MRP8/14), an alarmin primarily secreted by activated neutrophils with potent pro-inflammatory property. In this study, we explored the roles of S100A8/A9 in modulating neuroinflammation and influencing TBI outcomes, delving into underlying mechanisms. S100A8/A9-enriched were present injured tissue patients, elevated plasma levels correlated poorer neurological function. Furthermore, using mouse model, demonstrated treatment selective inhibitor Paquinimod significantly mitigated neuronal death, thereby improving prognosis mice. Mechanistically, found conjunction neutrophil activation infiltration brain, enhances reactive oxygen species (ROS) production within neutrophils, accelerating PAD4-mediated extracellular trap (NET) formation, which turn exacerbates neuroinflammation. These findings suggest amplifies neuroinflammatory responses promoting NET formation neutrophils. Inhibition effectively attenuated NET-mediated neuroinflammation; however, when PAD4 was overexpressed adenovirus, leading increased anti-inflammatory effects inhibition markedly diminished. Further experiments knockout mice confirmed reduction NETs could substantially alleviate S100A8/A9-driven Finally, established suppression mediated through AMPK/Nrf2/HO-1 signaling pathway. underscore critical pathological role emphasize need for further exploration potential therapeutic strategy TBI.

Language: Английский

Ferroptosis in brain microvascular endothelial cells mediates blood-brain barrier disruption after traumatic brain injury DOI

Jiang Fang,

Qiang Yuan,

Zhuoying Du

et al.

Biochemical and Biophysical Research Communications, Journal Year: 2022, Volume and Issue: 619, P. 34 - 41

Published: June 14, 2022

Language: Английский

Citations

30
Inhibition of neutrophil extracellular trap formation attenuates NLRP1-dependent neuronal pyroptosis via STING/IRE1α pathway after traumatic brain injury in mice DOI Creative Commons

Yiyao Cao,

Mingming Shi, Liang Liu

et al.

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: April 14, 2023

Introduction Increased neutrophil extracellular trap (NET) formation has been reported to be associated with cerebrovascular dysfunction and neurological deficits in traumatic brain injury (TBI). However, the biological function underlying mechanisms of NETs TBI-induced neuronal cell death are not yet fully understood. Methods First, tissue peripheral blood samples TBI patients were collected, infiltration was detected by immunofluorescence staining Western blot. Then, a controlled cortical impact device used model trauma mice, Anti-Ly6G, DNase, CL-amidine given reduce neutrophilic or mice evaluate function. Finally, pathway changes pyroptosis induced after investigated administration peptidylarginine deiminase 4 (a key enzyme NET formation) adenovirus inositol-requiring enzyme-1 alpha (IRE1α) inhibitors mice. Results We that both circulating biomarkers local significantly increased had positive correlations worse intracranial pressure (ICP) patients. Furthermore, depletion neutrophils effectively reduced subjected TBI. we found degradation inhibition inhibited nucleotide-binding oligomerization domain (NOD)-like receptor pyrin containing 1 (NLRP1) inflammasome-mediated TBI, whereas these inhibitory effects abolished cyclic GMP-AMP (cGAMP), an activator stimulating Interferon genes (STING). Moreover, overexpression PAD4 cortex adenoviruses could aggravate NLRP1-mediated pro-pyroptotic rescued also receiving STING antagonists. IRE1α activation upregulated promote this process. Notably, inhibitor abrogated NETs-induced NLRP1 Discussion Our findings indicated contribute promoting pyroptosis. Suppression STING/ signaling can ameliorate pyroptotic

Language: Английский

Citations

22
Multiple Metabolites Derived from Mushrooms and Their Beneficial Effect on Alzheimer’s Diseases DOI Open Access

Zijian Tong,

Guodong Chu,

Chenmeng Wan

et al.

Nutrients, Journal Year: 2023, Volume and Issue: 15(12), P. 2758 - 2758

Published: June 15, 2023

Mushrooms with edible and medicinal potential have received widespread attention because of their diverse biological functions, nutritional value, delicious taste, which are closely related to rich active components. To date, many bioactive substances been identified purified from mushrooms, including proteins, carbohydrates, phenols, vitamins. More importantly, molecules derived mushrooms show great alleviate the pathological manifestations Alzheimer’s disease (AD), seriously affects health elderly people. Compared current therapeutic strategies aimed at symptomatic improvement, it is particularly important identify natural products resource-rich that can modify progression AD. This review summarizes recent investigations multiple constituents (carbohydrates, peptides, etc.) isolated combat In addition, underlying molecular mechanisms mushroom metabolites against AD discussed. The various involved in antiAD activities include antioxidant anti-neuroinflammatory effects, apoptosis inhibition, stimulation neurite outgrowth, etc. information will facilitate application mushroom-derived treatment However, isolation new types further vivo exploration effect still required.

Language: Английский

Citations

20
Immune Response in Traumatic Brain Injury DOI Creative Commons
Eder Cáceres,

Juan Olivella,

Mario Di Napoli

et al.

Current Neurology and Neuroscience Reports, Journal Year: 2024, Volume and Issue: 24(12), P. 593 - 609

Published: Oct. 29, 2024

Abstract Purpose of Review This review aims to comprehensively examine the immune response following traumatic brain injury (TBI) and how its disruption can impact healing recovery. Recent Findings The is now considered a key element in pathophysiology TBI, with consequences far beyond acute phase after injury. A delicate equilibrium crucial for healthy When this disrupted, chronic inflammation imbalance lead detrimental effects on survival disability. Summary Globally, imposes substantial burden terms both years life lost lived Although epidemiology exhibits dynamic trends over time across regions, TBI disproportionally affects younger populations, posing psychosocial financial challenge communities families. Following initial trauma, primary succeeded by an inflammatory response, primarily orchestrated innate system. inflammasome plays pivotal role during stage, catalyzing programmed cell death pathways up-regulation cytokines transcription factors. These events trigger activation differentiation microglia, thereby intensifying systemic level facilitating migration cells edema. initially originated brain, monitored our autonomic nervous Through vagus nerve adrenergic cholinergic receptors various peripheral lymphoid organs cells, bidirectional communication regulation between systems established.

Language: Английский

Citations

7
Cordycepin enhances anti-tumor immunity in colon cancer by inhibiting phagocytosis immune checkpoint CD47 expression DOI

Qifeng Deng,

Xinrui Li,

Chunqiang Fang

et al.

International Immunopharmacology, Journal Year: 2022, Volume and Issue: 107, P. 108695 - 108695

Published: March 16, 2022

Language: Английский

Citations

27
Endoplasmic reticulum stress promotes sepsis‐induced muscle atrophy via activation of STAT3 and Smad3 DOI

Yingfang Zheng,

Hongkai Dai,

Renyu Chen

et al.

Journal of Cellular Physiology, Journal Year: 2023, Volume and Issue: 238(3), P. 582 - 596

Published: Feb. 15, 2023

Abstract Endoplasmic reticulum (ER) stress is involved in skeletal muscle atrophy various conditions, but the role of ER sepsis‐induced not well understood. In this study, we conducted experiments wild‐type (WT) mice and C/EBP homologous protein knockout (CHOP KO) to explore mechanism atrophy. Cecal ligation puncture (CLP) was used establish a mouse model sepsis. WT mice, body weight, mass, cross‐sectional area fibers CLP group both decreased significantly compared with sham group, which revealed that dramatic Additionally, sepsis activated ubiquitin‐proteasome system (UPS), accompanied by activation stress. vitro, inhibition suppressed activity E3 ubiquitin ligases alleviated myotube vivo, CHOP KO also reduced expression UPS‐mediated degradation, attenuated Deletion phosphorylation signal transducer activator transcription 3 (STAT3) Smad3, STAT3 Smad3 partly proteolysis caused vitro. These findings confirm activates promotes atrophy, achieved activating Smad3.

Language: Английский

Citations

14
ASK1-K716R reduces neuroinflammation and white matter injury via preserving blood–brain barrier integrity after traumatic brain injury DOI Creative Commons

Shan Meng,

Hui Cao, Yichen Huang

et al.

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

Published: Oct. 24, 2023

Traumatic brain injury (TBI) is a significant worldwide public health concern that necessitates attention. Apoptosis signal-regulating kinase 1 (ASK1), key player in various central nervous system (CNS) diseases, has garnered interest for its potential neuroprotective effects against ischemic stroke and epilepsy when deleted. Nonetheless, the specific impact of ASK1 on TBI underlying mechanisms remain elusive. Notably, mutation ATP-binding sites, such as lysine residues, can lead to catalytic inactivation ASK1. To address these knowledge gaps, we generated transgenic mice harboring site-specific mutant Map3k5-e (K716R), enabling us assess elucidate following TBI.We employed CRIPR/Cas9 generate mouse model carrying ASK1-K716R mutation, aming investigate functional implications this mutant. The controlled cortical method was utilized induce TBI. Expression distribution were detected through Western blotting immunofluorescence staining, respectively. activity after by kit. Cerebral microvessels isolated gradient centrifugation using dextran. Immunofluorescence staining performed evaluate blood-brain barrier (BBB) damage. BBB ultrastructure visualized transmission electron microscopy, while expression levels endothelial tight junction proteins signaling pathway blotting. TBI-induced neuroinflammation, conducted quantitative real-time polymerase chain reaction (qRT-PCR) flow cytometry analyses. Additionally, electrophysiological compound action potentials gray white matter injury. Finally, sensorimotor function cognitive assessed battery behavioral tests.The significantly decreased confirmed effectively inhibited phosphorylation ASK1, JNKs, p38 response demonstrated protective maintaining integrity suppressing ASK1/JNKs cells, thereby reducing degradation Besides, suppressed infiltration peripheral immune cells into parenchyma, number proinflammatory-like microglia/macrophages, increased anti-inflammatory-like downregulated several proinflammatory factors. Furthermore, attenuated improved nerve conduction both myelinated unmyelinated fibers our findings exhibited favorable long-term histological outcomes aftermath TBI.ASK1-K716R preserves inhibiting consequently proteins. it alleviates early neuroinflammation parenchyma modulating polarization microglia/macrophages. These beneficial subsequently result reduction promote recovery neurological

Language: Английский

Citations

14
Fluvoxamine Confers Neuroprotection via Inhibiting Infiltration of Peripheral Leukocytes and M1 Polarization of Microglia/Macrophages in a Mouse Model of Traumatic Brain Injury DOI
Mingming Shi, Liang Mi,

Fanjian Li

et al.

Journal of Neurotrauma, Journal Year: 2022, Volume and Issue: 39(17-18), P. 1240 - 1261

Published: May 3, 2022

Neuroinflammation is an important mediator of secondary injury pathogenesis that exerts dual beneficial and detrimental effects on pathophysiology the central nervous system (CNS) after traumatic brain (TBI). Fluvoxamine a serotonin selective reuptake inhibitor (SSRI) has been reported to have anti-inflammatory properties. However, mechanisms therapeutic fluvoxamine in neuroinflammation TBI not be defined. In this study, we showed inhibited peripheral immune cell infiltration glia activation at 3 days mice subjected TBI. treatment promoted microglial/macrophage phenotypic transformation from pro-inflammatory M1-phenotype M2-phenotype vivo vitro experiments. addition, attenuated neuronal apoptosis, blood-brain barrier (BBB) disruption, cerebrovascular damage, post-traumatic edema formation, thereby improving neurological function These findings support clinical evaluation as neuroprotective therapy for

Language: Английский

Citations

22
TGF-β1 ameliorates BBB injury and improves long-term outcomes in mice after ICH DOI Creative Commons
Huimei Wen,

Jiaying Tan,

Mi Tian

et al.

Biochemical and Biophysical Research Communications, Journal Year: 2023, Volume and Issue: 654, P. 136 - 144

Published: March 6, 2023

Intracerebral hemorrhage (ICH) is a devastating subtype of stroke characterized by high mortality and morbidity rates with no effective treatment. TGF-β/ALK-5 signaling reported to participated in the regulation blood-brain barrier (BBB) integrity inflammation pain model, effects transforming growth factor (TGF)-β1 potential mechanisms on BBB after ICH have not been fully elucidated. Herein, we demonstrated that peripheral administration TGF-β1 reduces brain edema ameliorated injury ICH. Consistent previous results, shown promote activation anti-inflammatory microglia reduce inflammatory response Furthermore, improves long-term outcomes Our data suggest may be promising therapeutic agent for

Language: Английский

Citations

11
Research progress of neuroinflammation-related cells in traumatic brain injury: A review DOI Creative Commons
Qinghui Zhao, Huige Li, Hongru Li

et al.

Medicine, Journal Year: 2023, Volume and Issue: 102(25), P. e34009 - e34009

Published: June 23, 2023

Neuroinflammation after traumatic brain injury (TBI) is related to chronic neurodegenerative diseases and one of the causes acute secondary TBI. Therefore, it particularly important clarify role cellular mechanisms in neuroinflammatory response The objective this article understand involvement cells during TBI inflammatory (for instance, astrocytes, microglia, oligodendrocytes) shed light on recent progress stimulation interaction granulocytes lymphocytes, provide a novel approach for clinical research. We searched articles PubMed published between 1950 2023, using following keywords: TBI, neuroinflammation, cells, neuroprotection, clinical. Articles inclusion paper were finalized based their novelty, representativeness, relevance main arguments review. found that includes activation glial release mediators brain, recruitment peripheral immune cells. These responses not only induce damage, but also have repairing nervous system some extent. However, all cell-to-cell interactions been well studied. After treatment cannot simply suppress response, phenotype patients’ needs be defined according specific conditions injury. Clinical trials personalized inflammation regulation therapy patients should carried out order improve prognosis patients.

Language: Английский

Citations

11