Catechin-Based Polyphenol Nanoparticles Ameliorated Ferroptosis to Alleviate Brain Injury after Intracerebral Hemorrhage DOI
Yu Zeng, Jian Li,

Zhuo Kong

et al.

ACS Applied Materials & Interfaces, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 23, 2025

Spontaneous intracerebral hemorrhagic stroke (ICH) is a highly aggressive disease, with high incidence and mortality rate. Iron deposition following ICH leads to oxidative damage motor dysfunction, significantly impacting the overall quality of life for those affected. Here, polyphenolic nanomedicine, catechin-based polyphenol nanoparticles surface-modified by thiol-terminated poly(ethylene glycol) (CNPs@PEG), was developed through polymerization self-assembly catechin, natural compound in tea. Due its potent antioxidant metal-chelating properties, CNPs@PEG effectively maintained blood-brain barrier integrity, reduced brain edema, increased survival rate mice cerebral hemorrhage markedly improved neurological deficits after ICH. Mechanistically, accomplishes this chelating iron, enhancing tissue capacity, reducing stress, inhibiting iron deposition. This approach holds promise as targeted therapeutic strategy addressing other conditions associated overload.

Language: Английский

Srs11‐92, a ferrostatin‐1 analog, improves oxidative stress and neuroinflammation via Nrf2 signal following cerebral ischemia/reperfusion injury DOI Creative Commons
Yuhua Chen, Wei He,

Hong Wei

et al.

CNS Neuroscience & Therapeutics, Journal Year: 2023, Volume and Issue: 29(6), P. 1667 - 1677

Published: Feb. 27, 2023

Ferroptosis is increasingly becoming to be considered as an important mechanism of pathological cell death during stroke, and specific exogenous ferroptosis inhibitors have the ability reverse cerebral ischemia/reperfusion injury. However, research on Srs11-92 (AA9), a ferrostatin-1 (Fer-1) analog, in preclinical studies limited.In middle artery occlusion-reperfusion (MCAO/R) mice model or oxygen-glucose deprivation/reperfusion (OGD/R) model, Fer-1, AA9, and/or ML385 were administered, brain infarct size, neurological deficits, neuronal damage, oxidative stress, neuroinflammation determined after vitro vivo.Fer-1 AA9 improved deficits MCAO/R, inhibited overloaded iron deposition, ROS accumulation, response: it also increased expression GPx4, Nrf2, HO-1 suppressed HMGB1 NF-κB p65 epicenter injured hippocampal formation. Nrf2 inhibitor reversed neuroprotective effect including stress neuroinflammation. In showed that relieved OGD/R-induced via pathway, which was impaired by primary neurons.The findings imply Fer-1 analog may suitable for further translational protection damage signal pathway-mediated stroke others diseases.

Language: Английский

Citations

61
Scutellarin attenuates oxidative stress and neuroinflammation in cerebral ischemia/reperfusion injury through PI3K/Akt-mediated Nrf2 signaling pathways DOI Creative Commons
Xueheng Xie, Handong Wang,

Wenxiu Ge

et al.

European Journal of Pharmacology, Journal Year: 2023, Volume and Issue: 957, P. 175979 - 175979

Published: Aug. 21, 2023

Cerebral ischemia/reperfusion injury (CIRI) seriously threatens human life and health. Scutellarin (Scu) exhibits neuroprotective effects, but little is known about its underlying mechanism. Therefore, we explored protective effect on CIRI the Our results demonstrated that Scu rescued HT22 cells from cytotoxicity induced by oxygen glucose deprivation/reoxygenation (OGD/R). also showed antioxidant activity promoting nuclear factor erythroid 2-related 2 (Nrf2) translocation, upregulating heme oxygenase-1 (HO-1) expression, increasing superoxide dismutase (SOD) activity, inhibiting reactive species (ROS) generation in vitro. Additionally, reduced factor-kappa B (NF-κB) levels of pro-inflammatory factors. Interestingly, these effects were abolished Nrf2 inhibition. Furthermore, infarct volume blood-brain barrier (BBB) permeability, improved sensorimotor functions depressive behaviors, alleviated oxidative stress neuroinflammation rats subjected to middle cerebral artery occlusion/reperfusion (MCAO/R). Mechanistically, Scu-induced accumulation inactivation NF-κB accompanied an enhanced level phosphorylated protein kinase (p-AKT) both vitro vivo. Pharmacologically phosphatidylinositol-3-kinase/protein (PI3K/AKT) pathway blocked translocation NF-κB, as well anti-inflammatory activities. In summary, suggest antioxidant, anti-inflammatory, through activation mediated PI3K/Akt pathway.

Language: Английский

Citations

31
Shank3 ameliorates neuronal injury after cerebral ischemia/reperfusion via inhibiting oxidative stress and inflammation DOI Creative Commons

Hongchen Zhang,

Yuan Feng,

Yanfang Si

et al.

Redox Biology, Journal Year: 2023, Volume and Issue: 69, P. 102983 - 102983

Published: Dec. 5, 2023

Shank3, a key molecule related to the development and deterioration of autism, has recently been found downregulate in murine brain after ischemia/reperfusion (I/R). Despite this discovery, however, its effects on neuronal injury mechanism underlying remain be clarified. To address this, study, based genetically modified mice models, we revealed that expression Shank3 showed time-dependent change hippocampal neurons I/R, conditional knockout (cko) resulted aggravated injuries. The protective against oxidative stress inflammation I/R were achieved through direct binding STIM1 subsequent proteasome-mediated degradation STIM1. downregulation induced phosphorylation downstream Nrf2 Ser40, which subsequently translocated nucleus, further increased antioxidant genes such as NQO1 HO-1 HT22 cells. In vivo, study confirmed double Stim1 alleviated Shank3cko mice. conclusion, present demonstrated interacts with inhibits post-I/R inflammatory response via pathway. This interaction can potentially contribute promising method for treatment.

Language: Английский

Citations

24
Minocycline‐Loaded Cerium Oxide Nanoparticles for the Enhanced Treatment of Intracerebral Hemorrhage DOI
Xiang Xu, Zhihui Han,

Dong Li

et al.

Advanced Functional Materials, Journal Year: 2024, Volume and Issue: 34(32)

Published: April 22, 2024

Abstract Inflammatory responses and neuronal ferroptosis, which are associated with abnormal accumulation of reactive oxygen species (ROS), exert crucial damaging effects on the brain after intracerebral hemorrhage (ICH). In this study, minocycline (MC)‐loaded cerium oxide nanoparticles (CeO 2 ‐MC) constructed for combined ICH treatment. Ultra‐small CeO (≈5 nm) synthesized via a high‐temperature approach exhibits powerful free‐radical scavenging iron‐chelating abilities. vitro experiments demonstrated that ‐MC effectively attenuated ROS levels in mouse microglial cells neurons following oxyhemoglobin stimulation. addition, iron chelation properties stabilizes mitochondrial membrane potential, thereby promoting anti‐inflammatory preventing ferroptosis. an (ICH) model, exhibited robust free radical capabilities ability to preserve morphology function, mitigate edema, maintain blood–brain barrier integrity by inhibiting neuroinflammation Neurobehavioral tests significantly ameliorated spatial learning sensorimotor function ICH. Consequently, general strategy using augment therapeutic efficacy MC highlights new perspective in‐depth treatment

Language: Английский

Citations

11
Subacute Neurological Improvement Predicts Favorable Functional Recovery After Intracerebral Hemorrhage: INTERACT2 Study DOI
Shoujiang You,

Danni Zheng,

Xiaoying Chen

et al.

Stroke, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 3, 2025

BACKGROUND: The frequency and prognostic significance of subacute neurological improvement (SNI) on 90-day outcomes after acute intracerebral hemorrhage are unknown. METHODS: Secondary analyses participant data from the INTERACT2 trial (second Intensive Blood Pressure Reduction in Acute Intracerebral Hemorrhage Trial). SNI included any, moderate, significant, substantial defined as ≥1, ≥2, ≥3, ≥4 points decrease, respectively, National Institutes Health Stroke Scale 24 hours to 7 days hemorrhage. Logistic regression models were used assess associations death or major disability (modified Rankin score 3–6), scores, 3–5), alone at 90 days. Data reported odds ratios 95% CIs. RESULTS: Of 2571 patients analyses, 1492 (58.0%), 1057 (41.1%), 731 (28.4%), 490 (19.1%) experienced (24 days) hemorrhage, respectively. After adjustment for key confounders, any was associated with 49%, 25%, 65% reduced (odds ratio, 0.51 [95% CI, 0.42–0.63]), 0.75 0.63–0.90]), 0.35 0.24–0.50]), Moderate, also significantly decreased relationship between study consistent most subgroups, including age baseline hematoma volume. Early intensive blood pressure-lowering treatment did not increase SNI. CONCLUSIONS: is common predicts a lower likelihood disability. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT00716079.

Language: Английский

Citations

1
Crosstalk among mitophagy, pyroptosis, ferroptosis, and necroptosis in central nervous system injuries DOI Creative Commons
Li Zhang, Zhigang Hu, Zhenxing Li

et al.

Neural Regeneration Research, Journal Year: 2023, Volume and Issue: 19(8), P. 1660 - 1670

Published: Nov. 8, 2023

Central nervous system injuries have a high rate of resulting in disability and mortality; however, at present, effective treatments are lacking. Programmed cell death, which is genetically determined form active ordered death with many types, has recently attracted increasing attention due to its functions determining the fate survival. A growing number studies suggested that programmed involved central plays an important role progression brain damage. In this review, we provide overview injuries, including pathways mitophagy, pyroptosis, ferroptosis, necroptosis, underlying mechanisms by mitophagy regulates necroptosis. We also discuss new direction therapeutic strategies targeting for treatment aim determine connection between identify therapies modulate following injury. conclusion, based on these properties effects, interventions could be developed as potential agents injury patients.

Language: Английский

Citations

20
A Promising Strategy to Treat Neurodegenerative Diseases by SIRT3 Activation DOI Open Access

Alpna Tyagi,

Subbiah Pugazhenthi

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(2), P. 1615 - 1615

Published: Jan. 13, 2023

SIRT3, the primary mitochondrial deacetylase, regulates functions of proteins including metabolic enzymes and respiratory chain components. Although SIRT3’s in peripheral tissues are well established, significance its downregulation neurodegenerative diseases is beginning to emerge. SIRT3 plays a key role brain energy metabolism provides substrate flexibility neurons. It also facilitates coupling between fuel substrate-producing fuel-consuming tissues. mediates health benefits lifestyle-based modifications such as calorie restriction exercise. deficiency associated with syndrome (MetS), precondition for obesity, diabetes, cardiovascular disease. The pure form Alzheimer’s disease (AD) rare, it has been reported coexist these aging populations. leads dysfunction, neuroinflammation, inflammation, potentially triggering factors AD pathogenesis. Recent studies have suggested that may act through multiple pathways reduce plaque formation brain. In this review, we give an overview roles physiology pathology discuss several activators can be considered potential therapeutic agents treatment dementia.

Language: Английский

Citations

17
Established and emerging techniques for the study of microglia: visualization, depletion, and fate mapping DOI Creative Commons

Bianca Caroline Bobotis,

Torin Halvorson, Micaël Carrier

et al.

Frontiers in Cellular Neuroscience, Journal Year: 2024, Volume and Issue: 18

Published: Feb. 15, 2024

The central nervous system (CNS) is an essential hub for neuronal communication. As a major component of the CNS, glial cells are vital in maintenance and regulation network dynamics. Research on microglia, resident innate immune has advanced considerably recent years, our understanding their diverse functions continues to grow. Microglia play critical roles formation synapses, myelination, responses injury, neurogenesis, inflammation, many other physiological processes. In parallel with advances microglial biology, cutting-edge techniques characterization properties have emerged increasing depth precision. Labeling tools reporter models important study morphology, ultrastructure, dynamics, but also isolation, which required glean key phenotypic information through single-cell transcriptomics emerging approaches. Strategies selective depletion modulation can provide novel insights into microglia-targeted treatment strategies neuropsychiatric neurodegenerative conditions, cancer, autoimmunity. Finally, fate mapping as tool answer fundamental questions about including origin, migration, proliferation throughout lifetime organism. This review aims comprehensive discussion these established techniques, applications microglia development, homeostasis, CNS pathologies.

Language: Английский

Citations

7
Roles of mechanosensitive ion channel PIEZO1 in the pathogenesis of brain injury after experimental intracerebral hemorrhage DOI Creative Commons
Min Qi, Ran Liu, Fan Zhang

et al.

Neuropharmacology, Journal Year: 2024, Volume and Issue: 251, P. 109896 - 109896

Published: March 13, 2024

Secondary brain injury after intracerebral hemorrhage (ICH) is the main cause of poor prognosis in ICH patients, but underlying mechanisms remain less known. The involvement Piezo1 was studied a mouse model ICH. established by injecting autologous arterial blood into basal ganglia mice. After vehicle, blocker, GsMTx4, activator, Yoda-1, or together with mannitol (tail vein injection) injected left lateral ventricle brain, level and roles neuronal injury, edema, neurological dysfunctions were determined various indicated methods. protein neurons significantly upregulated 24 h vivo (human mice). also dramatically HT22 cells (a murine neuron cell line) cultured vitro hemin treatment as an model. GsMTx4 downregulated AQP4 levels, markedly increased Bcl2 level, maintained more alive, considerably restored flow, remarkably relieved substantially decreased serum IL-6 almost fully reversed at group In contrast, Yoda-1 achieved opposite effects. conclusion, plays crucial role pathogenesis may be target for clinical

Language: Английский

Citations

6
Alternate day fasting aggravates atherosclerosis through the suppression of hepatic ATF3 in Apoe−/− mice DOI Creative Commons

Yajuan Deng,

Xiaoyu Yang,

Xueru Ye

et al.

Life Metabolism, Journal Year: 2024, Volume and Issue: 3(3)

Published: March 7, 2024

Atherosclerosis is the major contributor to cardiovascular mortality worldwide. Alternate day fasting (ADF) has gained growing attention due its metabolic benefits. However, effects of ADF on atherosclerotic plaque formation remain inconsistent and controversial in animal models. The present study was designed investigate atherosclerosis apolipoprotein E-deficient (Apoe -/- ) mice. Eleven-week-old male Apoe mice fed with Western diet (WD) were randomly grouped into ad libitum (AL) group group, aggravated both early advanced lesion formation, which might be disturbed cholesterol profiles caused by intervention. significantly altered metabolism pathways down-regulated integrated stress response (ISR) liver. hepatic expression activating transcription factor 3 (ATF3) suppressed treated hepatocyte-specific overexpression Aft3 attenuated Moreover, ATF3 could regulated Krüppel-like 6 (KLF6) expressions KLF6 cellular ISR pathway. In conclusion, aggravates progression WD. inhibits signaling pathway decreases KLF6, subsequently inhibiting expression. liver mediates deteriorated findings suggest potentially harmful when intervention applied population at high risk atherosclerosis.

Language: Английский

Citations

6