Quercetin improves cerebral ischemia/reperfusion injury by promoting microglia/macrophages M2 polarization via regulating PI3K/Akt/NF-κB signaling pathway

Biomedicine & Pharmacotherapy, Год журнала: 2023, Номер 168, С. 115653 - 115653

Опубликована: Окт. 7, 2023

The modulation of microglial polarization from the pro-inflammatory M1 to anti-inflammatory M2 phenotype shows promise as a therapeutic strategy for ischemic stroke. Quercetin, natural flavonoid abundant in various plants, possesses anti-inflammatory, anti-apoptotic, and antioxidant properties. Nevertheless, its effect underlying mechanism on microglia/macrophages M1/M2 treatment cerebral ischemia/reperfusion injury (CI/RI) remain poorly explored. In current study, we observed that quercetin ameliorated neurological deficits, reduced infarct volume, decreased number (CD16/32+/Iba1+), enhanced (CD206+/Iba1+) after establishing CI/RI model rats. Subsequent vivo vitro experiments indicated downregulated markers (CD86, iNOS, TNF-α, IL-1β, IL-6) upregulated (CD206, Arg-1, IL-10, TGF-β). Network pharmacology analysis molecular docking revealed PI3K/Akt/NF-κB signaling pathway emerged core pathway. Western blot confirmed phosphorylation PI3K Akt, while alleviating IκBα NF-κB both vitro. However, inhibitor LY294002 reversed effects expression key proteins primary microglia oxygen-glucose deprivation/reoxygenation (OGD/R) Collectively, our findings demonstrate facilitates by modulating CI/RI. These provide novel insights into mechanisms

Язык: Английский

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Paediatric hydrocephalus

Nature Reviews Disease Primers, Год журнала: 2024, Номер 10(1)

Опубликована: Май 16, 2024

Язык: Английский

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No‐reflow after stroke reperfusion therapy: An emerging phenomenon to be explored

CNS Neuroscience & Therapeutics, Год журнала: 2024, Номер 30(2)

Опубликована: Фев. 1, 2024

In the field of stroke thrombectomy, ineffective clinical and angiographic reperfusion after successful recanalization has drawn attention. Partial or complete microcirculatory failure achievement full patency a former obstructed large vessel, known as "no-reflow phenomenon" "microvascular obstruction," was first reported in 1960s later detected both experimental models patients with stroke. The no-reflow phenomenon (NRP) to result from intraluminal occlusions formed by blood components extraluminal constriction exerted surrounding structures vessel wall. More recently, an emerging number studies have estimated prevalence NRP following therapy, ranging 3.3% 63% depending on its evaluation methods study population. Studies also demonstrated detrimental effects infarction progress neurological outcomes. this review, we discuss research advances, underlying pathogenesis, diagnostic techniques, management approaches concerning population provide comprehensive understanding offer references for future investigations.

Язык: Английский

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Impacts of futile reperfusion and reperfusion injury in acute ischemic stroke

Brain Circulation, Год журнала: 2024, Номер 10(1), С. 1 - 4

Опубликована: Янв. 1, 2024

Acute ischemic stroke (AIS) remains to be a challenging cerebrovascular disease. The mainstay of AIS management is endovascular reperfusion therapy, including thrombectomy and thrombolysis. However, ineffective (futile) (FR) or injury (RI) can seen in significant number patients undergoing strategy. In this article, we discuss two clinically relevant concepts known as "time window" "tissue that impact the clinical outcome therapy. We also explore patient risk factors, leading FR RI well an emerging concept "no-reflow phenomenon" reperfusion. These fundamental provide insight into references for future research.

Язык: Английский

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Efficacy and safety of tirofiban in acute ischemic stroke patients with ideal reperfusion: A cohort study of LAA and CE subgroups

European Journal of Neurology, Год журнала: 2025, Номер 32(1)

Опубликована: Янв. 1, 2025

Abstract Background and Objectives Despite achieving ideal reperfusion (eTICI = 3) through endovascular treatment (EVT), some acute ischemic stroke (AIS) patients still experience poor outcomes. This study aims to evaluate the efficacy safety of tirofiban in AIS with reperfusion, focusing on its effects large artery atherosclerosis (LAA) cardioembolic (CE) stroke. Methods A total 474 from RESCUE‐BT database were included. Patients assigned either or placebo group based received. The primary outcome was favorable functional recovery at 90 days (mRS ≤2), outcomes included symptomatic intracranial hemorrhage (sICH) 90‐day mortality. Multivariable logistic regression used adjust for confounders, subgroup interaction analyses assessed tirofiban's LAA CE populations. Results In overall population that achieved Tirofiban did not improve clinical increase risk mortality incidence sICH ( p > 0.05). However, analysis indicated potential benefits higher NIHSS scores group, especially >13 (adjusted OR 4.671, 95% CI [1.545, 14.122]). No significant differences found group. Conclusions showed those above 13. Careful patient selection is recommended.

Язык: Английский

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No-reflow phenomenon following stroke recanalization therapy: Clinical assessment advances: A narrative review

Brain Circulation, Год журнала: 2023, Номер 9(4), С. 214 - 221

Опубликована: Окт. 1, 2023

The no-reflow phenomenon (NRP) after successful vascular recanalization in acute ischemic stroke (AIS) has become a major cause of poor clinical prognosis and ineffective recanalization. However, there is currently no clear definition or unified assessment method for the NRP. Therefore, it urgent to clarify evaluation criteria NRP develop new techniques so that remedial treatment can be applied AIS patients suffering from In this brief review, variety methods defining practice are presented.

Язык: Английский

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Comprehensive Meta-Analysis of Futile Recanalization in Acute Ischemic Stroke Patients Undergoing Endovascular Thrombectomy: Prevalence, Factors, and Clinical Outcomes

Life, Год журнала: 2023, Номер 13(10), С. 1965 - 1965

Опубликована: Сен. 26, 2023

Background: Futile recanalization (FR) continues to raise concern despite the success of endovascular thrombectomy (EVT) in acute ischemic stroke (AIS). Understanding prevalence FR and identifying associated factors are crucial for refining patient prognoses optimizing management strategies. Objectives: This study aims comprehensively assess pooled FR, explore diverse connected with establish association long-term clinical outcomes among AIS patients undergoing EVT. Materials Methods: Incorporating studies focusing on following EVT patients, we conducted a random-effect meta-analysis its various imaging risk linked FR. Summary estimates were compiled heterogeneity was explored. Results: Our comprehensive meta-analysis, involving 11,700 EVT, revealed significant at 51%, range 48% 54% (Effect Size [ES]: 51%; 95% Confidence Interval [CI]: 48–54%; z = 47.66; p < 0.001). Numerous demonstrated robust correlations including atrial fibrillation (Odds Ratio [OR]: 1.39, CI 1.22 1.59; 0.001), hypertension (OR 1.65, 1.41 1.92; diabetes mellitus 1.71, 1.47 1.99; previous or transient attack 1.298, 1.06 0.012), prior anticoagulant usage 1.33, 1.08 1.63; 0.007), cardioembolic strokes 1.34, 1.10 0.003), general anesthesia 1.53, 1.35 1.74; Conversely, exhibited reduced likelihoods smoking 0.66, 0.57 0.77; good collaterals 0.33, 0.23 0.49; male sex 0.87, 0.77 0.97; 0.016), intravenous thrombolysis (IVT) 0.75, 0.66 0.86; strongly increasing age (standardized mean difference [SMD] 0.49, 0.42 0.56; 0.0001), baseline systolic blood pressure (SMD 0.20, 0.13 0.27; National Institute Health Stroke Severity Score CI: 0.65 onset-to-treatment time 0.217, 0.30; onset-to-recanalization 0.38, 0.19; 0.57; glucose 0.31, 0.22 0.41; while displaying negative Alberta Program Early CT (ASPECTS) −0.37, −0.46 −0.27; Regarding outcomes, significantly increased odds symptomatic intracranial hemorrhages 7.37, 4.89 11.12; hemorrhagic transformations 2.98, 2.37 3.75; 90-day mortality 19.24, 1.57 235.18; 0.021). Conclusions: The substantial standing approximately warrants consideration. These findings underscore complexity highlight importance tailoring strategies based individual profiles.

Язык: Английский

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Stroke–heart syndrome: current progress and future outlook

Journal of Neurology, Год журнала: 2024, Номер 271(8), С. 4813 - 4825

Опубликована: Июнь 13, 2024

Stroke can lead to cardiac complications such as arrhythmia, myocardial injury, and dysfunction, collectively termed stroke-heart syndrome (SHS). These alterations typically peak within 72 h of stroke onset have long-term effects on function. Post-stroke seriously affect prognosis are the second most frequent cause death in patients with stroke. Although traditional vascular risk factors contribute SHS, other potential mechanisms indirectly induced by also been recognized. Accumulating clinical experimental evidence has emphasized role central autonomic network disorders inflammation key pathophysiological SHS. Therefore, an assessment post-stroke dysautonomia is necessary. Currently, development treatment strategies for SHS a vital but challenging task. Identifying mediators signaling pathways essential developing therapeutic targets. Therapies targeting may be promising. Remote ischemic conditioning exerts protective through humoral, nerve, immune-inflammatory regulatory mechanisms, potentially preventing In future, well-designed trials required verify its efficacy. This comprehensive review provides valuable insights future research.

Язык: Английский

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Ependymal cells: roles in central nervous system infections and therapeutic application

Journal of Neuroinflammation, Год журнала: 2024, Номер 21(1)

Опубликована: Окт. 9, 2024

Ependymal cells are arranged along the inner surfaces of ventricles and central canal spinal cord, providing anatomical, physiological immunological barriers that maintain cerebrospinal fluid (CSF) homeostasis. Based on this, studies have found alterations in gene expression, cell junctions, cytokine secretion metabolic disturbances can lead to dysfunction ependymal cells, thereby participating onset progression nervous system (CNS) infections. Additionally, exhibit proliferative regenerative potential as well secretory functions during CNS injury, contributing neuroprotection post-injury recovery. Currently, primarily focus basic investigations their morphology, function expression; however, there is a notable lack clinical translational examining molecular mechanisms by which involved disease progression. This limits our understanding infections development therapeutic applications. Therefore, this review will discuss mechanism underlying involvement infections, explore for application treatment modalities.

Язык: Английский

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The vascular Na,K-ATPase: clinical implications in stroke, migraine, and hypertension

Clinical Science, Год журнала: 2023, Номер 137(20), С. 1595 - 1618

Опубликована: Окт. 1, 2023

Abstract In the vascular wall, Na,K-ATPase plays an important role in control of arterial tone. Through cSrc signaling, it contributes to modulation Ca2+ sensitivity smooth muscle cells. This review focuses on potential implication Na,K-ATPase-dependent intracellular signaling pathways severe disorders; ischemic stroke, familial migraine, and hypertension. We propose similarity detrimental seen these pathological conditions. The includes a retrospective proteomics analysis investigating temporal changes after stroke. revealed that expression α isoforms is down-regulated days weeks following reperfusion, while downstream kinase up-regulated. These results are since previous studies have linked futile recanalization vasospasm also explores link between migraine with aura, as reduced or pharmacological inhibition leads up-regulation cerebral hypoperfusion. discusses endogenous cardiotonic steroid-like compound, ouabain, which binds initiates pathophysiology Currently, our understanding precise mechanisms governing Na,K-ATPase/cSrc regulation wall limited. Understanding essential for developing targeted treatments cerebrovascular disorders hypertension, implicated pathogenesis conditions may contribute their comorbidity.

Язык: Английский

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