Mechanisms of Autophagy in Ineffective Reperfusion After Ischemic Stroke

Journal of Neuroscience Research, Год журнала: 2025, Номер 103(1)

Опубликована: Янв. 1, 2025

ABSTRACT Despite significant advancements in achieving high recanalization rates (80%–90%) for large vessel occlusions through mechanical thrombectomy, the issue of “futile recanalization” remains a major clinical challenge. Futile occurs when over half patients fail to experience expected symptom improvement after recanalization, often resulting severe functional impairment or death. Traditionally, this phenomenon has been attributed inadequate blood flow and reperfusion injury. More recently, ongoing neuronal death reperfusion, which leads progression ischemic penumbra into core infarct, termed reperfusion.” This review explores complex role autophagy mechanisms futile following stroke, with focus on its relationship survival. We also examine regulation autophagic activity by epigenetic mechanisms. By investigating autophagy's we aim identify novel pathways precision treatment.

Язык: Английский

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Endothelial Cells and the Blood–Brain Barrier: Critical Determinants of Ineffective Reperfusion in Stroke

European Journal of Neuroscience, Год журнала: 2025, Номер 61(3)

Опубликована: Фев. 1, 2025

ABSTRACT Ineffective reperfusion remains a critical challenge in neurointerventional treatment following ischemic stroke, with the integrity of blood–brain barrier (BBB) being key determinant patient outcomes. This review explores distinctive characteristics and roles brain endothelial cells (ECs) context stroke ineffective reperfusion. We examine unique properties ECs compared to their counterparts other tissues, focusing on pathophysiological changes, functional impairments inflammatory cascades that follow stroke. Differences gene expression between those organs offer deeper insights into role neuroprotective therapies. Additionally, drawing parallels from similar ischemia–reperfusion injury profiles may inspire novel therapeutic approaches. highlights importance understanding nuanced BBB regulation, which ultimately impacts

Язык: Английский

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Advancing stroke therapy: innovative approaches with stem cell-derived extracellular vesicles

Cell Communication and Signaling, Год журнала: 2024, Номер 22(1)

Опубликована: Июль 22, 2024

Abstract Stroke is a leading cause of mortality and long-term disability globally, with acute ischemic stroke (AIS) being the most common subtype. Despite significant advances in reperfusion therapies, their limited time window associated risks underscore necessity for novel treatment strategies. Stem cell-derived extracellular vesicles (EVs) have emerged as promising therapeutic approach due to ability modulate post-stroke microenvironment facilitate neuroprotection neurorestoration. This review synthesizes current research on potential stem EVs AIS, focusing origin, biogenesis, mechanisms action, strategies enhancing targeting capacity efficacy. Additionally, we explore innovative combination therapies discuss both challenges prospects EV-based treatments. Our findings reveal that exhibit diverse effects such promoting neuronal survival, diminishing neuroinflammation, protecting blood-brain barrier, angiogenesis neurogenesis. Various strategies, including modifications cargo modifications, been developed improve efficacy EVs. Combining other treatments, therapy, cell transplantation, nanomedicine, gut microbiome modulation, holds great promise improving outcomes. However, heterogeneity need standardized protocols EV production quality control remain be addressed. represent avenue offering address limitations Further needed optimize translate benefits clinical practice, an emphasis ensuring safety, overcoming regulatory hurdles, specificity delivery target tissues. Graphical

Язык: Английский

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Normobaric Hyperoxia Combined With Endovascular Treatment Based on Temporal Gradient: A Dose-Escalation Study

Stroke, Год журнала: 2024, Номер 55(6), С. 1468 - 1476

Опубликована: Май 15, 2024

Normobaric hyperoxia (NBO) has neuroprotective effects in acute ischemic stroke. Thus, we aimed to identify the optimal NBO treatment duration combined with endovascular treatment.

Язык: Английский

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A Comprehensive Prediction Model for Futile Recanalization in AIS Patients Post-Endovascular Therapy: Integrating Clinical, Imaging, and No-Reflow Biomarkers

Aging and Disease, Год журнала: 2024, Номер unknown

Опубликована: Янв. 1, 2024

Our study aimed to construct a predictive model for identifying instances of futile recanalization in patients with anterior circulation occlusion acute ischemic stroke (AIS) who achieved complete reperfusion following endovascular therapy. We included 173 AIS attained reperfusion, as indicated by Modified Thrombolysis Cerebral Infarction (mTICI) scale score 3. approach involved thorough analysis clinical factors, imaging biomarkers, and potential no-reflow biomarkers through both univariate multivariate analyses identify predictors recanalization. The comprehensive includes factors such age, presence diabetes, admission NIHSS score, the number stent retriever passes; like poor collaterals; notably disrupted blood-brain barrier (OR 4.321, 95% CI 1.794-10.405; p = 0.001), neutrophil-to-lymphocyte ratio (NLR; OR 1.095, 1.009-1.188; 0.030), D-dimer 1.134, 1.017-1.266; 0.024). demonstrated high accuracy, C-index 0.901 (95% 0.855-0.947) 0.911 0.863-0.954) original bootstrapping validation samples, respectively. Notably, showed significantly improved performance over models that did not include evidenced an integrated discrimination improvement 8.86% 4.34%-13.39%; < 0.001) categorized reclassification 18.38% 3.53%-33.23%; 0.015). This model, which leverages could be especially beneficial healthcare settings limited resources. It provides valuable tool predicting recanalization, thereby informing decision-making. Future research explore further refinements this its application diverse settings.

Язык: Английский

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Multi-Target and Multi-Phase Adjunctive Cerebral Protection for Acute Ischemic Stroke in the Reperfusion Era

Biomolecules, Год журнала: 2024, Номер 14(9), С. 1181 - 1181

Опубликована: Сен. 20, 2024

Stroke remains the leading cause of death and disability in some countries, predominantly attributed to acute ischemic stroke (AIS). While intravenous thrombolysis endovascular thrombectomy are widely acknowledged as effective treatments for AIS, boasting a high recanalization rate, there is significant discrepancy between success revascularization mediocre clinical outcomes observed among patients with AIS. It now increasingly understood that implementation cerebral protection strategies, serving adjunctive reperfusion, can potentially improve AIS following therapy. Herein, we reviewed several promising protective methods have potential slow down infarct growth protect penumbra. We dissect underlying reasons mismatch rates moderate prognosis introduce novel concept “multi-target multi-phase protection” guide our search neuroprotective agents be administered alongside

Язык: Английский

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Prognostic Value of Fibrosis-4 in Acute Ischemic Stroke Patients Undergoing Intravenous Thrombolysis

Clinical Interventions in Aging, Год журнала: 2024, Номер Volume 19, С. 1663 - 1674

Опубликована: Окт. 1, 2024

Purpose: Although recombinant tissue plasminogen activator (rt-PA) treatment is efficient in patients with acute ischemic stroke (AIS), a significant percentage of who received rt-PA intravenous thrombolysis (IVT) do not achieve good prognosis. Therefore, the factors that affect poor prognosis IVT are needed. The Fibrosis-4 (FIB-4) index has been used as liver fibrosis biomarker. We aimed to investigate relationship between FIB-4 and functional outcomes AIS receiving IVT. Patients Methods: This study prospectively included consecutive April 2015 May 2022. collected clinical laboratory data calculated index. Clinical outcome was (mRS ≥ 3) at 3 months after Multivariate logistic regression analysis analyze association outcome. explored interactive effect dyslipidemia on outcomes, subgroup performed. Furthermore, an individualized prediction model based for established group. Results: A total 1135 were included, 41.50% had 3-month outcomes. After adjusted by other variants P value < 0.05 univariable analysis, independently associated (OR=1.420; 95% CI: 1.113– 1.812; =0.004). There interaction ( =0.036), independent maintained (OR=1.646; 1.228– 2.206; =0.001). group, FIB-4-based predictive (the AUC training validation sets 0.767 0.708, respectively), calibration -values Hosmer–Lemeshow test > 0.05), usefulness. Conclusion: risk factor dyslipidemia, which can be simple predictor their Keywords: Fibrosis-4, stroke, thrombolysis, prognosis,

Язык: Английский

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Neurological deterioration after acute ischemic stroke: A common phenomenon with important implications

Cerebrovascular Diseases, Год журнала: 2025, Номер unknown, С. 1 - 27

Опубликована: Янв. 24, 2025

Background：Neurological deterioration following acute ischemic stroke (AIS) is a common clinical phenomenon associated with poor outcomes. However, neurological can be attributed to diverse mechanisms in different contexts. Further, there still lack of standard and well-recognized definitions deterioration, which compounds the complexities challenges its early identification management deterioration. As AIS becomes increasingly common, need address after practice further improve functional outcomes becoming more urgent. Summary: To facilitate earlier recognition precise interventions, this review, we comprehensively outline evolution definition incidence various patient groups, potential underlying causes rooted multiple pathophysiological mechanisms. We highlight risk factors provide an overview scientific basis practical applications preventative therapeutic strategies. Key messages: Early patients crucial but challenging due unified assessment criteria Standardizing developing targeted strategies based on pathological pharmacological profiles are needed

Язык: Английский

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Methylprednisolone as Adjunct to Thrombectomy for Acute Intracranial Internal Carotid Artery Occlusion Stroke

JAMA Network Open, Год журнала: 2025, Номер 8(2), С. e2459945 - e2459945

Опубликована: Фев. 18, 2025

Importance Patients with acute ischemic stroke (AIS) due to intracranial internal carotid artery (ICA) occlusion often have poor functional outcomes despite undergoing endovascular thrombectomy (EVT). Objective To investigate the effectiveness and safety associated intravenous methylprednisolone as adjunctive treatment EVT for patients AIS ICA occlusion. Design, Setting, Participants This was a post hoc analysis of MARVEL randomized, double-blind, placebo-controlled clinical trial conducted from February 9, 2022, June 30, 2023, at 82 centers across China 3-month follow-up. The primary enrolled 1680 large vessel within 24 hours last known well time in ICA, first segment middle cerebral (M1), or second (M2), whom 579 had Intervention Intravenous methylprednisolone, 2 mg/kg/d (maximum dose, 160 mg) 3 days plus vs placebo EVT. Main Outcomes Measures outcome independent ambulation 90 days, defined score 0 on modified Rankin Scale (range, [no symptoms] 6 [death]). Safety included death symptomatic hemorrhage (sICH) 48 hours, decompressive hemicraniectomy relieve midline-shift pressure after Results Among (median age, 69.0 years [IQR, 59.0-76.0 years]; 338 men [58.4%]), there were 286 group 293 group. proportion who achieved 90-day significantly higher than (151 284 [53.2%] 125 [42.7%]; adjusted risk ratio [RR], 1.27 [95% CI, 1.07-1.52]; P = .007). incidence sICH lower (26 277 [9.4%] 45 290 [15.5%]; RR, 0.55 0.35-0.87]; .01). rate compared (16 [5.6%] 29 [9.9%]; 0.54 0.30-0.98]; .04). No significant difference observed mortality between groups (methylprednisolone, 92 [32.4%] placebo, 111 239 [37.9%]; 0.84 0.67-1.05]; .13). Conclusions Relevance In this secondary randomized EVT, improved ambulation. These findings suggest that use an adjunct may hold promise option Trial registration ChiCTR.org.cn Identifier: ChiCTR2100051729

Язык: Английский

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Rationale and Study Design to Assess the Efficacy and Safety of Minocycline in Patients with Moderate to Severe Acute Ischaemic Stroke (EMPHASIS)

Stroke and Vascular Neurology, Год журнала: 2025, Номер unknown, С. svn - 003577

Опубликована: Март 26, 2025

Background Inflammation and blood-brain barrier disruption may contribute to the pathogenesis of ischaemic stroke. Minocycline was shown exert anti-inflammatory effects by attenuating microglial activation protecting in preclinical studies. Previous small-scale clinical studies have suggested that minocycline a potential beneficial effect on prognosis acute However, efficacy safety patients with stroke need be further confirmed. Study aims We designed study, Efficacy Safety Patients Moderate Severe Acute Ischaemic Stroke (EMPHASIS), evaluate improving functional outcome drug Methods The EMPHASIS study is multicentre, randomised, double-blind, placebo-controlled trial aiming recruit who had within 72 hours onset, National Institutes Health Scale score between 4 25 Ia≤1 (moderate-to-severe) will randomly allocated either or placebo groups 1:1 ratio. receive (or placebo) loading dose 200 mg, subsequent 100 mg every 12 for days. All routine guideline-based treatment. primary an excellent assessed proportion modified Rankin 0–1 at 90±7 main outcomes include number symptomatic intracranial haemorrhage 24±2 6±1 Discussion first phase III investigate whether effective safe 90 days moderate-to-severe data generated provide valuable evidence anti-inflammation treatment

Язык: Английский

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