Stroke Mechanism Research Articles

Lactylation and Ischemic Stroke: Research Progress and Potential Relationship.

Ischemic stroke is caused by interrupted cerebral blood flow and is a leading cause of mortality and disability worldwide. Significant advancements have been achieved in comprehending the pathophysiology of stroke and the fundamental mechanisms responsible for ischemic damage. Lactylation, as a newly discovered post-translational modification, has been reported to participate in several physiological and pathological processes. However, research on lactylation and ischemic stroke is scarce. This review summarized the current function of protein lactylation in other diseases or normal physiological processes and explored their potential link with the pathophysiological process and the reparative mechanism of ischemic stroke. We proposed that neuroinflammation, regulation of metabolism, regulation of messenger RNA translation, angiogenesis, and neurogenesis might be the bridge linking lactylation and ischemic stroke. Our study provided a novel perspective for comprehending the role of protein lactylation in the pathophysiological processes underlying ischemic stroke. Lactylation might be a promising target in drug development of ischemic stroke.

Abstract 4123899: Stroke Risk in Patients with an Isolated Interventricular Membranous Septal Aneurysm

Aim: This study investigates the prevalence of isolated interventricular membranous septal (IVMS) aneurysms detected via echocardiography and assesses the associated stroke risk without other classical risk factors. Methods: We searched the echocardiography database at Mount Sinai Morningside from January 2017 to September 2023. Identified echocardiograms were reviewed to confirm IVMS aneurysms and exclude sinus of Valsalva aneurysms. Patients with concurrent structural heart anomalies were excluded. Medical records were examined for baseline characteristics, risk factors, and cortical brain infarcts. Results: From 51,732 subjects, 18 were identified with IVMS aneurysms, yielding a prevalence of 0.04%. Four patients with significant structural heart disease were excluded, resulting in a final sample size of 14. Of these, 9 (64%) were female with a mean age of 59.6, and 5 (36%) were male with a mean age of 55.4. The mean BMI was 27.9 kg/m 2 , with 4 classified as obese. All patients were nonsmokers; 2 had a family history of stroke. One patient had diabetes, 8 had hyperlipidemia, and 9 had hypertension. Only one patient had paroxysmal atrial fibrillation, with a CHA2DS2-VASc score of 0. Echocardiography revealed structurally normal hearts with a mean left ventricular ejection fraction of 61% and a mean left atrial volume index of 24.8 mL/m 2 . The mean neck diameter of the aneurysm was 8.7 mm, and the mean diameter was 11.9 mm. Two patients had inter-atrial septal aneurysms, and one had a patent foramen ovale. Out of the 14 patients, 5 had a history of ischemic stroke (4) or transient ischemic attacks (1), all of whom were 64 years or younger with a mean RoPE Score of 6 and a mean CHA2DS2-VASc score of 1.6 at the time of their first neurologic event. All patients were treated with aspirin and statin therapy. Two patients had recurrent strokes, one of whom had four recurrent strokes, all cortical infarcts. These patients were switched to clopidogrel after 3 months of dual antiplatelet therapy. No anticoagulation was used. Conclusion: This retrospective study highlights a notable association between isolated IVMS aneurysms and an increased risk of ischemic stroke (36%) and recurrent ischemic stroke (14%). Despite their rarity, these anomalies should be considered in unexplained strokes. Optimal management strategies remain ambiguous, but anticoagulation may be favored based on presumed stroke mechanisms. Large-scale multicenter studies are needed for validation.

Macrophage exosomal miR-30c-2-3p in atherosclerotic plaques aggravates microglial neuroinflammation during large-artery atherosclerotic stroke via TGF-β/SMAD2 pathway

Circulating miR-30c-2-3p has been closely related to vascular diseases, however, its role and underlying mechanisms in ischemic stroke remained unclear. Our study addressed this gap by observing elevated levels of exosomal miR-30c-2-3p in patients with acute ischemic stroke due to large artery atherosclerosis. Further investigation revealed that these exosomal miR-30c-2-3p primarily originated from macrophages within atherosclerotic plaques, exacerbating ischemic stroke by targeting microglia. Exosomes enriched with miR-30c-2-3p increased microglial inflammatory properties in vivo and aggravated neuroinflammation by inhibiting SMAD2. In summary, our findings revealed a novel mechanism whereby macrophage-derived foam cells within atherosclerotic plaques secrete exosomes with high levels of miR-30c-2-3p, thus aggravate brain damage during ischemic stroke, which serves as crucial link between the periphery and brain.

VEGFD/VEGFR3 signaling contributes to the dysfunction of the astrocyte IL-3/microglia IL-3Rα cross-talk and drives neuroinflammation in mouse ischemic stroke.

Astrocyte-derived IL-3 activates the corresponding receptor IL-3Rα in microglia. This cross-talk between astrocytes and microglia ameliorates the pathology of Alzheimer's disease in mice. In this study we investigated the role of IL-3/IL-3Rα cross-talk and its regulatory mechanisms in ischemic stroke. Ischemic stroke was induced in mice by intraluminal occlusion of the right middle cerebral artery (MCA) for 60 min followed by reperfusion (I/R). Human astrocytes or microglia subjected to oxygen-glucose deprivation and reoxygenation (OGD/Re) were used as in vitro models of brain ischemia. We showed that both I/R and OGD/Re significantly induced decreases in astrocytic IL-3 and microglial IL-3Rα protein levels, accompanied by pro-inflammatory activation of A1-type astrocytes and M1-type microglia. Importantly, astrocyte-derived VEGFD acting on VEGFR3 of astrocytes and microglia contributed to the cross-talk dysfunction and pro-inflammatory activation of the two glial cells, thereby mediating neuronal cell damage. By using metabolomics and multiple biochemical approaches, we demonstrated that IL-3 supplementation to microglia reversed OGD/Re-induced lipid metabolic reprogramming evidenced by upregulated expression of CPT1A, a rate-limiting enzyme for the mitochondrial β-oxidation, and increased levels of glycerophospholipids, the major components of cellular membranes, causing reduced accumulation of lipid droplets, thus reduced pro-inflammatory activation and necrosis, as well as increased phagocytosis of microglia. Notably, exogenous IL-3 and the VEGFR antagonist axitinib reestablished the cross-talk of IL-3/IL-3Rα, improving microglial lipid metabolic levels via upregulation of CPT1A, restoring microglial phagocytotic function and attenuating microglial pro-inflammatory activation, ultimately contributing to brain recovery from I/R insult. Our results demonstrate that VEGFD/VEGFR3 signaling contributes to the dysfunction of the astrocyte IL-3/microglia IL-3Rα cross-talk and drives pro-inflammatory activation, causing lipid metabolic reprogramming of microglia. These insights suggest VEGFR3 antagonism or restoring IL-3 levels as a potential therapeutic strategy for ischemic stroke.

A potential role of gut microbiota in stroke: mechanisms, therapeutic strategies and future prospective.

Neurological conditions like Stroke and Alzheimer's disease (AD) often include inflammatory responses in the nervous system. Stroke, linked to high disability and mortality rates, poses challenges related to organ-related complications. Recent focus on understanding the pathophysiology of ischemic stroke includes aspects like cellular excitotoxicity, oxidative stress, cell death mechanisms, and neuroinflammation. The objective of this paper is to summarize and explore the pathophysiology of ischemic stroke, elucidates the gut-brain axis mechanism, and discusses recent clinical trials, shedding light on novel treatments and future possibilities. Changes in gut architecture and microbiota contribute to dementia by enhancing intestinal permeability, activating the immune system, elevating proinflammatory mediators, altering blood-brain barrier (BBB) permeability, and ultimately leading to neurodegenerative diseases (NDDs). The gut-brain axis's potential role in disease pathophysiology offers new avenues for cell-based regenerative medicine in treating neurological conditions. In conclusion, the gut microbiome significantly impacts stroke prognosis by highlighting the role of the gut-brain axis in ischemic stroke mechanisms. This insight suggests potential therapeutic strategies for improving outcomes.

PI3K/AKT signaling and neuroprotection in ischemic stroke: molecular mechanisms and therapeutic perspectives.

It has been reported that the PI3K/AKT signaling pathway plays a key role In the pathogenesis of ischemic stroke. As a result, the development of drugs targeting the PI3K/AKT signaling pathway has attracted increasing attention from researchers. This article reviews the pathological mechanisms and advancements in research related to the signaling pathways in ischemic stroke, with a focus on the PI3K/AKT signaling pathway.The key findings include the following: (1) The complex pathological mechanisms of ischemic stroke can be categorized into five major types: excitatory amino acid toxicity, Ca2+ overload, inflammatory response, oxidative stress, and apoptosis. (2) The PI3K/AKT-mediated signaling pathway is closely associated with the occurrence and progression of ischemic stroke, which primarily involves the NF-kB, NRF2, BCL-2, mTOR, and endothelial NOS signaling pathways. (3) Natural products, including flavonoids, quinones, alkaloids, phenylpropanoids, phenols, terpenoids, and iridoids, show great potential as candidate substances for the development of innovative anti-stroke medications. (4) Recently, novel therapeutic techniques, such as electroacupuncture and mesenchymal stem cell therapy, have demonstrated the potential to improve stroke outcomes by activating the PI3K/AKT signaling pathway, providing new possibilities for the treatment and rehabilitation of patients with ischemic stroke. Future investigations should focus on the direct regulatory mechanisms of drugs targeting the PI3K/AKT signaling pathway and their clinical translation to develop innovative treatment strategies for ischemic stroke.

Prognosis of Proximal and Distal Vertebrobasilar Artery Stent Placement.

Vertebrobasilar artery stent placement (VBS) is potentially effective in preventing recurrent posterior circulation strokes; however, the incidences of in-stent restenosis and stented-territory ischemic events based on the location of stent placement have rarely been investigated. We aimed to investigate the characteristics and prognosis of VBS between intracranial and extracranial. This study was single-center retrospective cohort study, and we obtained medical records of patients who underwent VBS. We compared clinical and periprocedural factors between extracranial and intracranial VBS. The primary outcomes included the incidence of in-stent restenosis (>50% reduction in lumen diameter) and stented-territory ischemic events. We compared the incidence of in-stent restenosis and stented-territory ischemic events by using Kaplan-Meier curves. Of the 105 patients, 41 (39.0%) underwent extracranial VBS, and 64 (61.0%) underwent intracranial VBS. During the follow-up, the incidences of in-stent restenosis and stented-territory ischemic events were 15.2% and 22.9%, respectively. The procedure time was longer (47.7 ± 19.5 minutes versus 74.5 ± 35.2 minutes, P < .001), and the rate of residual stenosis (≥30%) just after VBS was higher (2 [4.9%] versus 24 [37.5%], P < .001) in intracranial VBS than in extracranial VBS. Also, the incidences of in-stent restenosis were significantly higher in intracranial VBS than in extracranial VBS (4.9% versus 21.9%, P = .037). On the other hand, the incidences of stented-territory ischemic events (7.3% versus 32.8%, P < .001) were significantly higher in intracranial VBS than in extracranial VBS. The main mechanisms of stroke were artery-to-artery embolism (2 [66.7%]) in extracranial VBS, and artery-to-artery embolism (9 [42.9%]) and branch atheromatous disease (8 [38.1%]) in intracranial VBS. The Kaplan-Meier curve demonstrated a higher incidence of in-stent restenosis and stented-territory ischemic events in intracranial VBS than in extracranial VBS (P = .008 and P = .002, respectively). During the follow-up, the incidence of in-stent restenosis and stented-territory ischemic events was higher in patients with intracranial VBS than in those with extracranial VBS. The higher rates of postprocedural residual stenosis might have contributed to the increased risk of in-stent restenosis. Furthermore, prolonged procedure time and additional stroke mechanism, including branch atheromatous disease, might be associated with a higher risk of stented-territory ischemic events in intracranial VBS.

Competing stroke mechanisms despite adequate oral anticoagulant therapy: the role of transesophageal echocardiography.

Ischemic strokes in patients on oral anticoagulant therapy (OAT) despite optimal adherence pose a therapeutic challenge. We assessed the utility of transesophageal echocardiography (TEE) in identifying potential competing cardiac causes for stroke that occurred despite adequate OAT. This retrospective observational study included patients admitted for acute ischemic stroke between January 2022 and June 2023 who were on OAT for an established long-term indication. Transthoracic and transesophageal echocardiography, along with assessment of OAT adherence, were conducted. Demographic data, OAT details, and stroke characteristics were analysed to determine the influence of TEE findings on therapeutic decisions. We included 26 patients. TEE identified potential cardiac competing stroke mechanisms in 88% of cases, with valvular thrombi and left atrial or appendage thrombus being predominant. Infective endocarditis, often asymptomatic, was unexpectedly prevalent. TEE significantly influenced therapeutic decisions, especially in cases where transthoracic echocardiography was inconclusive. TEE may be crucial for unravelling the mechanisms of ischemic stroke in patients on adequate OAT, guiding precise therapeutic strategies and potentially reducing the risk of recurrent embolic events. Our findings underscore the limitations of standard echocardiography in detecting cardiac embolic sources and emphasize the importance of tailored decision-making in secondary stroke prevention.

Free DNA activates secondary stroke mechanism.

Free DNA activates secondary stroke mechanism.

Overview and Future Direction of Embolic Stroke of Undetermined Source from the Insights of CHALLENGE ESUS/CS Registry.

Cryptogenic stroke (CS) accounts for approximately one-fourth of acute ischemic strokes, with most cases derived from embolic etiologies. In 2014, embolic stroke of undetermined source (ESUS) was advocated and the efficacy of anticoagulant therapy was anticipated. However, 3 large-scale clinical trials failed to demonstrate the superiority of direct oral anticoagulants (DOACs) over aspirin, potentially due to the heterogeneous and diverse pathologies of ESUS, including paroxysmal atrial fibrillation (AF), arteriogenic sources such as nonstenotic carotid plaque and aortic complicated lesion (ACL), patent foramen oval (PFO), and nonbacterial thrombotic endocarditis (NBTE) related to active cancer.Transesophageal echocardiography (TEE) is one of the most effective imaging modalities for assessing embolic sources in ESUS and CS. The Mechanisms of Embolic Stroke Clarified by Transesophageal Echocardiography for Embolic Stroke of Undetermined Source/Cryptogenic Stroke (CHALLENGE ESUS/CS) registry is a multicenter registry that enrolled consecutive patients with CS who underwent TEE at 8 hospitals in Japan between April 2014 and December 2016. Their mean age was 68.7±12.8 years, and 455 patients (67.2%) were male. The median National Institutes of Health Stroke Scale (NIHSS) score was 2. Since 7 analyses have been conducted from each institution to date, novel and significant insights regarding embolic origins and pathophysiologies of ESUS and CS were elucidated from this multicenter registry. This review discusses the diagnosis and treatment of ESUS and CS, tracing their past and future directions. Meaningful insights from the CHALLENGE ESUS/CS registry are also referenced and analyzed.

Combined Analysis of Human and Experimental Rat Samples Identified Biomarkers for Ischemic Stroke.

The genetic transcription profile and underlying molecular mechanisms of ischemic stroke (IS) remain elusive. To address this issue, four mRNA and one miRNA expression profile of rats with middle cerebral artery occlusion (MCAO) were acquired from the Gene Expression Omnibus (GEO) database. A total of 780 differentially expressed genes (DEGs) and 56 miRNAs (DEMs) were screened. Gene set and functional enrichment analysis revealed that a substantial number of immune-inflammation-related pathways were abnormally activated in IS. Through weighted gene co-expression network analysis, the turquoise module was identified as meaningful. By taking the intersection of the turquoise module genes, DEM-target genes, and all DEGs, 354 genes were subsequently obtained as key IS-related genes. Among them, six characteristic genes were identified using the least absolute shrinkage and selection operator. After validation with three external datasets, transforming growth factor beta 1 (Tgfb1) was selected as the hub gene. This finding was further confirmed by gene expression pattern analysis in both the MCAO model rats and clinical IS patients. Moreover, the expression of the hub genes exhibited a negative correlation with the modified Rankin scale score (P < 0.05). Collectively, these results expand our knowledge of the genetic profile and molecular mechanisms involved in IS and suggest that the Tgfb1 gene is a potential biomarker of this disease.

DJ-1 regulates astrocyte activation through miR-155/SHP-1 signaling in cerebral ischemia/reperfusion injury.

Reactive astrocyte activation in the context of cerebral ischemia/reperfusion (I/R) injury gives rise to two distinct subtypes: the neurotoxic A1 type and the neuroprotective A2 type. DJ-1 (Parkinson disease protein 7, PARK7), originally identified as a Parkinson's disease-associated protein, is a multifunctional anti-oxidative stress protein with molecular chaperone and signaling functions. SHP-1 (Src homology 2 domain-containing phosphatase-1) is a protein tyrosine phosphatase closely associated with cellular signal transduction. miR-155 is a microRNA that participates in cellular functions by regulating gene expression. Recent studies have uncovered the relationship between DJ-1 and astrocyte-mediated neuroprotection, which may be related to its antioxidant properties and regulation of signaling molecules such as SHP-1. Furthermore, miR-155 may exert its effects by influencing SHP-1, providing a potential perspective for understanding the molecular mechanisms of stroke. A middle cerebral artery occlusion/reperfusion (MCAO/R) model and an oxygen-glucose deprivation/reperfusion (OGD/R) model were established to simulate focal cerebral I/R injury invivo and invitro, respectively. The invivo interaction between DJ-1 and SHP-1 has been experimentally validated through immunoprecipitation. Overexpression of DJ-1 attenuates I/R injury and suppresses miR-155 expression. In addition, inhibition of miR-155 upregulates SHP-1 expression and modulates astrocyte activation phenotype. These findings suggest that DJ-1 mediates astrocyte activation via the miR-155/SHP-1 pathway, playing a pivotal role in the pathogenesis of cerebral ischemia-reperfusion injury. Our results provide a potential way for exploring the pathogenesis of ischemic stroke and present promising targets for pharmacological intervention.

Effect of stroke etiology on treatment-related outcomes in young adults with large vessel occlusion: Results from a retrospective cohort study

IntroductionLarge vessel occlusion-acute ischemic stroke (LVO-AIS) is infrequent in young adults and exhibits distinct stroke mechanisms compared to older adults. This study sought to evaluate the impact of varying stroke etiologies on treatment-related outcomes in young adults with LVO-AIS, an aspect that remains unclear. MethodsThis retrospective cohort study included patients aged 18-50 presenting with AIS from January 2017 to December 2021 within our multi-center stroke network. Patients with LVO on CTA/MRA at presentation were included. We assessed demographics, stroke etiology (TOAST classification), and treatment-related outcomes. Based on intervention received, patients were divided into 5 groups [IV-thrombolysis (IVT) only, Mechanical Thrombectomy (MT) only, IVT+MT, no treatment, unsuccessful MT]. ResultsAmong 1210 AIS patients, 220 with LVO were included. The median age was 42 (36, 46). 75 (34.1 %) patients underwent successful MT (46.7 % received IVT+MT). 26 (11.8 %) received IVT only, 110 (50 %) received neither intervention, and 9 (4.1 %) underwent unsuccessful MT. Per TOAST, 17.4 % had large artery atherosclerosis (LAA), 19.2 % cardio-embolism, 28.6 % stroke of other etiology, and 34.7 % had undetermined etiology. Favorable thrombectomy outcomes (TICI 2b/2c/3) were observed in 87.2 %. Discharge NIH Stroke Scale (NIHSS) scores improved for patients with IVT+MT in all TOAST categories except LAA. ConclusionsYoung adults with LVO-AIS had good outcomes irrespective of stroke etiology, except LAA, which was associated with a higher discharge NIHSS. Moreover, 50 % of young adults in our study received no intervention, a quarter of those owing to delayed presentation. Further studies are needed to identify barriers in seeking acute treatment in young adults with LVO-AIS.

Stroke Measures Analysis of pRognostic Testing-Mortality nomogram predicts long-term mortality after ischemic stroke.

Predicting long-term mortality is essential for understanding prognosis and guiding treatment decisions in patients with ischemic stroke. Therefore, this study aimed to develop and validate the method for predicting 1- and 5-year mortality after ischemic stroke. We used data from the linked dataset comprising the administrative claims database of the Health Insurance Review and Assessment Service and the Clinical Research Center for Stroke registry data for patients with acute stroke within 7 days of onset. The outcome was all-cause mortality following ischemic stroke. Clinical variables linked to long-term mortality following ischemic stroke were determined. A nomogram was constructed based on the Cox's regression analysis. The performance of the risk prediction model was evaluated using the Harrell's C-index. This study included 42,207 ischemic stroke patients, with a mean age of 66.6 years and 59.2% being male. The patients were randomly divided into training (n = 29,916) and validation (n = 12,291) groups. Variables correlated with long-term mortality in patients with ischemic stroke, including age, sex, body mass index, stroke severity, stroke mechanisms, onset-to-door time, pre-stroke dependency, history of stroke, diabetes mellitus, hypertension, coronary artery disease, chronic kidney disease, cancer, smoking, fasting glucose level, previous statin therapy, thrombolytic therapy, such as intravenous thrombolysis and endovascular recanalization therapy, medications, and discharge modified Rankin Scale were identified as predictors. We developed a predictive system named Stroke Measures Analysis of pRognostic Testing-Mortality (SMART-M) by constructing a nomogram using the identified features. The C-statistics of the nomogram in the developing and validation groups were 0.806 (95% confidence interval (CI), 0.802-0.812) and 0.803 (95% CI, 0.795-0.811), respectively. The SMART-M method demonstrated good performance in predicting long-term mortality in ischemic stroke patients. This method may help physicians and family members understand the long-term outcomes and guide the appropriate decision-making process.

A Comprehensive Genetic and Bioinformatic Analysis Provides Evidence for the Engagement of COVID-19 GWAS-Significant Loci in the Molecular Mechanisms of Coronary Artery Disease and Stroke

Cardiovascular diseases (CVDs) significantly exacerbate the severity and mortality of COVID-19. We aimed to investigate whether GWAS-significant SNPs correlate with CVDs in severe COVID-19 patients. DNA samples from 199 patients with severe COVID-19 hospitalized in intensive care units were genotyped using probe-based PCR for 10 GWAS SNPs previously implicated in severe COVID-19 outcomes. SNPs rs17713054 SLC6A20-LZTFL1 (risk allele A, OR = 2.14, 95% CI 1.06–4.36, p = 0.03), rs12610495 DPP9 (risk allele G, OR = 1.69, 95% CI 1.02–2.81, p = 0.04), and rs7949972 ELF5 (risk allele T, OR = 2.57, 95% CI 1.43–4.61, p = 0.0009) were associated with increased risk of coronary artery disease (CAD). SNPs rs7949972 ELF5 (OR = 2.67, 95% CI 1.38–5.19, p = 0.003) and rs61882275 ELF5 (risk allele A, OR = 1.98, 95% CI 1.14–3.45, p = 0.01) were linked to a higher risk of cerebral stroke (CS). No associations were observed with AH. Bioinformatics analysis revealed the involvement of GWAS-significant loci in atherosclerosis, inflammation, oxidative stress, angiogenesis, and apoptosis, which provides evidence of their role in the molecular mechanisms of CVDs. This study provides novel insights into the associations between GWAS-identified SNPs and the risk of CAD and CS.

Magnetic resonance imaging features and stroke etiology of ischemic stroke in essential thrombocythemia

BackgroundVarious essential thrombocythemia (ET)-related stroke mechanisms have been proposed, including microcirculatory disturbance due to coagulopathy, vasculitis, and embolism due to thrombus formation in large vessels. However, the stroke mechanism in ET remains largely unexplored. The purpose of this study was to evaluate magnetic resonance image (MRI) features of ischemic stroke in ET and determine the potential stroke mechanism. MethodsWe retrospectively collected data from 21 acute ischemic stroke patients with ET who were admitted to two stroke centers between 2010 and 2023. ET was diagnosed according to the World Health Organization criteria. We evaluated MRI features including the diffusion-weighted image (DWI) lesion pattern, and the presence of hemorrhagic transformation and intracranial artery steno-occlusive lesion, as well as other etiological workup results. ResultsOf 21 patients, 20 exhibited multiple ischemic lesions on DWI, mainly within a single vascular territory. Cortical infarcts were observed in 19 patients. Hemorrhagic transformation occurred in 15 patients. Additionally, 15 patients had intracranial steno-occlusive arteries, which regressed to normal in 11 patients during follow-up. Out of all patients, only 2 had potential causes of stroke other than ET (1 with atrial fibrillation and 1 with intracranial atherosclerotic stenosis). The remaining 19 patients had ET as the only identified potential cause. ConclusionsMRI features, including DWI lesion pattern in ischemic stroke patients with ET, suggested embolic etiology despite the absence of major embolic sources. Intra-arterial thrombus appears to be part of the stroke mechanism related to ET and may contribute to ischemic stroke in ET.

Lipoprotein-associated phospholipase A2 activity levels is associated with artery to artery embolism in symptomatic intracranial atherosclerotic disease

BackgroundLipoprotein-associated phospholipase A2 activity (Lp-PLA2-A) is a pivotal enzyme involved in the inflammatory process and atherosclerotic plaque vulnerability. This study aimed to investigate the potential of Lp-PLA2-A as a biomarker for reflecting artery-to-artery embolism (AAE), a critical mechanism with high risk of stroke recurrence in symptomatic intracranial atherosclerotic disease (sICAD). MethodsThe current analysis included a cohort of 1,908 patients with sICAD and baseline levels of Lp-PLA2-A from the Third China National Stroke Registry (CNSR-III). The baseline Lp-PLA2-A levels were quantified centrally using an automatic enzyme assay system. Diagnosis of sICAD was made by experienced stroke neurologists based on the presence of a cerebral infarction within the territory of a stenotic (>50 %) or occluded artery, or when clinical symptoms were consistent with the diagnosis. Infarct lesions affecting the cortex serve as imaging biomarkers for stroke mechanism involving AAE.The relationship between baseline Lp-PLA2-A quartile levels and the presence of cortical infarction was analyzed using multivariate logistic regression. ResultsCompared to patients in the first Lp-PLA2-A quartile, those in the second, third and fourth quartiles demonstrated a significantly higher proportion of AAE. The proportion of patients with cortical infarction increased with rising Lp-PLA2-A quartiles, observed at 39.3 %, 47.1 %, 47.4 %, and 50.7 % for the first, second, third and fourth quartiles respectively (P for trend=0.004). Compared with the first quartile, the odds ratios (ORs) were 1.38 (95 % CI = 1.06-1.79) for the second, 1.33 (95 % CI = 1.02-1.72) for the third quartile and 1.48 (95 % CI = 1.14-1.92) for the fourth quartile. The association between higher Lp-PLA2-A and increased proportion of cortical infarction was also present in the subgroups defined by age <65 years, male, and high-sensitivity C-reactive protein ≥2 mg/L. In sensitivity analyses, the positive correlation between Lp-PLA2-A levels and proportion of cortical infarction remained consistent. ConclusionsThis research highlights the significance of Lp-PLA2-A as a biomarker for reflecting stroke mechanism in sICAD. Additional studies are warranted to explore the potential of targeting Lp-PLA2-associated inflammatory pathways as a pivotal approach in arresting the advancement of intracranial atherosclerotic stenosis and reducing the incidence of embolic strokes.

Role of Circadian Rhythm Changes on Functional Dependence Despite Successful Repercussion in Patients with Endovascular Treatment.

Increasing evidence of circadian biology may influence the physiopathologic mechanism, progression, and recovery of stroke. However, few data have shown about circadian rhythm on futile recanalization (FR) in patients treated with endovascular treatment (EVT). From 2017 to 2021, an observational cohort of acute ischemic stroke (AIS) patients with large vessel occlusion (LVO) underwent EVT was conducted. FR was defined as the failure to achieve functional independence in patients at 90 days after EVT, although the occluded vessels reached a recanalization. The effect of circadian rhythm on FR was investigated using the logistic regression model. Of 783 patients, there were 149 patients who had stroke onset between 23:00-6:59, 318 patients between 7:00-14:59, and 316 patients between 15:00-22:59. Patients suffered a stroke during 15:00-22:59 had shorter OTP (p =0.001) time, shorter OTR (p<0.001) time, higher rate of intravenous thrombolysis (p =0.001) than groups of other time intervals. The rate of FR post-EVT in patients who had a stroke between 15:00-22:59 was significantly higher than in those with stroke onset between 23:00-6:59 (p =0.017). After adjusting for confounding factors, the time of stroke occurring during 15:00-22:59 (adjusted OR [aOR], 1.652; 95%CI, 1.024-2.666, p =0.04) was an independent predictor of FR. Circadian rhythm can directly or indirectly affect the occurrence, development, and prognosis of AIS. More studies may be needed in the future to validate the results of our study and to explore the potential mechanisms behind the effects of circadian rhythms on FR.

Bibliometric and visual analyses of research on the links between stroke and exosomes from 2008 to 2023.

Exosomes, which are extracellular vesicles secreted and released from specific cells, exist widely in cell culture supernatants and various body fluids. This study aimed to analyze the research status of exosomes in stroke, and predict developmental trends via bibliometric analyses. The related literature from January 1, 2008 to January 1, 2024 was searched in the Web of Science Core Collection and 943 articles were retrieved. VOSviewer was used to visualize national cooperation and institutional cooperation. Cluster analysis of keywords and Citespace were applied for mutation analysis. Results: The analysis of 943 works of literature showed that the number of published articles has been steadily increasing since 2015. It is predicted that nearly 211 articles will be published in 2024 and 220 annually by 2028. China has the largest number of publications (473), followed by the United States (234), and Germany (61). The institution with the most publications is Henry Ford Hospital (Detroit, MI). In the keyword cluster "Exosomes and the Mechanism of Stroke: Inflammation and Apoptosis," exosomes and inflammation were identified as hotspots. "Functional recovery" was a new trend in the keyword cluster of "Angiogenesis and Functional Recovery after Stroke." China and the United States are the main forces in this field, and both countries focusing on drug treatments. The studies have been published mainly in China and United States. The findings of our bibliometric analyses of the literature may enable researchers to choose appropriate institutions, collaborators, and journals.

Identification of Blood Biomarkers in Ischemic Stroke by Integrated Analysis of Metabolomics and Proteomics.

We aimed to uncover the pathological mechanism of ischemic stroke (IS) using a combined analysis of untargeted metabolomics and proteomics. The serum samples from a discovery set of 44 IS patients and 44 matched controls were analyzed using a specific detection method. The same method was then used to validate metabolites and proteins in the two validation sets: one with 30 IS patients and 30 matched controls, and the other with 50 IS patients and 50 matched controls. A total of 105 and 221 differentially expressed metabolites or proteins were identified, and the association between the two omics was determined in the discovery set. Enrichment analysis of the top 25 metabolites and 25 proteins in the two-way orthogonal partial least-squares with discriminant analysis, which was employed to identify highly correlated biomarkers, highlighted 15 pathways relevant to the pathological process. One metabolite and seven proteins exhibited differences between groups in the validation set. The binary logistic regression model, which included metabolite 2-hydroxyhippuric acid and proteins APOM_O95445, MASP2_O00187, and PRTN3_D6CHE9, achieved an area under the curve of 0.985 (95% CI: 0.966-1) in the discovery set. This study elucidated alterations and potential coregulatory influences of metabolites and proteins in the blood of IS patients.