Outcome Of Ischemic Stroke Research Articles

Causal association of inflammation with ischemic stroke and its subtypes: a bidirectional Mendelian randomization study.

Emerging evidence underscores a bidirectional relationship between ischemic stroke (IS) and inflammation, yet the causality of this association remains uncertain. We conducted a two-sample bidirectional Mendelian randomization (MR) study aimed at investigating the causal links between inflammation and IS. Single nucleotide polymorphism from genome-wide association studies of 112 inflammatory cytokines and IS were chosen as instrumental variables. We evaluated the causal effects of inflammatory factors on IS outcomes and examined the mediating effects of risk factors for IS. Additionally, reverse MR analysis was conducted to determine whether the occurrence of IS influenced levels of inflammatory cytokines. Causal associations were assessed using inverse variance weighting, complemented by sensitivity analyses incorporating weighted median and MR-Egger methods. We found associations between genetically predicted plasma levels of 25 inflammatory factors and IS along with its subtypes. MR supports smoking, body mass index, atrial fibrillation, coronary artery disease, heart failure, systolic blood pressure, diastolic blood pressure and type 2 diabetes as risk factors for IS. Notably, coronary artery disease and heart failure seemed to mediate the RANTES, HGF, IL-5 associations with IS. In addition, reverse MR analysis suggested a causal relationship between IS and its subtypes and 19 inflammatory factors. In summary, inflammation was suggestively causally associated with the risk of IS, and inflammatory cytokines had downstream effect on IS. Future studies should explore whether inflammatory factors found to have significant associations with IS risk could be manipulated to reduce IS risk, and the neuroinflammatory mechanisms after IS.

Comorbidities, long-term outcome and poststroke epilepsy associated with ischemic stroke - A multicenter observational study of 125 dogs.

Little is known regarding the comorbidities and prognostic factors associated with the long-term outcome of ischemic stroke in dogs. Although poststroke epilepsy is a well-recognized syndrome in people, it is unclear if this phenomenon also occurs in dogs. Document comorbidities, long-term outcome (survival and stroke recurrence), and occurrence of epileptic seizures associated with ischemic stroke. One hundred and twenty-five client-owned dogs. Multicenter observational study including dogs diagnosed with ischemic stroke between 2000 and 2021. Associations between comorbidities, stroke location and extent, poststroke epileptic seizures, and long-term outcome were investigated. Referring veterinarians and owners were contacted to obtain follow-up information. Fifty-two dogs (41.6%) had a comorbidity. The most common comorbidities were hypertension (20%) and proteinuria (8%). Eight dogs (6.4%) that did not survive to discharge had a territorial ischemic stroke. Overall median survival time for dogs with a comorbidity was 482 days (range, 1-3013) and 907 days (range, 1-3027) in dogs without comorbidities (Kaplan-Meier survival analysis P = .602). Twenty-four dogs (19.2%) had a suspected stroke recurrence and a total of 8/109 dogs (7.3%) developed poststroke epilepsy. No association was found between suspected stroke recurrence or development of poststroke epilepsy and survival (P = .812, P = .487). Despite no significant difference in survival of dogs diagnosed with ischemic stroke, with or without comorbidities, investigations for underlying causes are recommended to provide appropriate treatment. Poststroke epilepsy is uncommon.

Comparative Outcomes of Intravenous, Intranasal, and Intracerebroventricular Transplantation of Human Neural Stem Cells in Mice Model of Ischemic Stroke.

Transplantation of neural stem cells improves ischemic stroke outcomes in rodent models and is currently in the clinical test stage. However, the optimal delivery route to achieve improved efficacy remains undetermined. This study aims to evaluate three more clinically feasible delivery routes: intravenous (IV), intranasal (IN), and intracerebroventricular (ICV). We compared the therapeutic efficacies of the three routes of transplanting human neural stem cells (hNSCs) into mice with permanent middle cerebral artery obstruction (pMCAO). Behavioral tests and cresyl violet staining were used to evaluate the therapeutic efficacies of functional recovery and lesion volumes. The expression of proinflammatory cytokines and neurotrophic factors was measured by real-time PCR. The distribution and differentiation of hNSCs were determined by immunofluorescence staining. The effect on endogenous neurogenesis and astrocyte function were determined by immunofluorescence staining and western blot. hNSC transplantation using the three routes improved behavioral outcomes and reduced lesion volumes; IV transplantation of hNSCs results in earlier efficacy and improves the inflammatory microenvironment. The long-term distribution and differentiation of transplanted hNSCs in the peri-infarct areas can only be evaluated using ICV delivery. IV and ICV transplantation of hNSCs promote neurogenesis and modulate the dual function of astrocytes in the peri-infarct areas. IV and IN delivery is suitable for repeated administration of hNSCs to achieve improved prognosis. Comparatively, ICV transplantation provides long-term efficacy at lower doses and fewer administration times.

The European Registry for Patients with Mechanical Circulatory Support (EUROMACS) of the European Association for Cardio-Thoracic Surgery Fourth report: Focus on standardized outcome ratios.

This fourth report aimed to provide insights into patient characteristics, outcomes, and standardized outcome ratios of patients implanted with durable Mechanical Circulatory Support across participating centers in the European Registry for Patients with Mechanical Circulatory Support (EUROMACS) registry. All registered patients receiving durable mechanical circulatory support up to August 2024 were included. Expected number of events were predicted using penalized logistic regression. Standardized outcome ratios (Observed/Expected events) were presented in plots to assess 30-day and 1-year mortality, ischaemic stroke, and major bleeding outcomes. Expected events were estimated using penalized logistic regression using demographics and comorbidities as predictors. Centers with <90% follow-up completeness were excluded from standardized outcome ratio assessment. Analysis included 6962 implants in 6408 patients (457 patients underwent repeated implants) registered in EUROMACS from 17 countries (32 centres) (median age: 58 years, 83% males, 17% INTERMACS class 1). Thirty-day mortality, major bleeding and ischaemic stroke probabilities were 9.6, 12.6%, and 2.1%, respectively. Standardized mortality ratios showed variability between centres, ranging from 0 (95% CI : 0-0) to 1.4 (95% CI : 1.2-1.7). Higher standardized bleeding outcome ratios correlated with higher standardized ischaemic stroke ratio's (Spearman r: 0.56, P = 0.008). Most included centers perform as expected given the demographics and comorbidities of patients. A positive correlation was found between standardized bleeding and ischaemic stroke ratios, reflecting the need of continuously monitoring of adverse events by quality improvement programs.

Impact of non-alcoholic fatty liver disease and liver fibrosis on outcomes of acute ischemic stroke: A systematic review and meta-analysis

Objective: We reviewed the evidence on the impact of non-alcoholic fatty liver disease (NAFLD) and liver fibrosis on mortality, functional dependence, and recurrence after acute ischemic stroke (AIS). Methods: This PROSPERO registered review searched PubMed, Embase, CENTRAL, and Web of Science databases from inception of databases to 30th July 2023 for studies comparing outcomes of AIS based on the presence of NAFLD and liver fibrosis. Adjusted data on mortality, functional dependence and risk of recurrent AIS was pooled to obtain odds ratio (OR) with 95% confidence intervals (CI) in a random-effects model Results: Ten studies were included. Descriptive analysis showed conflicting effects of NAFLD on AIS outcomes with some studies showing better functional outcomes with the presence of NAFLD. Meta-analysis showed that the presence of liver fibrosis was associated with a significantly increased risk of mortality (OR: 2.22 95% CI: 1.02–4.86 I2=92%) and functional dependence (OR: 1.89 95% CI: 1.27–2.82 I2=53%) as compared to no fibrosis. Meta-analysis found that liver fibrosis did not increase the risk of recurrent AIS (OR: 1.32 95% CI: 0.74–2.37 I2=74%). Conclusion: Scant evidence exists for the effect of NAFLD and liver fibrosis on AIS outcomes. A paradoxical effect of NAFLD on functional outcomes has been noted which needs confirmation by future studies. Liver fibrosis was found to increase the risk of mortality and functional dependence in AIS. doi: https://doi.org/10.12669/pjms.41.2.10729 How to cite this: Yang L, Han J, Qin C, Song F. Impact of non-alcoholic fatty liver disease and liver fibrosis on outcomes of acute ischemic stroke: A systematic review and meta-analysis. Pak J Med Sci. 2025;41(2):630-636. doi: https://doi.org/10.12669/pjms.41.2.10729 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Outcome of acute ischemic stroke with absent opacification of the cervical internal carotid artery at CT-angiography after endovascular treatment.

Purpose: Occlusion of the distal internal carotid artery can simulate a proximal occlusion of its cervical tract on CT angiography in patients with acute ischemic stroke, that is, pseudo-occlusion. As true and false carotid occlusions can present similarly on non-invasive imaging in patients undergoing endovascular treatment for stroke, our study aimed to evaluate clinical and technical differences of these conditions and the possible consequences of a misdiagnosis. Methods: We retrospectively reviewed consecutive patients who underwent mechanical thrombectomy for acute ischemic stroke at a single center between July 2015 and May 2022 and included patients with absent opacification of the cervical carotid artery on CT-angiography. Digital subtraction angiography (DSA) imaging and procedural data were evaluated to define the actual localization of the occlusion. We compared imaging and clinical data between patients with true and false carotid occlusion, including collateral circulation at CTA, revascularization grade, and clinical outcome at 3months. Results: A total of 116 patients were included, 63 (54%) of whom had true occlusion of cervical internal carotid artery. Compared to the pseudo-occlusion group, collateral circulation at CTA was moderate to good in 75% of cases (vs 32%; p < 0.0001) and the mean ASPECT score at 24h was 7 versus 2 (p < 0.0001). Modified Rankin scale 0-2 at 90days was more frequent in patients with true occlusion than those with pseudo-occlusion (48 vs 11%; p = 0.0002). Conclusion: Pseudo-occlusion of the cervical internal carotid artery in patients with acute ischemic stroke appears to be associated with worst prognosis and poorer collateral circulation in comparison with tandem occlusion.

Prediction of tissue and clinical thrombectomy outcome in acute ischaemic stroke using deep learning.

The advent of endovascular thrombectomy has significantly improved outcomes for stroke patients with intracranial large vessel occlusion, yet individual benefits can vary widely. As demand for thrombectomy rises and geographic disparities in stroke care access persist, there is a growing need for predictive models that quantify individual benefits. However, current imaging methods for estimating outcomes may not fully capture the dynamic nature of cerebral ischemia and lack a patient-specific assessment of thrombectomy benefits. Our study introduces a deep learning approach to predict individual responses to thrombectomy in acute ischemic stroke patients. The proposed models provide predictions for both tissue and clinical outcomes under two scenarios: one assuming successful reperfusion and another assuming unsuccessful reperfusion. The resulting simulations of penumbral salvage and difference in NIHSS at discharge quantify the potential individual benefits of the intervention. Our models were developed on an extensive dataset from routine stroke care, which included 405 ischemic stroke patients who underwent thrombectomy. We used acute data for training (n = 304), including multimodal CT imaging and clinical characteristics, along with post hoc markers like thrombectomy success, final infarct localization, and NIHSS at discharge. We benchmarked our tissue outcome predictions under the observed reperfusion scenario against a thresholding-based clinical method and a generalised linear model. Our deep-learning model showed significant superiority, with a mean Dice score of 0.48 on internal (n = 50) and 0.52 on external (n = 51) test data, versus 0.26/0.36 and 0.34/0.35 for the baselines, respectively. The NIHSS sum score prediction achieved median absolute errors of 1.5 NIHSS points on the internal test dataset and 3.0 NIHSS points on the external test dataset, outperforming other machine learning models. By predicting the patient-specific response to thrombectomy for both tissue and clinical outcomes, our approach offers an innovative biomarker that captures the dynamics of cerebral ischemia. We believe this method holds significant potential to enhance personalised therapeutic strategies and to facilitate efficient resource allocation in acute stroke care.

Association of endovascular thrombectomy volume and outcomes in acute ischemic stroke: A National Inpatient Sample Study.

Previous studies suggest a positive relationship between higher hospital endovascular thrombectomy (EVT) volume and improved outcomes. We investigated this association using the National Inpatient Sample (NIS) database from 2016 to 2020. A cross-sectional analysis of the NIS examined the relationship between hospital EVT volume and outcomes. Data on clinical and demographic variables were collected. Outcomes included favorable functional outcome (discharge home without assistance), inpatient mortality, and intracerebral hemorrhage (ICH). Hospitals in the top quintile of annual EVT volume were classified as high-volume centers. We conducted univariate, multivariate, nearest neighbor matched analysis, and an exploratory analysis to identify annual EVT volume cutoffs. Among 114,640 patients with EVT, 24,415 (21.3%) were treated at high-volume centers. High-volume centers had higher rates of favorable functional outcomes in univariate (odds ratio (OR) 1.20, p < 0.001), multivariate (adjusted OR (aOR) 1.19, p = 0.003), and matched analysis (OR 1.14, p = 0.028). Before matching, inpatient mortality was lower in high-volume centers (OR 0.83, p < 0.001), but this difference was not significant in univariate and matched analyses. No differences in ICH were observed. Functional benefit was noted at ≥ 50 EVTs annually, with centers performing ≥ 175 EVTs showing significantly higher benefits (aOR 1.42, p = 0.002). Increased hospital EVT volume is associated with modestly improved functional outcomes in patients with acute ischemic stroke. Functional improvements are evident at ≥ 50 EVTs annually and increase with higher case volumes, without associated increases in inpatient mortality or ICH.

Association Between Time to Treatment and Outcomes of Endovascular Therapy vs Medical Management in Patients With Large Ischemic Stroke.

Randomized trials have proven the benefit of endovascular therapy (EVT) for acute large ischemic stroke. This study was to characterize the effect of time to treatment on benefit of EVT vs medical management (MM) among patients with large ischemic stroke. This was a post hoc analysis of the Endovascular Therapy in Acute Anterior Circulation Large Vessel Occlusive Patients with a Large Infarct Core randomized trial. Patients who had an Alberta Stroke Program Early Computed Tomography Score of 3-5 or an ischemic core volume of 70-100 mL within 24 hours of symptom onset were treated with EVT plus MM or MM. Onset-to-expected arterial puncture time (OPT) was analyzed as a categorical variable (<6, 6-<12, and 12-24 hours) using binary logistic regression and as a continuous variable using a multivariable fractional polynomial interaction. The primary efficacy outcome was favorable outcomes (modified Rankin Scale scores 0-3) at 90 days. Safety outcomes included any intracranial hemorrhage (ICH), symptomatic ICH, and mortality. Among 451 patients (median age 68 years; 61.4% were men; median OPT 487 minutes [interquartile range 328-802]), 226 patients received EVT and 225 patients received MM. The EVT group showed higher rates of favorable outcomes than the MM group within OPT of 6 hours (44.4% vs 29.9%, adjusted odds ratio [aOR] 2.78, 95% CI 1.22-6.32) and 6-12 hours (45.7% vs 29.6%, aOR 2.39 [95% CI 1.21-4.71]), but not in OPT beyond 12 hours (51.6% vs 41.4%, aOR 2.05 [95% CI 0.88-4.77]). The benefit became nonsignificant after OPT of 13 hours and 22 minutes. In 3 OPT intervals, the rates of symptomatic ICH and mortality were similar between EVT and MM although the rate of any ICH increased. However, no interaction effect was found (all p interactions >0.10). These findings strengthen the benefit of EVT initiated within 13 hours and 22 minutes after symptom onset compared with MM alone in patients with large ischemic stroke, but EVT should not be withheld for patients presenting beyond 13 hours and 22 minutes. Pooled analysis of larger sample sizes is needed. ClinicalTrials.gov; NCT04551664. This study provides Class II evidence that EVT is associated with improved functional outcomes for acute large ischemic stroke within 24 hours after last known well, with no interaction by time.

Mechanism of Ligusticum wallichii-Borneol in the Treatment of Cerebral Ischemic Stroke in Rats Based On Network Pharmacology, Molecular Docking, and Experimental Verification.

The pharmacodynamics, molecular biology, network pharmacology, and molecular docking mechanisms of the Ligusticum wallichii and borneol medication pair (CXBP) were investigated for ischemic stroke treatment. Effective chemical components and targets of CXBP were identified using TCMSP, ETCM, and SymMap databases, whereas ischemic stroke targets were sourced from OMIM, GeneCards, TTD, PubMed, Web of Science, CNKI, Wanfang Data, and VIP databases. Protein-protein interaction (PPI) networks were generated using the STRING database, and GO and KEGG enrichment analyses were conducted using Metascape. A "disease-pathway-target-component-drug" network was created in Cytoscape, and molecular docking was confirmed with PyMOL and AutoDock tools. Rat models of MCAO were established to evaluate neurological scores, triphenyltetrazolium chloride (TTC) staining, and Nissl staining. Key components were validated through enzyme-linked immunosorbent assay (ELISA), real-time polymerase chain reaction (PCR), and immunohistochemistry. Thirty-three active ingredients and 419 potential targets for CXBP, with key compounds including Z-6,8',7,3'-diligustilide, cedrene, (+)-alpha-funebrene, POL, dipterocarpol, oleanolic acid, 1-acetyl-beta-carboline, and erythrodiol. Critical targets included ESR1, PRKCA, and PTPN6. KEGG pathway analysis revealed 179 signaling pathways, primarily neuroactive ligand-receptor interactions, whereas GO enrichment analysis identified 2911 biological processes, 398 molecular activities, and 203 cellular components. The neurological function scores and TTC staining of the infarcted brain regions were significantly improved following CXBP intervention compared to the MCAO group. These findings were supported by Nissl staining, which demonstrated better preserved cellular morphology and a significantly higher number of Nissl vesicles in the CXBP group. ELISA analysis revealed substantial modulation in gene expression: levels of PRKCA, PTPN6, ESR1, and TNF-α changed significantly, whereas IL-1β, IL-6, and TNF-α were notably downregulated compared to the MCAO group. PCR results corroborated these findings, showing a significant decrease in PRKCA expression and marked downregulation of IL-1β, IL-6, and TNF-α, whereas ESR1 and PTPN6 levels increased significantly. Immunohistochemical analysis further confirmed these results, with the CXBP and nimodipine groups exhibiting higher ESR1 and PTPN6 expression and lower PRKCA expression compared to the MCAO group. To improve cerebral ischemia and reperfusion injury, CXBP improves ischemic stroke outcomes through key active ingredients (e.g., Z-6,8',7,3'-diligustilide, cedrene, and oleanolic acid) and targets ESR1, PRKCA, and PTPN6, modulating multiple signaling pathways to alleviate cerebral ischemia-reperfusion injury.

Relationship between triglyceride-glucose index and intravenous thrombolysis outcomes for acute ischemic stroke

Aims: The aim of this study was to investigate the effect of triglyceride glucose index, a marker of insulin resistance, on early neurological deterioration (END), development of intracerebral hemorrhage and hemorrhagic transformation and mortality in patients receiving intravenous thrombolytic therapy for acute ischemic stroke. Methods: This retrospective study included 71 patients with acute ischemic stroke who received intravenous tissue plasminogen activator. Demographic data, clinical and radiological findings, fasting glucose and lipid profile, END, hemorrhage development and mortality rates were analyzed. We also calculated the triglyceride glucose (TyG) index and examined its correlation with early neurological deterioration, hemorrhage development and mortality. Results: The median age was 74 years (41-88), with a female predominance of 54.9%. The incidence of intracerebral hemorrhage was 9.6%, while END occurred in 39.6% of cases, and the 30-day mortality rate was 28.2%. The mean TyG index was 7.8 (2.8-27.6). The receiver operating characteristic curve analysis indicated that the TyG index predicted mortality with an area under the curve of 84.4%, a sensitivity of 85%, and a specificity of 82.35% in patients with a TyG index above 10.01 (p

Association between HALP (hemoglobin, albumin, lymphocyte, and platelet) score and poor outcomes in acute ischemic stroke patients with type 2 diabetes mellitus: a study from the Third China National Stroke Registry.

The combined index (HALP) of hemoglobin, albumin, lymphocytes, and platelets is considered a novel scoring system that reflects systemic inflammation and nutritional status. This study aimed to investigate the relationship between HALP scores and poor outcomes in acute ischemic stroke (AIS) patients with type 2 diabetes mellitus (DM). Patients with AIS and type 2 DM were screened from the Third China National Stroke Registry (CNSR-III) and divided into quartiles based on their HALP scores at admission. Clinical outcomes were adverse functional outcomes (modified Rankin scale [mRS] score of 3-6 or 2-6) and all-cause mortality at 3 months and 1 year. The association of HALP with the risk of poor functional outcome and all-cause mortality were analyzed by multivariable logistic regression and Cox proportional hazards regression. A total of 3,603 patients were included in this study. After adjusting for confounders, it was found that patients in the highest HALP score quartile had lower mRS scores of 2-6 (odds ratio [OR], 0.64; 95% confidence interval [CI], 0.51-0.80) and 3-6 (OR, 0.53; 95% CI, 0.51-0.82) at the 3-month follow-up. At the 1-year follow-up, a significant correlation was observed between HALP scores and mRS scores of 2-6 (OR, 0.65; 95%CI, 0.57-0.81) and 3-6 (OR, 0.64; 95%CI, 0.47-0.86). Additionally, the highest HALP score quartile was associated with a reduced risk of all-cause mortality at the 3-month follow-up (hazard ratio [HR], 0.35; 95%CI, 0.13-0.93). Similar results were observed at the 1-year follow-up (HR, 0.34; 95%CI, 0.18-0.63). At 3 months of AIS patients with type 2 diabetes and 1-year follow-up, lower HALP scores were associated with poorer functional outcomes and all-cause mortality.

Overexpressed CD73 attenuates GSDMD-mediated astrocyte pyroptosis induced by cerebral ischemia-reperfusion injury through the A2B/NF-κB pathway.

Ischemic stroke, resulting from the blockage or narrowing of cerebral vessels, causes brain tissue damage due to ischemia and hypoxia. Although reperfusion therapy is essential to restore blood flow, it may also result in reperfusion injury, causing secondary damage through mechanisms like oxidative stress, inflammation, and excitotoxicity. These effects significantly impact astrocytes, neurons, and endothelial cells, aggravating brain injury and disrupting the blood-brain barrier. CD73, an ectoenzyme that regulates adenosine production through ATP hydrolysis, plays a critical role in purinergic signaling and neuroprotection. During ischemic stroke, CD73 expression is dynamically regulated in response to ischemia and inflammation. It catalyzes the conversion of AMP to adenosine, which activates adenosine receptors to exert neuroprotective effects. Targeting the CD73-adenosine pathway presents a potential therapeutic strategy for mitigating ischemic stroke damage. Pyroptosis, a highly inflammatory form of programmed cell death mediated by inflammasomes like NLRP3 and caspases, plays a significant role in cerebral ischemia-reperfusion injury. Astrocytes, the most abundant CNS cells, contribute to both neuroprotection and injury, with pyroptosis exacerbating inflammation and brain damage. Regulating astrocyte pyroptosis is a promising therapeutic target. Our study investigates CD73's role in regulating astrocyte pyroptosis during ischemia-reperfusion injury. Using CD73 knockout mice and overexpression models, along with in vitro oxygen-glucose deprivation/reperfusion experiments, we found that CD73 overexpression reduces GSDMD-mediated astrocyte pyroptosis via the A2B/NF-κB pathway. These findings offer a novel approach to reducing neuroinflammation, protecting astrocytes, and improving outcomes in ischemic stroke.

Therapeutic Potential of Mesenchymal Stem Cell-Derived Extracellular Vesicles in Ischemic Stroke: A Meta-Analysis of Preclinical Studies.

Ischemic stroke (IS) remains a significant global health burden, necessitating the development of novel therapeutic strategies. This study aims to systematically evaluate the therapeutic effects of mesenchymal stem cell-derived exosomes (MSC-Exos) on IS outcomes in rodent models. A comprehensive literature search was conducted across multiple databases to identify studies investigating the effects of MSC-Exos on rodent models of IS. Following rigorous inclusion and exclusion criteria, 73 high-quality studies were selected for meta-analysis. Primary outcomes included reductions in infarct volume/ratio and improvements in functional recovery scores. Data extraction and analysis were performed using RevMan 5.3 software. Pooled data indicated that MSC-Exos administration significantly reduced infarct size and improved functional recovery scores in rodent models of IS. Treatment within 24hours and beyond 24hours of stroke induction both demonstrated substantial reductions in infarct volume/ratio compared to controls. Furthermore, MSC-Exos-treated groups exhibited marked improvements in functional recovery, as assessed by various neurobehavioral tests. The meta-analysis showed no significant publication bias, and heterogeneity levels were acceptable. MSC-Exos reveal significant therapeutic potential for IS, with evidence supporting their efficacy in reducing infarct size and enhancing functional recovery in preclinical rodent models. These findings pave the way for further research and potential clinical translation.

The Association of SUR1 Polymorphisms with Acute Infarct Size: The MRI-GENIE Study.

Background: The sulfonylurea receptor 1 (SUR1) is a known mediator of cerebral edema in large ischemic strokes, however, genetically induced response variability has yet to be evaluated. SUR1, encoded by the ABCC8 gene, is an ion channel regulator in ischemia-induced cerebral edema. Previous studies in severe traumatic brain injury demonstrated four tag single nucleotide polymorphisms (SNPs) of the ABCC8 gene to be associated with cerebral edema and functional outcome. We hypothesized that these four SNPs would also be associated with acute infarct size and functional outcome in non-lacunar ischemic stroke. Methods: Using 2,205 MRI–GENetics Interface Exploration (MRI-GENIE) study subjects with acute non-lacunar ischemic strokes, we evaluated the association between the 4 ABCC8 tag-SNPs and stroke infarct size (as measured in a standardized fashion from MRIs using diffusion-weighted imaging), adjusting for age, sex and population stratification. Modified Rankin scale (mRS) outcome was available at 3-months for a subset of 798 strokes in MRI-GENIE and was evaluated as a dichotomous variable (0-2 vs 3-6), adjusting for age, sex, stroke severity (baseline NIH Stroke Scale (NIHSS) score), and population stratification. Results: The candidate SNPs, rs7105832, rs2237982, rs11024286, rs4148622, were not statistically associated with DWI (beta= -0.065, -0.057, 0.037, 0.018; p=0.053, 0.078, 0.28, 0.61) or dichotomous mRS outcome (OR=0.80, 0.86, 1.14, 0.90; p=0.117, 0.289, 0.353, 0.502). Conclusion: rs7105832, rs2237982, rs11024286, rs4148622 polymorphisms of the ABCC8 gene did not demonstrate a significant effect on acute ischemic infarct size or 3-month functional outcome. Nonetheless, further studies with delayed imaging and more sensitive outcome measures remain warranted.

Effect of prior use of statins on endovascular thrombectomy outcomes in acute ischemic stroke.

Acute large vessel occlusions (LVOs) account for up to one-third of acute ischemic strokes (AIS) and are associated with high mortality and severe functional deficits. Animal model research suggests that statins may have a protective effect on vessel wall injury during endovascular thrombectomy (EVT). We conducted a retrospective observational study to assess the impact of statin use on clinical outcomes post-EVT in AIS patients with LVOs. Using the Global Collaborative Network consisting of about 143 million patients in TriNetX database, we identified adult AIS patients who underwent EVT between 2018 and 2023. Patients were categorized based on any statin use (atorvastatin, simvastatin, rosuvastatin, pravastatin, lovastatin, or pitavastatin) in the 3 months before AIS admission. The primary outcome was all-cause mortality at one-week post-EVT. Secondary outcomes included intracerebral hemorrhage (ICH), subarachnoid hemorrhage (SAH), decompressive hemicraniectomy procedure (DHC), and aspiration pneumonia at one-week post-EVT. Propensity score matching balanced relevant medical history, stroke severity, medications, and demographics. Cox proportional hazard regression analysis compared outcomes between statin and non-statin cohorts. We identified 17,774 patients who received EVT for LVO ischemic stroke. A total of 10,678 patients were on statins during 3 months prior to EVT and 7096 patients were not on statins. After 1:1 propensity matching, 2148 patients were included in each group. AIS patients treated with EVT and on statins had lower risk of all-cause mortality [7 % vs. 17 %; HR 0.43, 95 % CI 0.35-0.51], ICH [10 % vs. 15 %; HR 0.64, 95 % CI 0.51-0.74], SAH [3 % vs. 6 %; HR 0.48, 95 % CI 0.35-0.64], and aspiration pneumonia [4 % vs 8 %; HR 0.53, 95 % CI 0.41-0.70] compared to AIS patients treated with EVT but not on statins. Rates of DHC were similar between groups [2 % vs 2 %; HR 0.81; 95 % CI (0.52,1.25)]. Statin use within 3 months prior to AIS was associated with better survival and lesser intracranial bleeding risks and complications following EVT. Future studies may help examine how the duration or dosages of statins or LDL levels on admission affect outcomes in LVO strokes treated with EVT.

Effect of Mean Platelet Volume on Outcome of Stroke Infark in Elderly Patient

Abstract Introduction: Hyperreactivity and activation of platelet play a role in the occurrence and severity of ischemic stroke in geriatric patients. Mean Platelet Volume (MPV) describes levels of stimulation as well as platelet production rates that may affect the incidence of ischemic stroke and its clinical outcome. Aim : To determine the effect of MPV on the outcome of stroke infarction in geriatric patients. Methods. This was a cohort study. MPV measured at the beginning of hospital admission. Statistical analysis carried out by Receiver of Curve (ROC) test to determine the MPV cut off point and Chi-square to determine the relationship between MPV and infarction of stroke patient using SPSS software version 22. Result. There were 52 stroke patients with mean age 68.25+6.06 years old. Clinical outcomes of the patient deteriorated in 38 (73.08%) patients. The AUC value of MPV was73.3% (p=0.011) with MPV cut off point 10.85fl. Deterioration occurred in 10 (43.38%) patient with MPV levels &gt;10.85fl. The Chi-square test result was (p&lt;0.001) implying a significant difference between the groups (RR 3.125 CI 95% 1.134-8.761). Weconcluded that ischemic stroke patients with MPV levels &gt;10.85fl at hospital admission has 3 times chance of deterioration. Conclusion. MPV can be used as prognostic factor for clinical outcome of acute ischemic stroke in geriatric patients. Keyword: Mean Platelet Volume, Ischemic Stroke, Geriatric

Predictive Value of NT-proBNP for Functional Outcome of Ischemic Stroke Without Cardiac Disease: A Prospective, Observational Study

Predictive Value of NT-proBNP for Functional Outcome of Ischemic Stroke Without Cardiac Disease: A Prospective, Observational Study

Benzydamine attenuates microglia-mediated neuroinflammation and ischemic brain injury by targeting cathepsin s.

Microglia, the primary immune cells of the central nervous system, play a crucial role in the neuroinflammatory processes following ischemic stroke. Targeting neuroinflammation is a promising strategy to enhance the outcomes of ischemic stroke. Benzydamine (BA), a well-known non-steroidal anti-inflammatory drug, has demonstrated potential in inhibiting pro-inflammatory cytokines across various disease models. However, the potential role of BA in microglial activation and post-stroke neuroinflammation remains unclear. Our study reveals that BA effectively suppresses the lipopolysaccharide (LPS)-stimulated pro-inflammatory responses of primary microglia, with high-dose BA (10μM) suppressing LPS-induced inflammatory markers by up to 59.1% in the mRNA levels of IL-1β. Furthermore, BA mitigated ischemic brain injury in experimental stroke mice. BA treatment also significantly attenuated neuroinflammatory responses and attenuates ischemic brain injury in experimental stroke mice. Further investigation revealed that BA reduces the release of the LPS-stimulated pro-inflammatory factors and activation of primary microglia by directly binding to and inhibiting the activity of cathepsin S (CTSS). In conclusion, our study identifies BA as a promising CTSS inhibitor with potential to suppress neuroinflammation following ischemic stroke. Our findings provide a theoretical basis for developing new neuroprotective strategies.

Intravenous thrombolysis and mechanical thrombectomy in acute stroke patients on direct oral anticoagulants

Intravenous thrombolysis and mechanical thrombectomy reduce morbidity and improve functional outcome in ischemic stroke. However, acute recanalization therapies may increase the risk of symptomatic intracranial hemorrhage due to its effects on the brain tissue. An increasing proportion of patients with ischemic stroke are using direct oral anticoagulants (DOACs). While current international guidelines recommend against intravenous thrombolysis in patients with intake of DOACs within the last 48 h, they also highlight lack of evidence in the area. Based on these guidelines, a significant proportion of patients are consequently disqualified from intravenous thrombolysis. Measuring anticoagulant activity before intravenous thrombolysis has been suggested as a way to select patients with low risk of symptomatic intracranial hemorrhage, but uncertainty exists about feasibility, validity, availability and costs. Reversal agents have demonstrated potential in facilitating safer intravenous thrombolysis administration, though their efficacy is not established in randomized controlled trials, and logistical and cost-related barriers limit their widespread use. During the last couple of years several large cohort studies reported no significant increase in symptomatic intracranial hemorrhage among selected patients on DOACs receiving intravenous thrombolysis compared to those not on anticoagulants, even without the use of DOAC plasma levels or reversal agents. Mechanical thrombectomy appears to be generally safe in patients with recent DOAC intake. The aim of this review is to discuss the uncertainty around the safety and efficacy of intravenous thrombolysis and thrombectomy in patients with a recent intake of DOAC, summarize existing knowledge, and outline potential approaches.