Search Results for: Sviluppo di un test meno invasivo per la malattia infiammatoria intestinale

Stroke, Volume 56, Issue Suppl_1, Page ATP311-ATP311, February 1, 2025. Introduction:Immune Checkpoint Inhibitors (ICIs) used for treatment of malignancies might promote atherosclerosis and increase the risk of ischemic stroke (IS). We aimed to compare IS characteristics of patients with non-small cell lung cancer (NSCLC) who received ICIs compared to those who did not. We hypothesized that IS associated with atherosclerosis will be more common among those treated with ICIs than other treatments.Methods:A retrospective single center study of patients,18 or older, with NSCLC presenting between 2013 and 2023, treated with either ICIs, chemotherapy, or a combination and had an IS any time following treatment. Patients without vessel imaging were excluded. We collected demographics and stroke characteristics. Two sample Mann-Whitney U and chi-square test were used to compare demographics and stroke etiologies among patients who received chemotherapy and those who received ICIs with or without chemotherapy.Results:A total of 58 patients were identified, 22 received chemotherapy only and 36 received ICIs. The mean age was 68.8, with 50% male (29/58). ICI treated groups had significantly more stage IV diagnoses (chemotherapy only 3.6%, ICI 67%, p=0.04). There was no difference in median time from treatment to stroke onset in days between groups; chemotherapy 90.5 (range 27-386) vs. ICI 337.5 (range 95-665), p= 0.39. The stroke etiology in those treated with chemotherapy alone were as follows: Large artery atherosclerosis (3), cardioembolic (8), small vessel disease (5), ESUS (5), other (1). For those treated with either ICI alone or ICI and chemotherapy: Large artery atherosclerosis (5), cardioembolic (6), small vessel disease (2), ESUS (23), other (0). Stroke etiology consistent with embolic stroke with unknown source (ESUS) was more common in the ICI group (chemotherapy only 2.3%, ICI 64%, p=0.02).Conclusions:Contrary to prior research suggesting atherogenesis with ICI, the most common stroke etiology in the ICI group was ESUS.

Stroke, Volume 56, Issue Suppl_1, Page ATP312-ATP312, February 1, 2025. Background/Objectives:Perioperative stroke is a significant cause of morbidity and mortality in patients undergoing cardiac, vascular, and neurosurgical procedures. We assessed the rate, characteristics, risk factors and survival outcomes of perioperative stroke following surgical resection of glioma.Design:This is a retrospective chart review of a single quaternary care center of patients with glioma between 2005-2021 who underwent resection. Stroke within 30 days of surgical resection was identified based on the radiology read of MRI brain for ischemic stroke and CT brain for hemorrhagic stroke that was obtained as part of clinical care. This was then confirmed retrospectively by a neurologist who reviewed imaging and medical records, excluding expected post-operative changes. Descriptive analysis and logistic regression were conducted. Overall survival was estimated with Kaplan-Meier methods from the date of surgery to death and compared with the log rank test.Results:Out of 738 patients who underwent surgical resection of their glioma and underwent brain MRI or CT head, 20 (2.71%) had radiographic evidence of strokes, with the mean (SD) time from surgery to stroke 5.4 (16.2) days. Of these, 13 (65%) had ischemic strokes, 7 (35%) had hemorrhagic strokes. Out of all perioperative strokes, 9 (45%) were symptomatic (total incidence of 1.2%), and 11 (55%) were asymptomatic. Patients who had a stroke were older [mean (SD); 60.4 (13.7) vs. 52.8 (15.0) years; p=0.026], had a higher rate of atrial fibrillation (p= 0.002), and had comorbid hyperlipidemia (p=0.039) and hypertension (p=0.047). Descriptive analysis of this cohort is summarized in Table 1. Older age, carrying a diagnosis of atrial fibrillation, and having hyperlipidemia were associated with higher odds of having a perioperative stroke (Table 2). In an attempt to generate a multivariate logistic model, stepwise selection yielded no significant results likely due to the low number of strokes in this cohort. The median survival for patients with stroke was 24.6 months (95% CI:21.8-32.1), which was lower than for patients who did not suffer a stroke (29.3 months, 95% CI: 25.6-32.9) (p=0.052).Conclusion:Older age, atrial fibrillation, hyperlipidemia, and hypertension were associated with perioperative stroke risk after glioma resection. Future studies should evaluate underlying mechanisms and stroke etiologies to better identify high risk patients.

Stroke, Volume 56, Issue Suppl_1, Page AWP181-AWP181, February 1, 2025. Background:Timely intervention is crucial for patients with acute ischemic stroke. The RapidAI imaging system (RAPID) was implemented to enhance the speed and efficiency of care delivery. We evaluated the impact of RAPID on various metrics in the patient care pathway.Methods:In this retrospective observational study, we analyzed consecutive patients who presented to our hospital ER with acute ischemic stroke and who were treated with Intravenous Thrombolysis (IVT) or mechanical thrombectomy between December 20, 2014, and April 20, 2024. Patients were divided into pre-RAPID (n =186) and post-RAPID (n =264) groups based on the implementation date of the RAPID system (September 1, 2019). We compared Door to Non-contrast CT (NCCT), Door to CT Angiography (CTA) / Perfusion Imaging, Door to IVT, and Door to Puncture / first pass for thrombectomy, between the two groups using Fisher’s exact test.Results:For Door to CT, no significant difference was observed between pre-RAPID and post-RAPID groups; 74% of patients in the post-RAPID group and 71% in the pre-RAPID group received NCCT within 45 minutes (p= 0.44). Significant improvements were observed in Door to CTA/Perfusion times; 90% of patients received vessel or perfusion imaging within 150 minutes post-RAPID compared to 70% pre-RAPID (p= 0.01), and 87% received imaging within 120 minutes post-RAPID compared to 70% pre-RAPID (p= 0.031). For Door to IVT, 96% of patients received treatment within 120 minutes post-RAPID compared to 82% pre-RAPID (p= 0.015). For thrombectomy, there was a trend toward faster door to puncture post-RAPID; 70% of patients were treated within 150 minutes post-RAPID compared to 62% pre-RAPID (p= 0.36), and 90% were treated within 210 minutes post-RAPID compared to 81% pre-RAPID (p= 0.12). Similarly, a trend toward faster Door to First Pass times was observed post-RAPID, with 88% treated within 240 minutes compared to 80% pre-RAPID (p= 0.20).Conclusions:RapidAI Implementation was associated with significant improvements in key workflow metrics, notably in Door to Vessel/Perfusion Imaging and Door to IVT. These findings suggest that RAPID enhances the efficiency of patient care delivery in acute ischemic stroke. Further studies with larger sample sizes are warranted.

Stroke, Volume 56, Issue Suppl_1, Page ATMP12-ATMP12, February 1, 2025. Background:Atherosclerotic carotid artery disease is associated with a high risk of major adverse cardiac events (MACE) even with optimal risk factor management and surgical interventions such as carotid endarterectomy (CEA). Aortic stenosis (AS) is an age-related valve disease that is associated with a high rate of MACE. An artificial intelligence-based AS estimation algorithm (AI-AS) can identify AS with high accuracy using electrocardiogram. This study evaluates the prognostic value of AI-AS in patients with carotid artery disease undergoing CEA.Methods:We included patients with carotid artery disease undergoing CEA at Mayo Clinic from 2002-2023 if they had >30 days of follow-up and an electrocardiogram within one year before CEA. The electrocardiogram closest to the CEA date was used to calculate AI-AS (AS probability ranging from 0-1). MACE was defined as the composite of cardiac events, ischemic cerebrovascular accidents, and all-cause mortality during follow-up after CEA. A receiver operating characteristic curve and the Youden index were used to identify the optimal AI-AS cut-off value for predicting MACE. Kaplan Meier plot was used to depict MACE-free survival. Regression models were used to evaluate the predictive value of AI-AS for future MACE adjusting for clinical covariates.Results:A total of 665 patients with a median age of 72 [IQR:66, 78] years and 438 (65.9%) males were included. Over a median follow-up time of 7.1 [IQR:2.7, 11.5] years, MACE occurred in 419 (63%) of the patients, including 187 (44.6%) mortality, 161 (38.4%) cardiac events, and 71 (16.9%) cerebrovascular accidents. Median AI-AS was 0.32 [IQR:0.09, 0.55] in the total cohort, 0.34 [IQR:0.12, 0.56] in patients with MACE, and 0.30 [IQR:0.07, 0.53] in patients without MACE (P=0.038). AI-AS was a significant predictor of MACE (HR:2.38, 95%CI:1.64-3.46, P

Stroke, Volume 56, Issue Suppl_1, Page A82-A82, February 1, 2025. Background:Spontaneous intracerebral hemorrhage (sICH) is a neurological condition characterized by the rupture of blood vessels within the brain, resulting in the formation of a hematoma and subsequent brain injury. Tobacco use is a major modifiable risk factor for sICH and is associated with worsened outcomes following the occurrence of sICH. Tobacco use is also correlated with worsened outcomes following sICH. Previously, we observed that prior chronic exposure to nicotine results in increased hematoma volume following collagenase-induced sICH when compared to saline-exposed animals. This study aims to evaluate the effect of prior chronic nicotine exposure on long-term outcomes post-sICH.Hypothesis:Prior chronic nicotine exposure will result in more significant brain damage following an autologous blood injection-induced sICH.Methods:Young male and female (estrous matched) rats were randomly assigned to a saline (control) or nicotine-exposed group. Rats received nicotine or saline via. osmotic pumps for 2-3 weeks. The pump was removed before the induction of sICH by the stereotaxic injection of autologous blood into the striatum. The autologous blood injection-induced sICH model was used to obtain equal hematoma volume in all experimental groups. Rats then underwent perfusion fixation, and brains were harvested for histopathological analysis. Paraffin-embedded brain blocks were cut into 10 µm coronal sections between bregma -2.0 to +2.0, stained with hematoxylin and eosin, scanned with a high-resolution scanner, and analyzed using ImageJ to measure lesion area. Student’s t-test was used to determine significant differences in mean lesion volume between treatment groups. Two-way ANOVA was used to assess the interaction effect between sex and lesion volume.Results:For the male group, the brain lesion volume in nicotine-exposed rats was significantly (p

Stroke, Volume 56, Issue Suppl_1, Page AWMP113-AWMP113, February 1, 2025. Introduction:Post-stroke brain stimulation is a promising neurorestorative approach, yet the molecular mechanisms driving recovery remain unclear. Our previous work demonstrated that post-stroke optogenetic stimulations of the ipsilesional primary motor cortex (iM1) promotes functional recovery. To understand the mechanisms driving post-stroke recovery, we investigated the transcriptome of iM1 in non-stimulated and stimulated mice using RNA sequencing.Methods:C57Bl6 male mice underwent stereotaxic surgery to express Channelrhodopsin in iM1 excitatory neurons, with optical fiber implanted in the same location. After 5-6 weeks, mice underwent transient middle cerebral artery occlusion (30 minutes). Stimulated mice received optogenetic stimulations from post-stroke days (PD) 5–14. Rotating beam test was performed at pre-stroke baseline, PD4, 7 and 14. iM1 from stimulated, non-stimulated stroke mice at PD 7&15, and sham mice were processed for RNA sequencing (n=4-5/group). Expression of cholesterol enzymes such as HMGCS1 was examined using quantitative PCR and immunohistochemistry. Cholesterol levels were visualized using filipin or BODIPY.Results:iM1 stimulations enhanced recovery at PD14, with longer distance traveled and faster speed on the rotating beam test (p

Stroke, Volume 56, Issue Suppl_1, Page ATMP10-ATMP10, February 1, 2025. Introduction:An optimal strategy for the treatment of intracranial atherosclerotic disease (ICAD) has remained unclear, despite medical therapy (antiplatelet therapy and LDL control management) or endovascular therapy (angioplasty or stenting). Recently, cilostazol plus other antiplatelet agents combined therapy (CT) has been reported to reduce recurrent stroke, and eicosapentaenoic acid (EPA) has been reported to reduce the risk of cardiovascular events and plaque progression. Therefore, our hypothesis is that the addition of CT and EPA therapy may reduce stroke recurrence and further regression of stenosis.Methods:Patients with symptomatic and asymptomatic intracranial artery stenosis treated and followed at our institution from January 2009 to December 2023 were included in this study: 198 ICAD lesions in 155 patients (mean follow-up 11 months) were retrospectively evaluated. Each patient was divided into antiplatelet therapy alone (AA) (monotherapy (MT) or CT), antiplatelet therapy plus statin (AS), and antiplatelet therapy plus statin and EPA (AE). Antiplatelet drug monotherapy was aspirin, clopidogrel, or prasugrel and combination therapy was any of them plus cilostazol. ICAD was assessed by MRA and the stenosis rate was calculated by the warfarin-aspirin symptomatic intracranial disease (WASID) method.Results:The improvement in stenosis was significantly better with CT than with MT (Median% interquartile range(IQR)= CT: 21.71% (11.33-41.40) vs. MT: 9.15% (2.69-25.78), P

Stroke, Volume 56, Issue Suppl_1, Page A98-A98, February 1, 2025. Background:Middle cerebral artery steno-occlusive disease (MCAD) has been recognized as a different clinical entity from moyamoya disease (MMD). Although MCAD can progress to MMD, the extent to which patients actually progress and the risk factors for this progression have not been fully elucidated.Methods:We retrospectively reviewed patients with MCAD who underwentRNF213genotyping. Demographic features,RNF213p.R4810K mutation, medical history, and longitudinal changes in angiography were analyzed.Results:Sixty patients with 81 affected hemispheres were enrolled. During the follow-up period 17 patients developed MMD, and theRNF213p.R4810K mutation was the only factor significantly associated with progression to MMD (odds ratio, 16.1; 95% CI, 2.13–731;P= 0.001). The log-rank test demonstrated that patients with the mutation had a higher risk of progression to MMD (P =0.007), stenosis progression (P =0.010), and symptomatic cerebral infarction or hemorrhage (P =0.026). In Cox regression analysis the p.R4810K mutation remained a significant factor after adjusting for age group (childhood or adult onset) at diagnosis (hazard ratio, 8.42; 95%CI, 1.10–64.4). Hemisphere-based analysis also showed that the mutation was associated with a higher risk of progression to the MMD hemisphere (P =0.002), stenosis progression (P =0.005), and cerebral infarction or hemorrhage (P =0.012).Conclusions:TheRNF213p.R4810K mutation was identified as a risk factor for progression from MCAD to MMD.Genotyping for this mutation may contribute to risk stratification in MCAD.

Stroke, Volume 56, Issue Suppl_1, Page ATMP44-ATMP44, February 1, 2025. Introduction:Understanding factors that contribute to missed diagnoses of acute ischemic stroke (AIS) may improve diagnostic accuracy. Prior studies have focused on the failure of non-neurologists to recognize AIS. The aim of this study was to understand the characteristics of stroke-alerted patients whose symptoms were misattributed to a stroke mimic by the responding vascular neurology team.Methods:A retrospective chart review was conducted on patients seen by the vascular neurology team as a stroke alert at a single Joint-Commission-certified Comprehensive Stroke Center between 1/2021-2/2022. Patients whose symptoms were erroneously attributed to a stroke mimic at the time of assessment but later confirmed by MRI as AIS (“missed stroke”) were compared to 200 consecutive cases of stroke patients who were correctly diagnosed (“accurate stroke”) and 200 who were correctly diagnosed with a stroke mimic (“accurate mimic”). Patient characteristics were compared with univariate analysis, using chi square or Kruskal-Wallis H test as appropriate.Results:1823 stroke alerts were reviewed to identify 40 patients with missed stroke (incidence 2.2%) of which the median age was 66 years (IQR 58-81), median NIHSS was 5 (IQR 1-18), and 40% presented within the 4.5h-treatment window for thrombolysis. Patients with missed strokes were more likely female than those with accurate strokes (57% vs 39%, p

Stroke, Volume 56, Issue Suppl_1, Page AWMP114-AWMP114, February 1, 2025. Introduction:Clonal Hematopoiesis of Indeterminate Potential (CHIP) is characterized by the expansion of a blood-cell clone due to somatic mutation in hematopoietic stem cells, in the absence of other hematologic abnormalities. Initially, CHIP was identified as a risk factor for hematologic cancer, but recently, many studies have implicated it as a risk factor for cardiovascular disease. CHIP is also considered a risk factor for subarachnoid hemorrhage. However, the causality between CHIP and aneurysm rupture, as well as the mechanism by which CHIP promotes aneurysm rupture, remains unclear. Our study aimed to assess whether CHIP promotes the development of intracranial aneurysm rupture and investigate its mechanisms in mice. We induced intracranial aneurysms on chimeric mice with partial bone marrow transplantation of TET2-knockout hematopoietic stem cells, widely used to recapitulate human CHIP to test our hypothesis.Methods:We used competitive bone marrow transplantation as a model of CHIP. We used the C57BL/6 congenic mice that express the CD45.1 allele as a recipient and TET2-knockout mice that carry CD45.2 alleles as a donor. C57BL/6 CD45.1+/CD45.2- congenic mice were transplanted with suspensions of bone marrow cells containing 10% CD45.1-/CD45.2+ TET2-/- cells and 90% CD45.1+/CD45.2- TET2+/+ cells as a TET2-derived CHIP model. We induced intracranial aneurysms by a combination of elastase injection and DOCA-salt hypertension at 8 weeks later. We evaluated the formation and rupture rates of intracranial aneurysms and the survival curve. The qPCR was used to reveal molecular change in the intracranial artery. From the result of qPCR, we utilized IL-6 monoclonal antibody and NLRP3 inhibitor as a treatment for CHIP-related intracranial aneurysm rupture.Results:First, CHIP mice show clonal expansion of TET2-knockout cells in flow cytometry (Fig.1). Our studies demonstrated increased aneurysmal rupture rates in CHIP mice of both sexes (Fig.2). Second, Inflammatory cytokines including IL-6, IL-1β, and NLRP3 were elevated in qPCR (Fig.3). Lastly, both IL-6 monoclonal antibody and NLRP3 inflammasome inhibitor significantly decreased aneurysm rupture rate in CHIP mice.Conclusions:Our study showed that CHIP promotes the development of intracranial aneurysm rupture. Its mechanism is through the upregulation of inflammatory cytokines. Our findings suggest that IL-6 and NLRP3 are promising therapeutic targets for CHIP-related intracranial aneurysm rupture.

Stroke, Volume 56, Issue Suppl_1, Page A90-A90, February 1, 2025. Introduction:Post-Stroke Cognitive Impairment (PSCI) is increasingly recognized as a major factor in long-term disability. Therefore, new therapies that enhance post-stroke brain function (plasticity) are appealing in translational research. Activation of the cation channel TRPM2 after middle cerebral artery occlusion (MCAO) induces PSCI-like symptoms, such as memory impairment and deficits in Long-Term Potentiation (LTP). Determining the mediator of chronic TRPM2 channel activation may implicate a novel contributor to LTP deficit. The enzyme CD38 may be this mediator, as it produces the TRPM2 activator ADPr. Here, we investigate astrocytic CD38’s role in MCAO and TRPM2-induced deficits.Methods:LTP was assessed through Extracellular Field Recordings from CA3-CA1 synapses of Acute Hippocampal Slices. Immunofluorescence stained for GFAP and CD38 in hippocampal sections. Wt or CD38-/-mice were subjected to 60-minute MCAO, or Sham, and assessed for LTP 7 days later. Wt or TRPM2-/-mice received Intracranial Administration (200nL, 1012gc/mL) of AAV-CD38-eGFP (astrocyte CD38 overexpression) or AAV-eGFP (control) to the right ventral CA1 and assessed for LTP after 21 days. All mice were 8-12-week-old males. Differences between groups were determined with either Welch’s T-Test or One-Way ANOVA followed by post-hoc test.Results:We observed increased expression of CD38, colocalized with GFAP (astrocyte marker), in the hippocampus 7 days post-MCAO. Sham Wt mice exhibited robust LTP, not observed in Wt MCAO (Wt-Sham: 176% +/- 33.9 vs Wt-MCAO: 135% +/- 23, p < 0.05). Conversely, CD38-/-mice displayed robust LTP after either Sham or MCAO, depicting protection of synaptic plasticity (CD38-/--Sham: 175.2% +/- 24.1, CD38-/--MCAO: 184.8% +/- 27.3). AAV-CD38-eGFP astrocytic overexpression vector produced impairment in LTP in the Wt mice compared to the empty vector control (Wt-eGFP: 195.6% +/- 46 vs Wt-CD38:141.5% +/- 38.7, p < 0.05). No differences were observed in TRPM2-/-mice injected with either virus. (TRPM2-/--eGFP: 180.3% +/- 39.4, TRPM2-/--CD38 174% +/- 54.1)Conclusions:Our study implicates astrocytic CD38 as a novel inducer of hippocampal synaptic plasticity impairment. CD38 is increased following injury and required for MCAO-induced LTP deficit. Additionally, overexpression is sufficient to impair LTP in uninjured mice, in a TRPM2-dependent manner. Astrocytic CD38 is a novel target for PSCI and the likely upstream mediator of chronic TRPM2 activation.

Stroke, Volume 56, Issue Suppl_1, Page AWP194-AWP194, February 1, 2025. Introduction:A semi-automated method that compares voxel density with the contra-lateral hemisphere to generate ratio, or relative Non-Contrast CT (rNCCT) maps for identifying hypodensity changes was developed. In addition to being sensitive to stroke related hypodensities, these maps are also sensitive to motion artefacts and naturally occurring asymmetry in densities across hemispheres. We assessed the value of a deep-learning based model to segment and remove these artefacts and for identifying ischemic core of baseline NCCT.Methods:We included data from 268 acute ischemic stroke patients with a large vessel occlusion from the ongoing CT perfusion to Predict Response to Recanalization in Ischemic Stroke Project 2 study. NCCT scans acquired at the primary stroke center were used to create rNCCT maps. These maps detect regions with at least 1% relative hypodensity difference compared to the contralateral region. A trained observer who had insight of arterial occlusion location manually annotated artefacts. We trained ano new UNetusing the NCCT, rNCCT, and flipped NCCT images to detect artefacts from the rNCCT maps. To assess the extent to which our model falsely identified ischemic regions as artefact, we determined the overlap between the automatically segmented artefact on the rNCCT map and the manually segmented ischemic core on diffusion-weighted imaging (DWI) acquired at the comprehensive stroke center before treatment.Results:The best performing model was the ensemble of the five cross-validation folds of 3d low- and high-resolution models based on dice similarity coefficient. Figure 1 provides an example of our model’s artefact segmentation and the processed rNCCT map after artefact removal. For the 54 patients (20% of study population) in our test set, our model achieved a median Dice similarity coefficient of 0.95 (IQR: 0.91-0.97) and a median false positive volume of 6.1 (3.2-11) ml. In the 30 patients with available DWI scans, 30% of patients had any overlap ( >=1 voxel) between the segmented artefact and DWI ischemic core with a median overlap volume of 0.69 (IQR: 0.32-2.3) ml.Conclusion:We demonstrate the use of a deep-learning based model to automatically segment artefacts from rNCCT maps. Our model circumvents time-invasive manual removal of artefacts from the rNCCT map and thereby simplifies segmentation of the ischemic core on baseline NCCT. Validation with external datasets is necessary before use in routine stroke evaluation.

Stroke, Volume 56, Issue Suppl_1, Page AWMP110-AWMP110, February 1, 2025. Background:Stroke induced disruption of the blood-brain barrier (BBB) exacerbates neurovascular damage. Emerging data show that deficiency of endothelial β-catenin contributes to stroke-induced BBB disruption and hemorrhagic brain injury. However, whether activation of β-catenin in cerebral endothelial cells (CECs) alleviates stroke induced neurovascular damage is unknown. Using transgenic mice with CEC specific activation of β-catenin, the present study investigated whether enhancement of CEC β-catenin activity reduces neurovascular damage after stroke.Methods:A transgenic mouse line with inducible CEC specific expression of a stable β-catenin mutant (CEC-Ctnnb1 mice) was generated by crossing Slco1c1-CreERT2mouse with Ctnnb1flex3mouse. Tamoxifen (TAM) was injected for 5 days to active Cre recombinase. Western blot was performed to verify β-catenin activation in the adult CEC-Ctnnb1 and their wild-type (WT) littermates (n=6/group) after termination of TAM. Male CEC-Ctnnb1 and WT mice treated with TAM were subjected to permanent middle cerebral artery occlusion (MCAO, n=10/group). Neurological function was evaluated with modified neurological severity score and foot-fault test at 1 and 7 days after MCAO. Brain tissues were processed for evaluations on infarct volume, gross hemorrhage, vascular leakage, and tight junction protein expression.Results:Immunohistochemistry and Western blot analyses revealed nuclear β-catenin expression specifically in the CECs of CEC-Ctnnb1 mice, but not in the WT mice, which was associated with significant elevation of β-catenin regulated the tight junction proteins, claudin 5 and ZO-1 by ~2 fold, compared to the WT mice. The ischemic CEC-Ctnnb1 mice exhibited significantly reduced infarct volume (16±5% vs 25±6% in WT), which was associated with a robust reduction of neurological deficits by 35% and 53% at 1 and 7 days after MCAO, respectively. Compared to the WT ischemic mice, ischemic CEC-Ctnnb1 mice exhibited significant increases of vascular claudin-5 by 45% and ZO-1 by 31%, which were associated with a significant reduction of extravascular fibrin deposition (5±1/mm2vs 8±1/mm2in WT). However, the incidence of gross hemorrhage was not different between the groups.Conclusions:The activation of β-catenin in CECs attenuates ischemic brain damage by alleviating stroke induced cerebrovascular disruption. Thus, targeting endothelial β-catenin signal may be a promising strategy for treatment of acute ischemic stroke.

Stroke, Volume 56, Issue Suppl_1, Page AWMP105-AWMP105, February 1, 2025. Introduction:Accurate prediction of the risk of ischemic stroke (IS) is vital for prevention and would be aided by multimodal biomarkers integrating genetic, clinical, and functional data. The role of imaging and EKG based atrial measurements, other than atrial fibrillation (AF), in IS prediction is uncertain and many strokes remain cryptogenic despite extensive work-up. As an exploratory step to improve stroke evaluation by including atrial traits, we developed a novel multimodal deep learning model integrating demographic and clinical variables with atrial phenotypic and genotypic data.Methods:We collected individuals from UK Biobank (UKBB) and defined ischemic stroke (IS) by the UKBB Algorithmically Defined Outcome (ADO). We developed a multimodal multi-layer perceptron with late fusion (MMLP-LF) model to predict whether a subject has IS by integrating five data modalities from UKBB: 1) MRI and EKG derived atrial traits, 2) lead genetic variants (P

Stroke, Volume 56, Issue Suppl_1, Page ATP355-ATP355, February 1, 2025. Background:Neutrophil Extracellular Traps (NETs) are web-like structures of DNA, histones, and granule proteins that trap pathogens as part of innate immunity but also scaffold red blood cells, fibrin, and platelets in pathological thrombosis. Thrombus NETs have been associated with failed thrombolysis and thrombectomy for acute ischemic stroke (AIS). We previously used mass spectrometry to describe a novel association between NET proteins and atrial fibrillation (AF). This association has not been validated by traditional immunohistochemical methods.Aims/Purpose:We used immunohistochemistry to quantify NETs in AIS thrombus taken from patients with and without comorbid AF.Methods:We selected markers for each of the components of NETS: (1) a granule protein, myeloperoxidase (MPO), (2) citrullinated histone 3 (CitH3), and cellular nucleic acid (NA, using Hoechst 33342). This was a single-blind study using cryopreserved thrombi from 30 patients, 15 with AF. Stroke thrombi were collected over a two-year span, and immediately frozen to -80*C post-thrombectomy. To capture the coverage of NET markers more comprehensively for each patient, we used cryostat to sample four sections (five-micron thickness) from each thrombus. We then fixed sections with 4% formaldehyde in phosphate buffered saline (PBS), performed immunohistological staining, and quantified extent of staining using ImageJ. Data for each NET marker from a single thrombus is represented as the mean percentage of thrombus area staining positively across the four corresponding sections. After performing Shapiro Wilks test for normality, statistical comparisons of NET marker staining coverage between AF and non-AF thrombi were performed with either unpaired T test or Mann-Whitney U test, depending on whether a parametric or non-parametric test was appropriate.Results:Thrombi from patients with AF had greater MPO coverage(17.9 +/- 1.47% versus 11.6 +/- 1.29% in non-AF, p

Stroke, Volume 56, Issue Suppl_1, Page ATMP69-ATMP69, February 1, 2025. Introduction:Cerebral Amyloid Angiopathy (CAA) is caused by the progressive deposition of β-amyloid in the walls of small to medium-sized cerebral vessels. Although seizures represent a debilitating manifestation of CAA, little is known about their prevalence or associated factors. We aim to fill this gap by determining the prevalence of seizures in CAA and identify factors associated with an increased risk of seizures.Methods:We identified consecutive patients with CAA, evaluated within the Mayo Clinic health system between January 2010 and December 2023 using the ICD-10 code. Data on demographics and comorbidities were compared between those with and without seizures using the chi-square test for categorical variables and independent samples t-test for continuous variables. Odds ratios (OR) were estimated after adjusting for age, sex, and race in multivariable logistic regression.Results:We included 1,914 patients with CAA with a mean age of 75.4 ± 8.6 years, of whom 52.3% were female and 87.5% were white. Seizures were observed in 347 patients (18.1%). Individuals with seizures were significantly younger (mean age 67.7 ± 9.1 vs. 77.2 ± 7.5 years, p < 0.001). Multivariable modeling identified alcohol abuse (OR 1.92, 95% CI 1.03-3.56, p=0.04), diabetes mellitus (OR 2.14, 95% CI 1.13-4.06, p=0.02), hypertension (OR 1.79, 95% CI 1.33 - 2.41, p=