Abstract WMP47: Exploring the Neural Mechanism of Post-Thalamic Stroke Apathy Based on Disconnection-Symptom Mapping Analysis

Stroke, Volume 56, Issue Suppl_1, Page AWMP47-AWMP47, February 1, 2025. Background:Occurrence of post-stroke apathy (PSA) is associated with worse outcomes and poorer quality of life. Particularly, post-thalamic stroke apathy was repeatedly reported. In this study, we performed disconnection-based analyses to reveal the neural basis of post-thalamic stroke apathy from both focal and network perspectives.Method:This study recruited first-ever unilateral thalamic ischemic stroke patients. The Lille Apathy Rating Scale was used to characterize the appearance and severity of apathy. Patient’s lesion masks were embedded into normative connectome to generate functional or structural disconnection maps. Support Vector Regression-based Multivariate Lesion-Symptom Mapping and Disconnection-Symptom Mapping were employed to explore associations between lesion locations, structural and functional disconnections, and PSA.Results:A total of 92 patients with thalamic infarction were included. No significant associations were found between thalamic lesion locations and PSA. However, structural disconnection in the anterior thalamic radiation and functional disconnection in the bilateral medial prefrontal cortex, bilateral inferior frontal gyrus, bilateral anterior insular cortex, right inferior parietal lobule, and right superior temporal gyrus were significantly associated with PSA.Conclusion:The study revealed that apathy following thalamic ischemic stroke is associated with disruptions in thalamocortical networks rather than specific lesion locations. These findings suggest that post-thalamic stroke apathy is a network disorder, driven by functional diaschisis and secondary neurodegeneration. Understanding these mechanisms may inform treatment targets and improve post-stroke rehabilitation strategies.

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Gennaio 2025

Abstract WP335: CT Perfusion for Predicting Ischemic Stroke in Patients with Symptomatic Carotid or Middle Cerebral Artery Occlusion: A Post-hoc Analysis of the CMOSS Study

Stroke, Volume 56, Issue Suppl_1, Page AWP335-AWP335, February 1, 2025. Objective:We aim to test the ability of CT perfusion (CTP) for predicting ischemic stroke in patients with symptomatic chronic carotid or middle cerebral artery occlusion.Methods:This was a post-hoc analysis of the CMOSS trial (NCT01758614), a randomized controlled trial comparing extracranial-intracranial (EC-IC) bypass surgery to medical therapy in patients with symptomatic carotid or middle cerebral artery occlusion and hemodynamic insufficiency measured by CTP. Patients treated with medical treatment alone in the trial were included. Mean transit time (MTT) and relative cerebral blood flow (rCBF) from CTP were collected. The primary outcome was defined as ischemic stroke in the territory of the qualifying artery within 2 years after randomization.Results:All 165 per-protocol patients (median age = 53.7 years, 81.2% males) treated with medical treatment alone were analyzed. Sixteen patients (9.7%) suffered from ischemic stroke in the territory of the qualifying artery during two-year follow-ups. Cut-off values of MTT >6.5s (symptomatic side) and rCBF ≤0.5 were suggested to be associated with recurrent stroke. In multivariate Cox regression, MTT (adjusted hazard ratio [HR] = 3.50, 95% CI = 1.19-10.30, p = 0.02) and rCBF (adjusted HR = 7.36, 95% CI = 2.27-23.85, p =0.001) were independently associated with the primary outcome.Conclusion:This study demonstrated CTP-based hemodynamic evaluation had relative accuracy in predicting recurrent ischemic stroke in symptomatic patients with chronic carotid or middle cerebral artery occlusion, which can be potentially used in patient selection for stratified secondary prevention of stroke. Future studies are warranted to verify current findings.

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Gennaio 2025

Abstract WP367: Attenuating Post-stroke Ischemia Reperfusion Injury: Establishing the Efficacy of Disodium Malonate in a Clinically Relevant Sheep Model

Stroke, Volume 56, Issue Suppl_1, Page AWP367-AWP367, February 1, 2025. Introduction:Ischemia reperfusion injury (IRI) is a paradoxical and deleterious consequence of current interventions for acute ischemic stroke (AIS). Rapid restoration of oxygen to brain tissue upon reperfusion initiates mitochondrial reverse electron transport (RET) and production of reactive oxygen species (ROS), which exacerbate cell death. A pivotal role of the citric acid cycle intermediate succinate has been identified in driving RET post-reperfusion, whereby succinate accumulated during ischemia is rapidly reoxidized following reperfusion leading to a burst of ROS. Disodium malonate (DSM), a competitive inhibitor of succinate dehydrogenase, has been shown to attenuate RET ROS production following reperfusion and reduce infarct volume in rodent models. Here, we sought to evaluate the effect of DSM on infarct evolution post-reperfusion in a clinically-relevant sheep model of AIS for enhanced clinical translation.Methods:Male Merino sheep (N=13, 24-36 months, 62±6 kgs) underwent right pterional craniotomy and middle cerebral artery occlusion (MCAo) via aneurysm clip application for 4 hrs followed by reperfusion. Animals were pre-operatively randomized into vehicle (0.9% saline, N=5), medium dose DSM (0.5 mmole/min; N=4) and high dose DSM (1.0 mmole/min; N=4). Treatment was administered via right common carotid catheter at a rate of 15 mL/min for 10 min, starting 5 min prior to reperfusion. MCAo and reperfusion were confirmed on digital subtraction angiography (DSA). One hour following reperfusion, animals underwent magnetic resonance imaging (MRI) with a follow-up MRI performed 6 hours later. Infarct volume was calculated on diffusion weighted imaging (DWI) at each time-point to assess ischemic evolution.Results:All animals displayed evidence of MCAo and successful reperfusion following aneurysm clip removal (Figure 1). Infarct volume between groups was comparable at 1 hr post reperfusion (P >0.05), however, by 6 hrs infarct expansion was attenuated in animals receiving DSM compared with vehicles (P=0.0037). This was apparent in both the medium (P=0.006) and high (P=0.011) DSM groups.Conclusions:Intraarterial DSM administration reduces infarct expansion following reperfusion in a sheep model of MCAo. Evaluation of treatment efficacy in a larger cohort of animals is essential to address stroke therapeutic and industry roundtable (STAIR) guidelines and provide evidence to progress DSM to clinical trial for the treatment of IRI in AIS.

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Gennaio 2025

Abstract WP356: Use of MicroRNA as a Prospective Biomarker for Post-Stroke Socially Isolated Patients

Stroke, Volume 56, Issue Suppl_1, Page AWP356-AWP356, February 1, 2025. Introduction:Blood-based biomarker investigations for neurological diseases such as ischemic stroke are commonly used in clinical practice and traditionally have focused on measuring alterations in cytokine quantity and composition. An emerging area has been the use of microRNA studying the effects of gene expression after ischemic stroke. There has been extensive evidence that gene expression changes after ischemic injury, especially in gene pathways related to inflammatory response, vascular injury, and cellular degeneration. Establishing a reliable blood-based biomarker used to quantify clinical indications is necessary for emergent treatment. With a blood-based assessment that utilizes transcriptomics, healthcare providers can better understand post-stroke molecular changes more rapidly, which is crucial during this acute phase.Methods:Peripheral blood samples were collected from ischemic stroke patients (N=100) during the acute onset of disease, 24 hours after the last known well. In this study, we investigated possible differences among the stroke population based on risk factors including age, sex, race, social isolation status, and presence of cognitive impairment. For this analysis, overall social isolation status was defined by a mixed model matrix comprised of Lubben Social Network score and UCLA Loneliness score. We used whole transcriptomic sequencing to assess these variables.Results:Overall, there were 8 miRNA sequences significantly upregulated in socially isolated patients. There were no significant differences found among patients based on sex or age variability. Interestingly, we found that circulatory miR-24-3p (FDR adjusted p-value

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Gennaio 2025

Abstract WP123: Exploring Myasthenia Gravis as a Potential Contributor to Post-Stroke Fatigue: A Prospective Case-Control Study

Stroke, Volume 56, Issue Suppl_1, Page AWP123-AWP123, February 1, 2025. Background:Post-stroke fatigue is a common and debilitating issue, often linked to depression or neural damage. Emerging evidence suggests that myasthenia gravis (MG) may also play a role in post-stroke fatigue, offering a new perspective on patient management and long-term disability reduction.Objectives:This study aims to assess the incidence of de novo MG in stroke survivors following motor recovery over 18 to 24 months and compare findings with a healthy control group.Methods:Conducted at a tertiary care institution over two years, this prospective case-control study included ischemic and hemorrhagic stroke patients. Participants were recruited during the acute stroke phase and underwent evaluations for neuromuscular weakness and autoimmune disorders. They were monitored in a specialized stroke clinic for two years. Key variables included demographics, comorbidities, autoimmune disorders, stroke subtype, time since onset of stroke, and muscle fatigability. Age and sex-matched controls were assessed concurrently. Baseline and two-year follow-up measurements of acetylcholine receptor (AChR) antibodies were performed, and new antibodies were monitored. Participants with significant fatigability were tested for MG, and if confirmed, treated with cholinergic drugs.Results:The study involved 96 participants with a mean age of 60.45 years, predominantly male (63.86%). Ischemic stroke was most common (93.75%). Major risk factors included hypertension (12.5%), diabetes (5.20%), and dyslipidemia (3.12%), with 11.45% having autoimmune disorders. Of the 96 participants, 74 (77.08%) reported fatigability an average of 23.2 months post-stroke. Types of fatigability included neck (34.37%), proximal arm (11.46%), grip (19.80%), speech (5.21%), and eye (6.25%). Among 36 stroke patients with post-stroke fatigability and 36 controls re-evaluated at follow-up, 7 stroke patients tested positive for AChR antibodies compared to 1 control. Fisher’s Exact test showed a significant association between stroke and AChR-Ab positivity (p = 0.001), with an odds ratio of 7, suggesting a potential link between post-stroke fatigue and MG.Conclusion:The study highlights MG as a potential underrecognized factor in post-stroke fatigue. These findings may improve diagnostic and therapeutic strategies for stroke survivors and pave the way for further research into post-stroke immune alterations and MG development.

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Gennaio 2025

Abstract WP130: Sexual Dysfunction Education and Treatment Post Stroke

Stroke, Volume 56, Issue Suppl_1, Page AWP130-AWP130, February 1, 2025. Introduction:Over half of stroke patients experience sexual dysfunction as a result of an ischemic or hemorrhagic stroke. Stroke survivors establish that sexual activity and sexual expression are fundamental activities of daily living. Yet, sex education and treatment are not a primary component of post-stroke treatment and rehabilitation. The purpose of this research is to validate the need for sexual dysfunction education and treatment following a stroke and to identify and address barriers to receiving the needed education.Methods:Interviewed local stroke survivors and their significant others. Interviewed interdisciplinary in-patient and out-patient treatment team members including physicians, nurses, occupational therapists and physical therapists. Compared the stroke survivors’ post-stroke deficits to the education received from healthcare providers. Researched sexual dysfunction educational resources available for both healthcare providers and stroke survivors. Researched importance of sexual activity and sexual expression to a person’s quality of life.Results:Seventy-six percent of people age 57 – 80 believe that sex is an important aspect of a romantic relationship. Greater than 50% of stroke survivors experience sexual dysfunction. Healthcare providers seldom provide education on sexual dysfunction following a stroke because of limited resources, prioritizing other functional limitations (feeding, dressing, mobility) and a reluctance to discuss.Conclusions:In conclusion, sexual dysfunction education and treatment are essential to the quality of life of stroke survivors and their significant others. Despite sexual activity and sexual expression being a fundamental activity of daily living, education and treatment for sexual dysfunction following a stroke is very limited. Effective educational materials and training will empower healthcare providers to successfully address sexual dysfunction and improve their patients’ quality of life.

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Gennaio 2025

Abstract WP369: Peripheral CD200R Signaling: A Critical Regulator of Post-Stroke Inflammation

Stroke, Volume 56, Issue Suppl_1, Page AWP369-AWP369, February 1, 2025. Background:Immune responses are fundamental to ischemic stroke pathology. Controlling pro-inflammatory responses helps reduce brain ischemic injury and has translational significance. The interaction between CD200R, an inhibitory receptor on immune cells, and the CD200 ligand suppresses pro-inflammatory pathways. The accumulating data have suggested that CD200R is minimally expressed on adult microglia after stroke, suggesting an inhibitory role of the CD200-CD200R axis in mobilization of peripheral immune cells.Hypothesis:CD200-CD200R signaling in peripheral leukocytes is more essential than the central (brain) signaling to post-stroke inflammation and outcomes.Methods:CD200R global knockout (KO), GFP, and C57BL/6 wild-type (WT) male and female (16-20 months) were used to generate 3 types of bone marrow chimeric (BMC) mice: GFP-to- KO (central signaling), KO-to-GFP (peripheral), and GFP-to-WT (control). All chimeras underwent a 60-minute transient middle cerebral artery occlusion (MCAO). Three days after stroke, neuroinflammation was evaluated by flow cytometry (FC; for leukocyte infiltration), and brain/plasma ELISA (cytokines). Stroke outcomes, including infarct volume and neurobehavioral deficits, were also assessed.Results:We have validated the three BMC models by FC (Fig. 1). FC analysis further revealed significantly more infiltration of immune cells into ischemic brains of KO-to-GFP vs. control mice; whereas no difference was seen in GFP-to-KO vs. control group. Brain and plasma ELISA data indicated significantly higher levels of pro-inflammatory cytokines (TNF-α, IL-1β) in the KO-to-GFP vs. control mice. Additionally, KO-to-GFP mice demonstrated larger infarct sizes, more severe neurological deficit scores (NDS), and greater motor impairments in the open field test (OFT) and grip strength assessment.Conclusions:Peripheral CD200R signaling (but not the central signaling) impacts on post-stroke inflammation and outcomes. Our data highlight a potential therapeutic target for mitigating stroke injury by modulating peripheral CD200-CD200R axis.

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Gennaio 2025

Abstract WP145: Neighborhood Economic and Demographic Landscape as Predictors of 90 Days Outcomes Post Stroke Hospitalization

Stroke, Volume 56, Issue Suppl_1, Page AWP145-AWP145, February 1, 2025. Objective:A thorough exploration of neighborhood environmental impacts on post-discharge stroke outcomes is lacking and crucial to identifying populations at high risk. We assess neighborhood economic and demographic characteristics associated with 90-day death or readmission post-stroke hospitalization.Methods:The study population included 1329 stroke survivors in the prospective Florida Stroke Registry’s Transition of Care Stroke Disparities Study (91% ischemic stroke, 56% males, 51.5% Non-Hispanic White, 22.6% non-Hispanic Black, 21.8% Hispanic, median age 64). Publicly available data on the neighborhood (Zip+4) characteristics included socioeconomic status (NSES), race/ethnic composition, and business densities (food, tobacco/alcohol, gyms, medical services), which were used in factor analysis to create four main factors. Structured telephone interviews at 90 days post-discharge assessed stroke outcomes (death or readmission). Logistic regression models examined associations between the neighborhood characteristics and death/readmission, adjusting for individual demographics (race/ethnicity, sex, age), vascular risk factors and stroke severity obtained from Get with the Guidelines-Stroke®, and individual social/economic conditions (insurance, social support, living arrangement) from patient interviews.Results:Within 90 days post-discharge, 208 patients experienced death or readmission. Four main factors explained 56% of the variance in 24 neighborhood characteristics, of which factor 1 was associated with a 20% increased risk of death/readmission. Factor 1 was characterized by Hispanic dominance (above median %Hispanic), lower NSES (higher %below the poverty line, densely populated), and highly urbanized (primary Rural-Urban Commuting Area (RUCA) code of 1, higher densities of tobacco outlets, alcohol outlets, restaurants, grocery stores, gyms, and pharmacies).Conclusions:Living in predominantly Hispanic, highly urbanized, crowded neighborhoods with lower SES, predicted poor stroke outcomes independent of individual health or SES conditions. These findings can help inform the target population for community interventions aimed at improving stroke mortality and readmission rates.

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Gennaio 2025

Abstract WP127: Impact of High Intensity Interval Training on Neuropsychiatric Disorders and Serum BDNF Levels Post-Stroke. A Systematic Review and Meta-analysis

Stroke, Volume 56, Issue Suppl_1, Page AWP127-AWP127, February 1, 2025. Introduction:Cognitive impairment, mood disorders, and reduced serum BDNF levels are common in stroke patients. Previous studies suggest that aerobic exercise improves these outcomes by enhancing oxygenation. Herein, the authors compare the effectiveness of high-intensity interval training (HIIT) with low (LIT) and moderate (MIT) intensities and usual activity (UA) in stroke patients.Methods:We systematically searched PubMed, Cochrane, Embase, and Scopus databases for studies comparing HIIT with LIT, MIT, or UA in stroke patients. We evaluated change from baseline in cognitive improvement, mood disorders including anxiety and depression, and serum BDNF levels. Subgroup analyses were conducted based on stroke onset and exercise intensity, and separate analyses compared HIIT with each control group to assess cognitive improvement at different intensity levels.Results:A total of ten non-randomized and randomized studies were included in the analysis. Seven studies involving 373 patients showed no statistically significant difference in cognitive improvement between HIIT and the control group (std. MD 0.09; 95% CI -0.13 to 0.30; p=0.43). Separate analyses also revealed no significant differences between HIIT and LIT (std. MD -0.06; 95% CI -0.54 to 0.41; p=0.60), HIIT and MIT (std. MD 0.03; 95% CI -0.30 to 0.37; p=0.85), and HIIT and UA (std. MD 0.20; 95% CI -0.13 to 0.53; p=0.23). Subgroup analysis for chronic stroke did not show significant differences either (std. MD 0.07; 95% CI -0.19 to 0.34; p=0.58). Additionally, an analysis of four studies involving 281 patients found no significant difference in mood disorders (std. MD -0.21; 95% CI -0.62 to 0.21; p=0.33). A separate analysis of four studies with 130 patients also revealed no significant difference in serum BDNF levels between the two groups (std. MD 3.65; 95% CI -0.37 to 7.67; p=0.08). However, subgroup analysis indicated that serum BDNF levels were 3.32 ng/mL higher in the MIT group compared to the HIIT group.Conclusion:High-intensity-interval training does not demonstrate a significant advantage in cognitive improvement, mood disorders, or serum BDNF levels when compared to different exercise intensities. However, MIT is associated with increased serum BDNF levels compared to HIIT. Future robust RCTs are needed to compare different exercise intensities and durations to provide more conclusive results.

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Gennaio 2025

Abstract WP146: Racial Differences in Percutaneous Endoscopic Gastrostomy (PEG) Placement in Post-Stroke Dysphagia

Stroke, Volume 56, Issue Suppl_1, Page AWP146-AWP146, February 1, 2025. Background:Prior literature has reported patterns of racial differences in percutaneous endoscopic gastrostomy (PEG) placement for patients with post-stroke dysphagia. Reasons for this disproportion are not well understood, but critical for clinical decision making. Long-term implications for PEG placement are considerable, given complication rates and that reducing oral intake can significantly impact recovery of swallow function. In this population-based study, we evaluated the influence of patient-related factors and stroke characteristics on PEG placement.Methods:All patients, 18 years or older, hospitalized with either ischemic or hemorrhagic stroke in Greater Cincinnati in 2010, 2015, and 2020 were considered for this study. Patients who died within 3 days or transferred to hospice care were not included. Demographics and clinical characteristics of Black and White individuals were compared. Multivariable logistic regression was then used to examine the association between Black race and PEG placement after adjustment for potential confounders. Univariable and multivariable logistic regression analysis (dependent = PEG) was used to determine influential factors for PEG placement. Patient and stroke characteristics between Black and Non-Black patients were compared using Chi-square tests, two-sample t-tests, or Wilcoxon rank-sum tests.Results:The final sample included 2315 cases, of whom 28.2% were Black (653/2315) and 54.1% were women (1254/2315). Black individuals with stroke were younger (p

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Gennaio 2025

Abstract WP377: Long-term post-stroke cognitive dysfunction in aged subjects is associated with increased synapse pruning by reactive astrocytes

Stroke, Volume 56, Issue Suppl_1, Page AWP377-AWP377, February 1, 2025. Background and Purpose:Aged patients experience more cognitive dysfunction than young patients after stroke. Brain astrocytes and microglia causes excessive removal of synapses at the early stage of stroke. Inhibition of their phagocytosis improved neurobehavioral outcomes. Long-term post-stroke cognitive dysfunction in aged subjects may be associated with increased synapse pruning by astrocytes, as increased reactive astrocytes are present in and around the atrophic region.Hypothesis:Excessive synapse pruning by reactive astrocytes contributes to the long-lasting post-stroke memory dysfunction in aged mice.Methods:pMCAO was induced in young (2-month-old) and aged (15-18-month-old) mice. Memory performance was tested weekly for 8 weeks by Y-maze, and at 8 weeks post-stroke by novel objective recognition (NOR) tests. Brains were collected 8 weeks after pMCAO. Gene expressions were analyzed by RNAseq and western blot. Atrophic volume, CD68+cells, GFAP+cells, and synaptophysin (SYP) were analyzed histologically.Results:In Y-maze test, aged stroke mice made fewer spontaneous alternations from 3 to 8 weeks after pMCAO than young stroke and sham operated aged mice. In NOR test, aged stroke mice spent shorter time on the novel objects than young stroke and sham aged mice. RNAseq data showed up-regulation of inflammation, and down-regulation of axon growth and synaptic transmission pathways in the aged ipsilateral than young ipsilateral cortex and aged contralateral cortex. Glutamatergic and cholinergic synapses were decreased in aged ipsilateral cortex and hippocampus. GABAergic presynapse protein was increased in the aged ipsilateral hippocampus compared to the young mice. All support reduced activity in the cortex and hippocampus of aged stroke mice. Aged mice showed larger atrophic volumes, more CD68+and GFAP+cells in the peri-atrophic and hippocampi regions than young mice. About 10-fold more GFAP+cells were detected in aged peri-atrophic and ipsilateral hippocampi regions than CD68+cells; 57% GFAP+and 37% CD68+cells were SYP+in the ipsilateral hippocampi, 53% GFAP+and 39% CD68+cells were SYP+in the peri atrophic region of aged stroke brain, indicating that reactive astrocytes contributed more than microglia on synapse pruning in aged mice.Conclusions:Reactive astrocytes contribute more than microglia to synapse pruning at the chronic stage of stroke, which is involved in long-lasting post-stroke memory dysfunction in the aged mice.

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Gennaio 2025

Abstract WP164: Creating an Acute Sleep Medicine Service for Veterans Hospitalized with an Acute Ischemic Stroke or Transient Ischemic Attack – A Comparative Case Study from the Addressing Sleep Apnea Post-Stroke/TIA Hybrid Type I Stepped-Wedge Cluster Randomized Trial

Stroke, Volume 56, Issue Suppl_1, Page AWP164-AWP164, February 1, 2025. Introduction:Rates of guideline-concordant obstructive sleep apnea (OSA) testing among those with a recent cerebrovascular event are exceedingly low. Understanding the role contextual factors play is necessary to inform successful implementation of quality improvement (QI) initiatives designed to address this gap in stroke/transient ischemic attack (TIA) care.Methods:Longitudinal data was collected via questionnaires and semi-structured interviews to evaluate the implementation of QI initiatives conducted at six diverse VA Medical Centers (VAMCs) participating in Addressing Sleep Apnea Post-Stroke/TIA (ASAP), a Hybrid Type I, stepped-wedge cluster-randomized trial. Intervention components included a Systems Redesign Virtual Collaborative and data monitoring (Figure 1). Implementation strategies included external facilitation and audit and feedback. Provider- (e.g., clinical training) and systems-level contextual elements (e.g., Champion Team members and their roles) were collected. Select Consolidated Framework for Implementation Research (CFIR) constructs were rated in terms of magnitude and valence. The primary outcome of successful implementation was defined at the end of 21 months of active implementation as obtaining a Group Organizational (GO) score of ≥6 a measure of programmatic development and maturation. Comparisons of sites were conducted across contextual elements and stratified by those achieving a GO score of ≥6 (Figure 2).Results:ASAP Sites 1 through 4 obtained a GO score ≥6 (range: 7-9); across these sites, the Clinical Champion had: (1) field staff engaged in activities such as care coordination; (2) full to partial support of their local sleep personnel, and; (3) consistently positive CFIR scores values. These sites also received a greater amount of external facilitation and used a quality dashboard more often. All 4 sites created a change in health care personnel and medical center culture that stressed the importance of OSA testing soon after a cerebrovascular event occurred.Conclusions:Developing strong and consistent Champion teams who meaningfully engaged with local VAMC personnel within and across sleep medicine and stroke service lines was important for implementation success. Other key contextual factors for changing culture and creating a healthcare system wide approach to improving OSA testing for stroke/TIA patients included external facilitators and using performance data.Clinical Trials registration:NCT04322162

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Gennaio 2025

Abstract WP373: Physical Exercise Post-Cardiac Arrest Mitigates Long- and Short-Term Memory Deficits

Stroke, Volume 56, Issue Suppl_1, Page AWP373-AWP373, February 1, 2025. Cardiac arrest (CA) often leads to severe memory impairment, largely due to extensive neuronal loss in brain areas critical for cognitive function, including the hippocampus and amygdala. We demonstrated that physical exercise (PE) following asphyxia CA (ACA) mitigates contextual memory deficits in male rats. Intriguingly, this effect occurs without direct protection of the hippocampus and amygdala, as evidenced by significant cell death in both regions. Instead, PE post-ACA reduces neuronal loss in the medial septum (MS), a forebrain structure essential for regulating limbic system oscillations, and thus memory. This study aims to investigate whether PE post-ACA preserves oscillatory activity within the limbic circuitry and whether it ameliorates other forms of cognitive deficits in both sexes.Methods:Male and female rats are subjected to 8’ ACA. After 5 days of recovery, the animals undergo 5 consecutive days of treadmill running, followed by a battery of cognitive tests. Approximately one-month post-ACA, the animals are anesthetized with urethane for in vivo oscillatory recordings.Results:Having acquired fear conditioning (Figs. 1a and 1d), the animals were tested for cued fear memory and extinction two days later. Post-ACA exercised animals displayed a significant increase in freezing levels compared to non-exercised animals in response to a single re-exposure to the tone, indicating preserved cued fear memory (Fig. 1c). After continuous tone presentations, only the exercised animals displayed a significant decrease in freezing, suggesting they were able to extinguish their fear response (Fig. 1f). The Y-maze test revealed a significant increase in spontaneous alternation in exercised animals (Fig. 1g), indicating improved working memory. These outcomes were not influenced by locomotion (Fig. 1h) or anxiety (Fig. 1i), as confirmed by the open field test. We are currently performing the oscillatory recordings in different limbic system regions.Conclusion:PE post-ACA mitigates different forms of long- and short-term memory deficits in both sexes. This improvement is likely mediated by the preservation of oscillatory power in the MS and hippocampus (to be confirmed), highlighting a potential mechanism by which PE exerts its neuroprotective effects.

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Gennaio 2025

Abstract WP140: Early Post Acute Care Pathways are Predictive of 1-Year Home Time among Patients with Acute Ischemic Stroke: Analysis of Clinical and Claims Linked Data

Stroke, Volume 56, Issue Suppl_1, Page AWP140-AWP140, February 1, 2025. Background:Maximizing long-term home time (HT) for acute ischemic stroke (AIS) patients has patient-centered and health-system benefits. We evaluated the influence of early (30-day) post-acute care (PAC) pathways on 1-year HT.Methods:We analyzed a cohort of Medicare AIS patients at a 7-hospital stroke certified health system (2016 to 2020). Clinical data extracted from an EMR-driven registry were linked to PAC utilization information retrieved from a CMS Qualified Entity with ≥80% data for the Texas state population (including 100% of Medicare Fee-for-Service). All claims within 1 year of hospitalization were collated and grouped into corresponding care pathways. One-year HT (i.e., number of days at home across 1-year period) was calculated utilizing discharge dates from various healthcare settings. Low HT was defined as

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Gennaio 2025

Abstract WMP91: Comparison of clinical outcomes and complications in patients undergoing Carotid Artery Stenting (CAS) with or without pre and post-stent balloon angioplasty.

Stroke, Volume 56, Issue Suppl_1, Page AWMP91-AWMP91, February 1, 2025. Background and Objective:Carotid artery stenting (CAS) is a procedure that has been established as a safe and effective alternative to carotid endarterectomy in high surgical risk patients. There are procedural questions that remain unanswered, specifically, the safety of pre-stent balloon angioplasty versus post-stent versus both. The objective of our study is to understand the risk and safety of these procedural techniques.Methods:Multicenter retrospective data related to angioplasty balloons, stents, complications due to pre and post-stent angioplasty along with the modified Rankin score (mRS) before and after the procedure were collected from January of 2015 until December of 2022. Statistical analysis was performed to correlate this data with risks of complications and clinical outcomes.Results:A total of 1355 patients were enrolled. We found that patients who underwent pre-stent angioplasty, or both (pre and post-stent angioplasty) had a higher risk of complications compared to those who only had post-stent angioplasty. There were more complications in patients who did not undergo post-stent angioplasty as compared to those who did undergo angioplasty (p=0.018, OR=0.513). Follow-up MRS at 30-90 days was higher if the balloons in both pre-stent angioplasty (p=0.016) and post-stent angioplasty (p=0.020) stent angioplasty were not inflated to nominal pressure. Follow up MRS was statistically higher (p=0.01) in patients with open-cell stents than closed-cell stents. Open-cell stents were more likely to undergo post-stent angioplasty (p

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Gennaio 2025

Abstract DP28: NLRC5 Mediates Microglial Autophagy to Regulate Post-Stroke Neuroinflammation and its Mechanisms Study.

Stroke, Volume 56, Issue Suppl_1, Page ADP28-ADP28, February 1, 2025. Background:Microglia-mediated inflammatory response directly affects ischemic stroke outcome. Autophagy is crucial in inflammatory response after cerebral ischemia. NLRC5 can be a positive or negative regulator of inflammatory signaling cascades, but its role after ischemic stroke is unstudied.Methods:Single-cell RNA sequencing and immunofluorescence staining were used to explore the expression and localization of NLRC5 in mice brain. Conditional (microglia-specific) NLRC5-knockout mice (TMEM119CreERTNLRC5f/f) and their littermate control mice (NLRC5f/f) were subjected to MCAO. Histopathological and behavioral methods were performed to assess ischemic injury in mice. In vitro, oxygen-glucose deprivation (OGD) and OGD neuronal supernatant were used to stimulate microglia to simulate post-stroke inflammatory microenvironment. Primary microglia were extracted from litters of wide type and NLRC5-global-KO mice for proteomic detection after OGD. Mass spectrometry was used to investigate the interaction of NLRC5 with other proteins. A series of cellular and molecular biological techniques were used to evaluate the proinflammatory response, autophagy activity and protein–protein interactions etc.Results:mRNA and protein expression of NLRC5 were increased after MCAO from 1 to 7 days. NLRC5 was mainly expressed in microglia rather than neurons and astrocytes. After MCAO, the cerebral infarction volume of TMEM119CreERTNLRC5f/fmice was smaller than that ofNLRC5f/fmice, and neurological impairment was slighter. In the ischemic penumbra tissue of TMEM119CreERTNLRC5f/fmice, autophagy level increased, microglia activation decreased, and inflammation decreased. In vitro experiments, NLRC5 knockdown promoted autophagy level of primary microglia and BV2 in the inflammatory environment, and the inflammatory response was reduced. Proteomic results showed that after OGD, the autophagy levels of NLRC5-global-KO primary microglia were increased compared to that of wide type mice. Additionally, the protein levels of EIF5A, EIF5A hypusination and ATG3 increased in NLRC5-KO primary microglia after OGD. Mass spectrometry revealed that NLRC5 could bind to EIF5A. Specific binding sites and mechanisms need further study.Conclusions:Down-regulation of microglia NLRC5 can increase hypusination level of EIF5A, increase ATG3 transcription, thus promote autophagy, inhibit neuroinflammation, and protect brain injury after ischemic stroke.

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Gennaio 2025