Risultati per: Stroke

Stroke, Volume 56, Issue Suppl_1, Page A19-A19, February 1, 2025. Introduction:Prior studies have shown the association between oral infection, incident stroke and atrial fibrillation (AF) a cause of cardioembolic stroke. However, the impact of preventative oral behavior such as dental flossing on stroke, cardioembolic stroke and AF are unknown. The relationship between flossing incident stroke, stroke subtypes and AF was tested in the Atherosclerosis Risk in Communities (ARIC) cohort study.Methods:In the ARIC study, home use of flossing was assessed through a structured questionnaire in visit 4 along with assessment of covariates including age, gender, race-center, hypertension, diabetes, hyperlipidemia, smoking, body mass index, education-level, regular brushing and regular dental care utilization . Outcomes were compared across index subtypes (infarction: thrombotic, cardioembolic, and lacunar strokes) using Kaplan-Meier analysis and Cox proportional hazards regression, adjusting hazards ratio (HR) for all the above covariates along with 95% confidence interval (CI).Results:In the ARIC study, 6278 dentate participants, without a prior history of stroke and 6108 without prior AF were followed for incident ischemic stroke, stroke subtypes and AF over a 25-year period. Of them 65% (N=4092 in stroke-free cohort and 4050 in AF-free cohort) reported flossing. During the follow-up period,434 were identified as having strokes, of whom 147 thrombotic, 97 cardioembolic and 95 lacunar subtypes. A total of 1291 (20%) participants were noted to have incident AF. The individuals reporting dental flossing had a lower rate of incident ischemic stroke, cardioembolic stroke and AF (Kaplan-Meier curves below). Dental flossing was significantly associated with a lower risk of ischemic stroke (adjusted HR, 0.78; 95% CI, 0.63-0.96), cardioembolic stroke subtype (adjusted HR, 0.56; 95 CI, 0.36-0.87) and AF ( adjusted HR, 0.88; 95% CI, 0.78-1.00), but not thrombotic (adjusted HR, 0.91; 95% CI, 0.63-1.32) or lacunar stroke (adjusted HR 1.09; 95% CI 0.68-1.76).Conclusion:Those reporting dental flossing have a lower risk for incident ischemic stroke, driven by cardioembolic stroke subtype and AF. The associated lower risks are independent of oral care/behavior measures such as regular brushing and regular dental care utilization, suggesting it may be a key behavior modification to emphasize in stroke risk reduction.

Stroke, Volume 56, Issue Suppl_1, Page ATP156-ATP156, February 1, 2025. Introduction:Early recognition of acute stroke and activation of emergency medical services (EMS) is a critical first step in the stroke care continuum. Failure to call 9-1-1 and other delays in seeking care contribute to prolonged prehospital delays, often limiting access to time-sensitive treatment. To identify challenges in early initiation of EMS, we sought to understand stroke survivor and caregiver perspectives on seeking acute stroke care.Methods:We conducted individual, semi-structured interviews with a convenience sample of adult stroke survivors and caregivers for patients with acute stroke that occurred in central North Carolina. In virtual interviews, participants were asked about stroke signs and symptoms experienced, their response, and care received from EMS and in the ED and hospital. Interviews were recorded, transcribed, and analyzed by two individual coders. Deductive coding and rapid thematic analysis focused on care-seeking behaviors and perspectives.Results:Of 16 interviews conducted thus far, 10 were with stroke survivors and 6 were with accompanying caregivers (14 Non-Hispanic White; 13 used EMS). Stroke onset was promptly recognized when the patient/caregiver had prior experience with stroke, exposure to stroke education, or access to healthcare professionals among their personal circles. Early stroke recognition prompted over half of the caregivers or other bystanders (spouses, adult children, or neighbors) to call 9-1-1 right away. Symptoms perceived by the patient/caregiver as a non-stroke issue (e.g., migraine, seizure) or not severe enough led a third of the participants/caregivers to delay or fail to call 9-1-1. Some participants reported being aware of EMS costs; however, none reported delaying care-seeking due to these concerns. Other concerns with calling 9-1-1 included general apprehension of medical professionals and fear of being perceived as “the boy who cried wolf.”Conclusion:Stroke survivors’ and caregivers’ perspectives highlighted accurate and early stroke recognition as a facilitator of prompt EMS initiation. Conversely, symptoms associated with other neurologic conditions or perceived as mild created delays in seeking care. Further recruitment is in progress until reaching at least 30 participants, focusing on racial and ethnic minority groups and underserved rural populations. Study findings will be used to develop effective solutions to challenges in seeking acute stroke care.

Stroke, Volume 56, Issue Suppl_1, Page A33-A33, February 1, 2025. Introduction:Net water uptake (NWU) is a novel biomarker which measures edema and tissue injury from the degree of hypoattenuation on non-contrast CT and may serve as a precision tool for predicting outcomes after acute ischemic stroke (AIS). Using our recently developed algorithm, this study aimed to evaluate the relationship between NWU and post-stroke neurologic outcomes, including language impairment and motor weakness.Methods:Consecutive patients treated for AIS at certified stroke centers in Houston, TX were included. Patients’ precise functional outcomes at hospital discharge were recorded including decreased level of consciousness, presence of language impairment, visual deficit, arm and leg weakness, need for walking assistance, and gastrostomy placement. The primary outcome for this study was the performance of calculated NWU and clinical variables to predict language impairment at discharge. Baseline characteristics were compared, and then univariate and multivariate logistic regression were used to evaluate the association between clinical variables, imaging data, and the precise neurological outcomes.Results:Among 776 patients with AIS, average age was 67.0 +/- 14.8, 47.8% were female, median NIHSS was 10 [5,18], median ASPECTS was 9 [7,10], 42.6% received tPA, and 67.1% had a large vessel occlusion (see Table 1). In univariate logistic regression, higher NWU (OR 1.45, CI 1.30-1.63) and lower ASPECTS (OR 0.68, CI 0.63-0.74) were both significantly associated with higher likelihood of language impairment and other deficits at discharge (see Table 2). Additionally, higher NWU in all ten regions was significantly associated with deficit at discharge. In multivariate logistic regression, certain clinical and imaging variables remained significantly associated as described in Table 3. The ASPECTS and NWU-based regression models were directly compared when predicting language impairment using ROC curve analysis, and areas under the curve were 0.838 vs. 0.851 respectively (p = 0.152 with Delong test, see Figure 1).Conclusion:The novel NWU biomarker was significantly associated with precise post-AIS outcomes at discharge. When controlling for confounders, NWU was non-inferior to ASPECTS. Moving forward, region-based and overall NWU will need to be studied with long-term patient outcomes. Ultimately, this novel and open-access imaging biomarker could be used in the emergency setting to guide treatment decision-making and patient counseling.

Stroke, Volume 56, Issue Suppl_1, Page ATP379-ATP379, February 1, 2025. Introduction:Rehabilitative physical therapy is essential for reducing stroke-related functional deficits; however, comorbidities may limit patient participation. Whole body vibration (WBV; 40 Hz) offers an exercise-like alternative. Our studies show that one month of post-stroke WBV reduces ischemic damage and improves motor and cognitive function in middle-aged rats. Notably, WBV significantly increased circulating irisin, a muscle-derived hormone. We hypothesize that post-stroke WBV modifies the cerebral transcriptome and irisin treatment improves stroke outcome in middle-aged female rats.Methods:Middle-aged Sprague-Dawley rats were randomized to sham or transient middle cerebral artery occlusion (tMCAO; 90 min) surgery and divided into two cohorts. A cohort received either no-WBV (steady platform) or WBV (platform vibrating at 40 Hz) for 15 minutes twice a day for a week. Cortical tissue was then collected for RNA sequencing (RNAseq) and gene enrichment analysis. The second cohort received either saline or irisin (PeproTech, 0.2 µg/g BW) treatment at 4.5 hours post-tMCAO and then once a week for a month. At 21 days post-tMCAO, rats were assessed for cognitive deficits via the Morris water maze. At 1-month post-tMCAO, brains were collected for histological analysis.Results:RNAseq revealed significant (p

Stroke, Volume 56, Issue Suppl_1, Page ATMP118-ATMP118, February 1, 2025. Introduction:Neuroanatomy-based functional examinations are crucial for understanding the extent and effects of infarcts in stroke studies. Despite the importance of correlating neurological function with brain anatomy, a comprehensive neurological score that correlates with infarction volume and location following middle cerebral artery occlusion (MCAO) in mice is lacking. During the pilot phase of the Stroke Preclinical Assessment Network (SPAN), a new scoring system—SPAN score—was developed. This study aims to evaluate the reliability and validity of the SPAN score, a 9-item tool rated on a 0-3 Likert scale.Methods:The SPAN 2.0 pilot database was utilized for analysis. Reliability was assessed using Cronbach’s alpha (α) and intraclass correlation coefficient (ICC) for individual items and the total score. Multivariate regression was performed for item selection and to determine the weight of each item. Concurrent validity was examined by correlating post-operative day 2 infarction volume, as measured by MRI, with the SPAN score.Results:The total SPAN score demonstrated acceptable reliability, with Cronbach’s α and ICC both at 0.751. Item-total correlation coefficients of each item ranged from 0.092 to 0.638. The Pearson correlation coefficient between the total SPAN score and infarction volume was 0.539. Notably, spontaneous activity showed a reversed relationship with other items; excluding this item increased Cronbach’s α to 0.766.Conclusion:The SPAN score proves to be a reliable and valid tool for neuroanatomy-based functional assessment in mouse stroke models following MCAO. Ongoing analysis will focus on refining the score by reducing the number of items, adjusting the Likert scale, incorporating lesion area, and further exploring item relationships.

Stroke, Volume 56, Issue Suppl_1, Page ATP371-ATP371, February 1, 2025. Background:Emerging evidence suggests that empagliflozin (EMPA) may offer additional benefits beyond its primary use in diabetes. Ischemic stroke is known to cause distinctive alterations in EEG signals. However, the influences of EMPA on the stroke-induced EEG changes has not been investigated. Here, we study such influences via EEG time-frequency features using the Hilbert-Huang Transform (HHT) and examine how these features correlate with the cerebral infarction.Methods:n= 47 male SD rats were randomized into 3 groups: 1] Control (n = 16, regular diet); 2] Acute EMPA treatment (n = 16, EMPA 10 mg/kg, IV given at 10 mins prior to middle cerebral artery occlusion (MCAO) and 1 min prior to reperfusion); 3] Chronic EMPA treatment (n = 15, EMPA by food, 20 mg/kg for 7 days before MCAO). To induce ischemic stroke, standard MCAO was performed for 1 hour followed by 3 hours of reperfusion. Post-surgery, triphenyltetrazolium chloride (TTC) staining was used to measure volume of cerebral infarction. EEG signals were continuously recorded throughout the procedure. We applied the Hilbert-Huang Transform (HHT) to analyze the EEG signals. HHT includes 2 steps: 1] empirical mode decomposition (EMD) to decompose the EEG signal into a set of intrinsic mode functions (IMFs); 2] the Hilbert Transform is applied to each IMF to compute analytic signals. Such analytic signals are represented in the complex plane, where they often form circular or elliptical contours (Fig. 1). The area of these contours in the complex plane contains unique information about variations in the signal properties. We computed the HHT area metric for the first four IMFs by using EEG recordings at 3 hours post-reperfusion (duration: 2 minute).Results and Conclusions:Our results showed the control group demonstrates higher correlations between the HHT area metric and the cerebral infarction size, compared to acute or chronic EMPA treatments (Fig. 2), with an especially significant correlation for IMF1in controls (R= -0.76). No significant difference was found in the HHT area metric between control, acute, and chronic EMPA (Fig. 3). It revealed that while EMPA treatments do not alter the EEG time-frequency features compared to controls, control group exhibits a stronger correlation between EEG features and cerebral infarction size. This indicates that EMPA’s neuroprotective effects might not be directly reflected in EEG changes, highlighting the need for further investigation of its mechanisms.

Stroke, Volume 56, Issue Suppl_1, Page ATP103-ATP103, February 1, 2025. Introduction:A visual arts-based intervention was developed and implemented for community-dwelling stroke survivors.Purpose:This study aimed to explore the participants’ experience of engaging in a visual arts-based intervention.Methods:Stroke survivors were recruited and randomly allocated to receive visual arts-based intervention or usual stroke care in the community settings. This intervention is a four-week group intervention with six activities guided by Bandura’ principles of self-efficacy, including warm-up activity, art-making activity, break, discussion, workbook review, and end-up activity. Semi-structured interviews were conducted with the participants after completing the intervention. Participants were invited to share their experience of engaging in the intervention, including comments, primary concerns, and difficulties encountered. Interview data were audio-recorded and transcribed as well as analyzed by thematic analysis.Results:Sixty-one participants (age range: 49 to 93) were interviewed. The results showed that most participants were satisfied with the intervention and appreciated the facilitator’s encouraging attitude. They appreciated the theme of each session, all of which enabled them to recall their memories to draw on meaningful values from their stroke recovery journey. Furthermore, over half of participants acknowledged that the intervention addressed their psychosocial concerns, which added values to address gaps in the traditional stroke rehabilitation. Specifically, they considered the creative approach in art-making activities and discussions enhanced their verbal and non-verbal expression, explored and expressed their inner emotions, and encouraged them to engage in group interactions. However, participation in the intervention was challenging for some participants. They pointed out some stroke-related barriers, such as blurred vision, slow reaction, lack of imagination, and limitation in hand movement, affecting their performances in group. Additionally, a lack of familiarity with art-making activity and tool for drawing also contributed to their difficulties in engaging in the intervention. To ensure the intervention implementation, participants suggested modifying the intervention to minimize barriers that hinder participants and establishing a more inclusive intervention environment in future.Conclusion:The qualitative results provided valuable insights of the impact of the visual arts-based intervention for stroke recovery.

Stroke, Volume 56, Issue Suppl_1, Page ATP150-ATP150, February 1, 2025. Introduction:Stroke is a significant global health challenge, impacting physical and mental well-being, with many neuropsychiatric symptoms contributing to worse functional outcomes. Post-stroke depression (PSD) is a common neuropsychiatric consequence of stroke, affecting approximately one third of stroke survivors. PSD is associated with worse functional outcomes, higher mortality rates, and reduced quality of life.Hypothesis:We hypothesize that patients with higher stroke severity scores on admission will have higher levels of immediate depressive symptoms and have a smaller household population.Methods:This study examines the predictive power of immediate post-stroke depressive symptoms and functional outcomes at 3- and 12- months post hospitalization. 130 patients with Ischemic stroke were enrolled and completed a standard battery of questionnaires during their hospitalization. Post-stroke depression was measured via PHQ-9 scores, with scores above 5 denoting moderate to severe depressive symptoms. Acute stroke severity was measured using the National Institute of Health Stroke Scale (NIHSS), with increasing scores indicating more severe strokes.Results:Analyzing stroke severity and PSD development among patients with ischemic stroke, our statistical analyses revealed that larger household size significantly protects against PSD. For acute stroke injury, we found that patients living with fewer people at baseline are more likely to have a higher NIHSS score (p

Stroke, Volume 56, Issue Suppl_1, Page ATMP94-ATMP94, February 1, 2025. Introduction:Previous single-center studies have found a higher prevalence of mental health disorders in parents of children with pediatric stroke compared to general population prevalences of 5% with depression and 6% with anxiety. Social determinants of health may influence mental health outcomes. We aimed to measure associations between social determinants of health and parental report of mental health symptoms following their child’s diagnosis of ischemic stroke.Methods:We performed a multicenter, international prospective study through the International Pediatric Stroke Study (IPSS). From 2016 to 2021, parents of children within 3.5 years after arterial ischemic stroke enrolled and completed validated and standardized surveys on anxiety (Beck’s Anxiety Inventory II), depression (Beck’s Depression Inventory), post-traumatic stress disorder (PTSD) (Post-Traumatic Stress Disorder Checklist for DSM-5), severity of their child’s stroke deficits (Recovery and Recurrence Questionnaire), and social determinants of health. For our statistical analysis we employed a linear mixed-effects model, both unadjusted and adjusted.Results:Fifty-two parents (13 fathers, 39 mothers) of 39 children enrolled. Of the 39 children 21 (54%) had perinatal stroke and 18 (46%) had childhood stroke. Median time from stroke diagnosis to parental survey completion was 1.3 years (interquartile range [IQR] 1.0-2.0). On parental surveys, parents scored in the clinical range for: depression in 35% of mothers and 23% of fathers; anxiety in 2% of mothers and 0% of fathers; PTSD in 26% of mothers and 8% of fathers. Lower parental education was significantly associated with higher levels of depression both in our unadjusted (0.02) and adjusted (0.03) models. Interestingly, the child’s functional outcome and parental income were not significantly associated with any parental mental health outcomes.Conclusion:Among social determinants of health, parental education level may be associated with depression in parents of children with pediatric arterial ischemic stroke and needs further exploration. Parents of children with pediatric arterial ischemic stroke had higher rates of depression and PTSD compared to general population estimates. Further research in this area will help facilitate understanding and development of interventions to prevent these mental health outcomes.

Stroke, Volume 56, Issue Suppl_1, Page ATP398-ATP398, February 1, 2025. Introduction:RNS60 is a proprietary 0.9% saline solution with an elevated oxygen concentration. Previously, we showed that 13 days of daily RNS60 treatment after transient middle cerebral artery occlusion (tMCAo) stroke reduced brain pathology (e.g., infarction, amyloid pathology, neuronal death, microglial activation, and white matter damage) while increasing microvascular perfusion and memory (Baena Caldas et al. 2024). Here, we examine earlier brain-protective effects of daily RNS60 treatment 4 days after stroke.Methods:Male C57BL/6J mice, 3-4 months old, were randomly divided into sham surgery or unilateral 60-minute tMCAo. Each group was subdivided into three treatment arms: an experimental arm receiving daily intraperitoneal injections of 0.2 mL of stabilized RNS60, and control arms of pressurized normal saline with the same oxygen content as RNS60 (PNS60) or normal saline (NS). Injections began 2 hours after stroke, once daily for 3 days. An additional group without treatment was used as a control. Treatment group assignments were blinded throughout the study. On day 4, mice from each group were euthanized to assess infarct volume using TTC staining, or were perfused with 4% PFA to perform immunohistochemistry.Results:Four days after ischemic stroke, daily injections of RNS60 treatment significantly reduced early post-stroke vasogenic edema by 41% and infarct size by 39% compared to controls. These RNS60 brain-protective effects were related to decreased expression of hypoxia-inducible factor 1α (HIF1α), suggesting that RNS60 treatment may reduce hypoxia.Conclusion:RNS60-treated mice exhibit early and long-term significant brain protection after ischemic stroke associated with decreased expression of HIF1α, suggesting reduced hypoxia in the ischemic brain. Ongoing studies aim to identify the effect of RNS60 on blood brain barrier integrity to further elucidate the underlying molecular mechanism.

Stroke, Volume 56, Issue Suppl_1, Page A23-A23, February 1, 2025. Background:Functional impairments following stroke remain a significant therapeutic challenge. Vivistim, FDA-approved since 2021, has shown consistent results, providing 2-3 more improvement in arm and hand function compared to intensive rehabilitation alone. At Atlantic Health System, 25 patients underwent Vivistim implantation and received Paired VNS rehabilitation.Methods:A multidisciplinary team at AHS identified, educated, and implanted Vivistim in 25 post-acute stroke patients with moderate-to-severe motor impairments in the arm and hand. Post-implantation, patients were referred to one of 11 sites. Regular follow-ups were conducted by the implanting team to monitor side effects, safety and efficacy of this novel intervention.Results:All 25 patients successfully underwent outpatient implantation, with no reported infections at the implant sites. One patient developed a hematoma that resolved without intervention. Another required device explantation approximately 410 days post-therapy due to tingling sensations near the implant site likely unrelated to the device. This patient maintained a 25-point improvement on the Fugl-Meyer Assessment-Upper Extremity (FMA-UE) despite explantation, indicating sustained benefits. Of the 25, 22 completed the therapy protocol. The remaining three discontinued therapy due to unrelated complications: one experienced two grand mal seizures linked to changes in seizure medication, another sustained an arm injury from a fall, and the third developed double vision, impairing her ability to drive. Patient ages ranged from 40 to 80 years (mean 62.6), with time to implantation post-stroke ranging from 1 to 11 years (mean 3.6). The interval from implantation to therapy initiation varied from 8 to 32 days (mean 15.3). The baseline FMA-UE score averaged 33 (range 19-56), with an average post-therapy score of 43 (range 24-63), for a mean improvement of 9.53 points. Notably, the patient with the longest follow-up (22 months) showed continued progress, reducing her 9-Hole Peg Test time by 61.42 seconds over her assessment 6 months prior.Conclusion:This case series represents the largest cohort reported to date from a single implanting site in a real-world setting. Vivistim was implanted safely, with no infections or surgical complications. Patients showed positive responses to Paired VNS despite an average of 3.6 years post-stroke, supporting the efficacy of this innovative treatment in the chronic stroke population.

Stroke, Volume 56, Issue Suppl_1, Page ATMP112-ATMP112, February 1, 2025. Introduction:Both histological and transcriptomic analyses of acute ischemic stroke (AIS) clots have identified features associated with mechanical thrombectomy (MT) outcome. However, few studies have explored how fluorescence histology and mRNA sequencing from the same clot can pinpoint specific biological phenomena associated with MT failure.Hypothesis:Joint analysis of paired clot immunofluorescence histology and mRNA sequencing will identify Neutrophil Extracellular Trap (NET) enrichment as a biomarker of MT first pass (FP) outcome.Methods:We performed paired histological and transcriptomic analysis of 32 stroke clots retrieved by MT (n=16 each of FP success and failure). Immunofluorescence histology was completed by co-staining 4µm clot tissue sections with antibodies against NET components (neutrophil elastase [ELANE], citrullinated histone [CitHis]) and super resolution imaging with instant structured illumination microscopy (ISIM) at 100X magnification. Differentially expressed genes (DEGs) were identified between transcriptomes of FP success and failure using the criteria of logFC≥1.5 and q

Stroke, Volume 56, Issue Suppl_1, Page ATP374-ATP374, February 1, 2025. Introduction:The cross-talk between the brain and peripheral immune organs plays a crucial role in the response to stroke injury. Spleen responses are implicated in stroke pathology and inflammatory responses. Hyperglycemia is known to worsen stroke outcomes, with increased immune cell infiltration into the brain. However, it remains unclear whether hyperglycemia exacerbates spleen immune cell responses and whether this contributes to the heightened immune response in hyperglycemic stroke.Method:Male C57/BL6 mice (10-12 weeks) were subjected to transient middle cerebral artery occlusion (MCAO) for 30 minutes, followed by reperfusion to mimic ischemic stroke. Acute hyperglycemia was induced by glucose injection 10 minutes before MCAO. The study included three groups: sham, MCAO only, and MCAO with hyperglycemia (n=6-7 per group). At 24 hours post-stroke, spleen and brain immune cell populations were analyzed using our established 12-color flow cytometry technique, which simultaneously analyzes myeloid and lymphoid subpopulations.Results:Compared with sham controls, stroke significantly decreased the numbers of dendritic cells (2.33 ± 0.48 vs. 1.50 ± 0.42 million; p

Stroke, Volume 56, Issue Suppl_1, Page ATP391-ATP391, February 1, 2025. Background:Calcitonin gene-related peptide (CGRP) is a potent vasodilator that plays a role in migraine. Monoclonal antibodies targeting CGRP, such as fremanezumab, is now widely used for migraine prevention. However, inhibition of CGRP system may also lead to vasoconstriction, raising concerns about whether the long-term treatment with these antibodies in migraine patients might increase the risk of stroke or worsen outcomes if a stroke occurs while taking these medications. Here, we aimed to investigate whether fremanezumab exacerbates stroke outcomes in a mouse model of ischemic stroke.Methods:Two middle cerebral artery occlusion (MCAO) models were used: a 12-minute occlusion simulating a transient ischemic attack (TIA) and a 60-minute occlusion representing a conventional stroke model. Fremanezumab was administered intraperitoneally at either 2 days or 7 days before MCAO induction in both models; one cohort received treatment 28 and 7 days before MCAO. On day 2 after reperfusion, brain tissues were harvested for TTC staining to evaluate infarct volume. Neurological function was assessed using a neuro score and corner test. Additionally, an angiogram using black ink was performed to visualize cerebral vasculature, and vessel diameters were measured to determine the impact of fremanezumab on vascular dimensions.Results:Angiographic arterial diameters in the fremanezumab arm did not differ from the saline arm, suggesting that fremanezumab does not cause vasoconstriction. In the TIA model, the fremanezumab group exhibited a trend towards increased infarct incidence and volume and hemorrhagic transformation, although these did not reach statistical significance. Additionally, there were no substantial changes in neurological scores and the corner test. In the 60-minute MCAO model, no significant changes or trends were observed in infarct volume or other outcomes between the two treatment arms. Outcomes were similar when fremanezumab was administered 2 or 7 days before MCAO.Conclusion:Despite previous concerns that long-term use of fremanezumab might exacerbate stroke risk by promoting vasoconstriction, our findings do not support this hypothesis and suggest that fremanezumab does not worsen stroke outcomes in these models. These findings have important implications for the management of stroke risk in patients using fremanezumab for migraine prevention, suggesting that it may be used with confidence regarding its impact on stroke risk.

Stroke, Volume 56, Issue Suppl_1, Page A14-A14, February 1, 2025. Funding:The INSIGHT Registry is funded by Penumbra.Introduction:Rapid and precise determination of the etiology of acute ischemic stroke is crucial in long-term management and prevention of recurrence. Identification of etiology-associated molecular biomarkers following thrombectomy may allow for personalized intervention. Here, we examine the transcriptomics of cardioembolic thrombi as a result of atrial fibrillation, identifying a distinct transcriptomic signature relative to other causes of ischemic stroke.Methods:The INSIGHT registry is a prospective, multicenter, multi-omic registry focused on elucidating the molecular underpinnings of stroke from analysis of clot and interarterial blood. RNA sequencing of 10,990 genes from 292 thrombi from patients undergoing thrombectomy was analyzed using edgeR, sva, and limma/voom. 111 patients had a determined etiology of atrial fibrillation. Controls had unknown, atheroembolic, or coagulopathy stroke etiology. Significant association of thrombus gene expression with atrial fibrillation was conducted using the Wilcoxon Rank Sum test using Benjamini-Hochberg multiple testing correction (FDR

Stroke, Volume 56, Issue Suppl_1, Page ATP399-ATP399, February 1, 2025. After ischemic stroke (IS), the cytotoxic T (Cyto T) cells infusing to the infarct site enhance the neuroinflammation. Previous studies have shown that increasing the proportion of regulatory T (Treg) cells relative to Cyto T cells can alleviate inflammatory conditions. Poly-Glu/Tyr polypeptide (Poly-YE; P-YE) was reported as a one of the key immune modulators to just modulate T cell balance. Therefore, we focused on screening target protein that affect T cell balance by P-YE. To screen target protein, we carried out protein microarray and showed that P-YE strongly bound to neutrophil cytosolic factor (NCF1) which is a one part of NOX complex. In the inflammatory response, activated NCF1 is known to bind to Moesin (MSN) to migrate forward to the membrane and assemble into the NOX complex. Also, recent study showed that unbound MSN to NCF1 induces FOXP3 expression in helper T cells. Based on this data, we hypothesized that ‘NCF1+ P-YE’ binding leads to the inhibition of NOX complex assembly and the conversion of Cyto T cells to Treg cells in neuroinflammation. P-YE loaded on Nanoparticles (Np P-YE; 3ug/mL) was treated to primary Cyto T (CD8+ T) cell isolated from the spleen of 8-week-old C57BL/6 male mouse. These cells were cultured in Oxygen-Glucose Deprivation-conditioned microglia medium (OGD-conditioned medium; CM) to mimic exposure to neuroinflammation. The results showed that Np P-YE fused to the cell membrane and entered to cytosol of CD8+ T cell. In the CM group treated with P-YE, superoxide was remarkably decreased and CD8+ T cells expressed FOXP3. In Co-IP, we confirmed that the binding of NCF1 and P-YE liberated MSN. Also, Proteome cytokine array showed that P-YE treatment group reduced cytokines compared with non-treatment group. In tMCAO modeling mice injected with P-YE (1mg/kg), the infarct area decreased and the pro-inflammatory phenotype of microglia was reduced. Finally, through behavior tests, the mice injected P-YE after tMCAO surgery showed improvement in stereotyped behavior and weakness due to ischemic damage. Taken together, NCF1 bound to P-YE can’t form NOX complex and MSN dissociated from NCF1 may lead to FOXP3 expression. Therefore, P-YE binds to NCF1 under neuroinflammatory conditions, converting some CD8+ T cells into CD8+FOXP3+ cells, thereby inhibiting ROS production and exerting anti-inflammatory effects.