Risultati per: Linee Guida per le cure post-parto

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.

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.

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.

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

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.

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.

Stroke, Volume 56, Issue Suppl_1, Page ATP284-ATP284, February 1, 2025. Enrichment is the prospective use of any patient characteristic to select a study population at higher risk in which detection of a drug effect is more likely than it would be in an unselected population. Patients with post-stroke cognitive impairment (PSCI) found to have higher risk of stroke recurrence in a recently completed meta-analysis. The goal of this study is to test whether PSCI based patient selection may represent enrichment strategy for secondary stroke prevention clinical trial. This is a subgroup analysis of Insulin Resistance Intervention after Stroke (IRIS) trial. In IRIS trial, patients were randomized to receive pioglitazone vs. placebo and had a baseline Modified Mini-Mental State Examination (3MS, where 3MS ≤ 88 was indicative of global PSCI. The primary endpoint of the study was recurrent stroke or MI. We estimated the hazard ratio (HR) for the effect of pioglitazone among those with global PSCI. To determine the sample size for a subsequent trial enriched by including only subjects with global PSCI, we make the following assumptions: (1) time to event follows an exponential distribution in both the pioglizone and placebo groups where the hazard rate for the placebo group is assumed to be the same as in the IRIS trial among those with global PSCI; (2) hazards for the pioglitizon and placebo groups are proportional over the course of the study; and (3) subjects are randomized to pioglitazone or placebo in equal proportions.Data on n = 3,338 patients of original cohort of n = 3,876 were analyzed, and n = 473 among them had PSCI at baseline. During 5-years of follow-up, n=246 patients experienced recurrent stroke, and n = 118 had MI. In patients with PSCI HR was 0.56 (95% CI 0.34 – 0.92) suggesting a 44% reduction in the hazard rate for secondary stroke or MI after 5 years of follow-up in the pioglitizone group compared to the placebo. If we conservatively assume that the true HR = 0.56 (closer to the null of HR = 1 than what was observed in the IRIS trial), then a total sample size of n= 967 willl proivde 90% power using a two-sided log-rank test at the 5% significance level. This conservative sample size corresponds to a 75% reduction in the sample size that was required for the IRIS Trial. PSCI screening may represent enrichment strategy for secondary stroke prevention clinical trial potentially reducing sample size by 75%. PSCI screening-based enrichment can be tested in phase 2 secondary stroke prevention trial.

Stroke, Volume 56, Issue Suppl_1, Page AWP294-AWP294, February 1, 2025. Background:Racial disparities have been well described in cardiovascular disease. However, the impact of race on the risk of stroke among infective endocarditis (IE) patients is not well understood.Objective:This study aims to investigate the racial disparities in the risk of stroke and clinical outcomes among IE patients.Method:The TriNeTX Global Collaborative Network database was used to identify patients aged ≥18 years of age from January 2000 to May 2023 which included IE patients. Patients were categorized into two groups, one with Black or African American and another with White race patients. Both groups were followed for 12 months. Propensity score-matched analysis (PSM) (1:1) was performed on age, gender, BMI, hypertension, diabetes mellitus, chronic kidney disease, hemoglobin level, LDL level, left ventricular ejection fraction and various drugs including beta blockers, ACEi and ARBi. Primary outcome was ischemic stroke, while secondary outcomes were all-cause mortality, heart failure, cardiogenic shock, MACE (composite of all-cause mortality, heart failure, and ischemic stroke), and acute kidney injury (AKI).Result:After 1:1 propensity score matching, the study cohort comprised 9, 814 Black patients and 9, 814 White patients. The mean age of patients was comparable between both groups (59.8 and 63.1 years). IE patients were having a comparable risk of ischemic stroke among both the races after 1 month (RR, 1.17 (95% CI: 0.96-1.42), P = 0.11), however, the risk of ischemic stroke was significantly higher among Black patients after 1 year (RR, 1.18 (95% CI:1.02-1.36), P = 0.024) when compared with White patients. Black patients were having a significantly higher risk of all-cause mortality after one month (RR, 0.818 (95% CI: 0.74-0.89), P

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.

Stroke, Volume 56, Issue Suppl_1, Page ADP26-ADP26, February 1, 2025. Introduction:Short interspersed nuclear elements (SINEs) are an abundant class of noncoding retrotransposons that can be transcribed by RNA polymerase III. Some SINEs have also been shown to act as genomic enhancers, thus giving rise to what are known as enhancer SINE-RNAs (eSINE-RNAs). The function of these novel RNAs within the post-stroke brain remains virtually unexplored. In this study, we map the genome-wide cortical expression of eSINE-RNAs in response to stroke, characterize their cell-type&subcellular localization, and determine their role in affecting post-stroke infarct volumes.Methods:Ischemic stroke was induced in male C57BL/6N mice using 1h middle cerebral artery occlusion (MCAO) followed by 6h of reperfusion (or sham surgery). Genome-wide RNA-seq and H3K27ac ChIP-seq (n=3/group/experiment) were performed on ipsilateral cortices to identify stroke-responsive enhancer RNA transcripts, which were then overlaid with genomic SINEs to identify eSINE-RNAs. Immunohistochemistry and RNA-FISH were used in tandem to determine the cell-type and subcellular localization of several highly expressed eSINE-RNAs. Select eSINE-RNAs were ablated via intracerebroventricular injection of antisense oligonucleotides followed by 1h MCAO and 24h reperfusion. Infarct volumes following knockdown were evaluated using cresyl violet staining (n=5-7/group).Results:We discovered 46 eSINE-RNAs upregulated in the cortex following MCAO, 33 of which were unique to stroke and not detected in the sham group. These RNAs were derived from several families of SINEs, including 24 from the B1 family, 20 from the B2 family, and one each from the less ubiquitous ID and MIR families. The expression of several abundant eSINE-RNAs was specific to the nuclei of neurons within the prospective infarct and peri-infarct territories, including the sensorimotor cortex and hippocampus. Ablation of select eSINE-RNAs resulted in significantly higher infarct volumes versus controls, suggesting that these eSINE-RNAs serve a neuroprotective role in the brain following ischemic stroke.Conclusion:Our study is the first report to characterize the expression of eSINE-RNAs in the post-stroke brain and begin to elucidate their function as regulators of post-stroke pathophysiology. Our results suggest that the transcription of eSINE-RNAs represents a robust neuroprotective response to transient focal ischemia, thus positioning them as potential molecular targets for modulating post-stroke outcomes.

Stroke, Volume 56, Issue Suppl_1, Page ADP56-ADP56, February 1, 2025. Introduction:We discovered a marked upregulation of MMP-12 levels in the brain following an ischemic stroke and demonstrated that reducing MMP-12 levels in otherwise healthy rodents decreases brain damage and facilitates functional recovery. This study aimed to assess the effectiveness of MMP-12 gene silencing in improving sensorimotor function recovery in aged mice and hypertensive rats.Methods:Both male and female C57BL/6 mice (≥16 months old) and male spontaneously hypertensive rats (SHRs) (2-3 months old) were subjected to 35-min and 1-h transient right middle cerebral artery occlusion (MCAO), respectively. Appropriate cohorts of animals (25 mice/group; 18 rats/group) received either control shRNA or MMP-12 shRNA plasmids (1 mg/kg) formulated as nanoparticles that were administered intravenously via tail vein 2 h after reperfusion. In mice, stroke symptoms were evaluated using the neurological deficit score at 2-4 hours and 1 day after reperfusion, while the modified neurological severity score was used in rats. Sensorimotor functions were assessed using the sticky tape test, pole test, and rotarod test at baseline (before MCAO) and at regular intervals post-MCAO (days 3, 5, and 7 in mice, and days 1, 3, 5, 7, and 14 in rats).Results:MMP-12 expression in the ischemic brain was significantly increased by 35-min MCAO in aged mice and 1-h MCAO in SHRs, as was previously observed in healthy young mice and rats that were subjected to 1-h and 2-h MCAO, respectively. In comparison to the control shRNA treatment, MMP-12 shRNA treatment facilitated a greater mean recovery of somatosensory function in aged mice (sticky tape latency was significant on day 3 and day 5; sticky tape interaction was significant on day 5) and in SHRs (sticky tape ratio was significant on day 14). Furthermore, MMP-12 shRNA treatment resulted in a greater mean recovery of motor function across all tested time points in aged mice (pole descent score was significant on day 7; rotarod latency was significant on day 7) and in SHRs (rotarod latency was significant on day 5 and day 14).Conclusions:Reducing MMP-12 expression in the ischemic brain facilitates the recovery of both somatosensory and motor function in aged mice and hypertensive rats after transient focal cerebral ischemia. Our findings further reinforce the potential benefits of MMP-12 gene silencing as a therapeutic approach for improving recovery outcomes in stroke patients.

Stroke, Volume 56, Issue Suppl_1, Page ATP1-ATP1, February 1, 2025. Background and Objective:The effect of time from onset to treatment on reperfusion in an extended time window remains unexplored. This study aimed to investigate the relationship between the time to treatment and the probability of reperfusion in acute ischemic stroke patients with large vessel occlusion treated with tenecteplase in an extended time window, using data from the Chinese Acute tissue-Based imaging selection for Lysis In Stroke Tenecteplase (CHABLIS-T) trials.Methods:This study included patients treated with intravenous tenecteplase from the CHABLIS-T1 and CHABLIS-T2 clinical trials, both of which screened patients in the extended window using CT perfusion (CTP) imaging. Major reperfusion was assessed through follow-up CTP or digital subtraction angiography (DSA) imaging. Time variables, including the time from last known normal (LKN) /symptom onset to hospital arrival/ administration of tenecteplase were entered as continuous, categorical, and cubic spline variables in multivariable logistic regression models to explore their association with the probability of post-thrombolytic reperfusion.Results:A total of 199 patients arrived within 4.5-24 hours from LKN were included in this study, of whom 67 achieved post-thrombolytic major reperfusion. Cubic spline analysis indicated a linear correlation between time variables and the probability of reperfusion. Therefore, time variables were entered as continuous or categorical variables in the regression models. Multivariable logistic regression analysis revealed that a longer time from LKN to hospital arrival was associated with a lower probability of major reperfusion (continuous variable: OR=0.998, P=0.018,Figure 1). Similarly, a longer time from LKN to thrombolysis was associated with a lower probability of reperfusion (continuous variable: OR=0.996, P=0.020,Figure 2; categorical variable: OR=0.043, P=0.005,Figure 3). The analysis of time from symptom onset to hospital arrival/thrombolysis and reperfusion drew similar resultsConclusion:In acute ischemic stroke patients with large vessel occlusion treated with tenecteplase in an extended time window, a longer time to treatment was associated with a lower probability of post-thrombolytic reperfusion. Therefore, rapid reperfusion treatment should still be required even in patients with large vessel occlusion in an extended time window with a good collateral flow, in order to optimize treatment effect.

Stroke, Volume 56, Issue Suppl_1, Page A114-A114, February 1, 2025. Introduction:Post-stroke neuroinflammation is a hallmark of ischemic stroke. This study investigates the role of IGSF6 in microglia during ischemic stroke and its contribution to neuroinflammatory responses and brain injury following stroke.Methods:IGSF6 expression was examined in murine microglia under various inflammatory stimuli. Using a middle cerebral artery occlusion (MCAO) model, we evaluated the impact of microglialIgsf6knockdown (Igsf6-KD) on neuroinflammation and ischemic outcomes. Pro-inflammatory cytokine levels were measured using qPCR and ELISA in bothIgsf6-KD and wild-type (WT) mice, and functional outcomes were assessed through neurological tests. Subcellular localization and cytokine trafficking studies were conducted using immunofluorescence, electron microscopy, and protein interaction assays.Results:IGSF6 expression was significantly upregulated in microglia following MCAO. Knockdown of Igsf6 in microglia resulted in reduced secretion of pro-inflammatory cytokines (TNF, IL-6, CCL2, CCL5) at day 1 post-stroke, despite unchanged mRNA levels. Morphological analysis of microglia fromIgsf6-KD mice revealed a less reactive phenotype. Additionally,Igsf6-KD mice exhibited a reduction in infarct volume and improved functional outcomes, including enhanced performance on rotarod, grip strength, and foot-fault tests.Mechanistically, IGSF6 was shown to localize to the trans-Golgi network (TGN) and mediate cytokine trafficking. Knockdown ofIgsf6disrupted this process, reducing the secretion of key cytokines without affecting their transcription or translation.Conclusions:Microglial IGSF6 exacerbates post-stroke neuroinflammation by promoting the secretion of pro-inflammatory cytokines. Its knockdown attenuates neuroinflammatory responses, reduces ischemic brain injury, and improves functional recovery. These findings highlight the detrimental role of IGSF6 in stroke pathology and suggest that targeting IGSF6 may offer therapeutic benefits for mitigating neuroinflammation and improving outcomes after ischemic stroke.

Stroke, Volume 56, Issue Suppl_1, Page ADP31-ADP31, February 1, 2025. Introduction:CT perfusion maps (CTP) can estimate the ischemic core in acute ischemic stroke based on distinctive cerebral blood flow (CBF) thresholds. However, metabolic factors beyond perfusion influence the tissue tolerance to ischemia and the infarct growth rate.Hypothesis:We hypothesize that patients with lower hemoglobin and higher blood glucose levels exhibit reduced cerebral tissue resilience to hypoperfusion and will show larger ischemic core underestimation volume (ICuV) compared to other patients with normal hemoglobin and blood glucose levels.Methods:Large vessel occlusion stroke patients investigated with baseline CTP undergoing thrombectomy with near-complete reperfusion and without parenchymal hemorrhage from the ESCAPE-NA1 trial were included. Patients were subdivided into anemic (Hgb

Stroke, Volume 56, Issue Suppl_1, Page ATP264-ATP264, February 1, 2025. Introduction:Children with cardiac diseases are at an increased risk to develop ischemic stroke that can lead to lifelong neurological deficits. Blood pressure is an important modifiable factor associated with poor neurological outcomes. However, there lacks sufficient evidence to provide patient specific blood pressure guidelines post pediatric ischemic stroke.Objective:We evaluated blood pressure mean and changes in pediatric patients with cardiac diseases within the first 48hours cardiac critical care unit (CCCU) after an arterial ischemic stroke.Method:We conducted a retrospective study of children diagnosed with acute arterial ischemic stroke admitted to the CCCU. We reviewed data on demographics, clinical outcome, radiologic, hemodynamic parameters, and medication. Ischemic lesion volume size was obtained from Diffusion-Weighted Imaging by a full-trained neuroradiologist. Blood pressure percentile was obtained based on age, sex, and the 50thheight range. We contrasted the blood pressure with age and admission year matched CCCU controls without a history of stroke. We used linear regression to model blood pressure trends, t-test to compare continuous data, and chi square analyses to compare discrete data points.Results:Twenty-nine stroke patients (34% female, median age 2.1 years and range 17 years) were included. The majority of patients aged up to 3 years-old, presented with congenital heart defects (69%). Older patients presented more often with acquired heart disease (40%). Blood pressure means and trends differed by age, cardiac disease, and neurological outcomes. Younger patients and those with congenital heart defects had higher blood pressure compared to controls. Older patients or those with acquired heart diseases tended to have lower systolic blood pressure and higher diastolic blood pressure than their control. A third of patients with neurological deficits presented with an average blood pressure greater than the 95thpercentile, while patients with normal neurological status at discharge all had an average blood pressure inferior to the 50thpercentile. Higher blood pressure was associated with worst neurological outcomes, and larger ischemic brain volume size.Conclusion:Patients with cardiac disease have age and cardiac anomaly specific blood pressure after an acute ischemic stroke. Further research into these differences and blood pressure management in this group is crucial to lessening the burden of stroke on this at risk population.

Stroke, Volume 56, Issue Suppl_1, Page ATP263-ATP263, February 1, 2025. Introduction:Children with arteriopathy are at an increased risk to develop ischemic stroke that can lead to lifelong neurological deficits. Blood pressure is an important modifiable factor associated with poor neurological outcomes. However, there is a lack of sufficient evidence to provide patient specific blood pressure guidelines post pediatric ischemic stroke.Objective:We aimed to evaluate blood pressure averages and changes in pediatric patients with arteriopathy within the first 48 hours in intensive care after an arterial ischemic stroke.Method:We conducted a retrospective study of children diagnosed with acute arterial ischemic stroke admitted to the pediatric intensive care unit (PICU). We reviewed data on demographics, clinical outcome, radiologic, hemodynamic signs, and medication within PICU. Ischemic lesion volume size was obtained from Diffusion-Weighted Imaging by a full-trained neuroradiologist. Blood pressure percentile was obtained based on age, sex, and the 50thheight rang. We also contrasted blood pressures of stroke patients with age and admission year matched controls without a history of stroke. We used linear regression to model blood pressure trends, t-test to compare continuous data, and chi square analyses to compare discrete data points.Results:Forty-five patients (49% female, median age 7.8 years, range age 17 years) were included. Arteriopathy disease included Dissection, Moyamoya, Focal Cerebral Arteriopathy and Vasculitis. Despite only a minority of patients being on vasoactive medications, patients with arteriopathy had higher blood pressures compared to age-matched control PICU patients in the first 48 hours. In addition, 31% of arteriopathy patients had an average systolic blood pressure greater than the 95thpercentile for the first two days after an acute arterial ischemic stroke, versus only 14% of their control (p-value < 0.05). Neurological deficits and increased brain ischemic lesion volume were associated with higher blood pressures.Conclusion:Understanding blood pressure trends and outcomes after an ischemic stroke in children at risk is crucial to guide the management of this modifiable factor. Blood pressure in children with arteriopathy is increased after an ischemic stroke compared to controls admitted to PICU. Further research into the etiology of differences observed here and blood pressure management is crucial to reducing the burden of pediatric ischemic stroke on this at risk population.