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Stroke, Volume 56, Issue Suppl_1, Page AWP349-AWP349, February 1, 2025. The first Stroke Preclinical Assessment Network (SPAN 1) tested 6 therapeutic interventions initiated at the time of reperfusion in models of focal ischemic stroke, including models of cardiovascular risk factors. To improve preclinical testing rigor and reproducibility, the testing was conducted as a large, randomized controlled trial across 6 sites with a coordinating center that concealed treatments and blinded neurobehavior video assessments. The trial had an adaptive design with preset levels of efficacy and futility interrogated after each of 4 stages relative to placebo (P). The primary outcome was turning preference on the corner test at 30 days. Secondary outcomes included corner test turns at 7 days, foot-faults on a grid walk test at 7 and 30 days, and MRI lesion volume at 2 and atrophy at 30 days. Based on the primary outcome data pooled from young mice, aging mice, high-fat diet obese mice and spontaneously hypertensive rats (SHRs), the poly(ADP-ribose) polymerase (PARP) inhibitor, veliparib (V), was considered futile after the second stage (V=271; P=171). Here, we performed a secondary analysis of the veliparib data on individual subgroup models, secondary outcomes, and effects of sex. Veliparib (10 mg/kg) injected IV at reperfusion failed to show a benefit on the corner test or grid walk test at 7 or 30 days of recovery or a reduction in lesion volume in young mice (V=114; P=56), obese mice (V=38; P=34), or SHRs (V=39; P=41). However, in aging mice (17-18-months-old; V=39; P=40), veliparib significantly improved performance on the corner test (P= 0.009) and grid walk test (P= 0.002) at 7 days; the benefit was independent of sex. However, mortality in the aging mice was greater than in the other subgroup models at all sites, and significance in the corner test was lost at 30 days (P= 0.10) associated with the decreased sample size. Aging mice were especially susceptible to respiratory arrest during anesthesia while conducting MRI scans. Lesion volume at 2 days was small in the veliparib (2-3% of hemisphere) and placebo (4%) groups, suggesting that the benefit of veliparib on neurobehavior might be due to its known anti-inflammatory effects rather than by decreasing infarct volume. Because ischemic stroke predominantly occurs in the aging population, further research into the neurobehavior benefit of PARP inhibitors in aged animal models of stroke is warranted in protocols that omit post-ischemic anesthesia so as to improve survival.

Stroke, Volume 56, Issue Suppl_1, Page AWP342-AWP342, February 1, 2025. Background:Elevated circulating IL-6 levels are associated with poor outcomes following stroke, and increased serum IL-6 levels correlate with worse stroke outcomes. IL-6 binds to soluble IL-6 receptors, binding to ubiquitously expressed gp130 to initiate proinflammatory trans-signaling. This exploratory study investigates the impact of inhibiting IL-6 trans-signaling on long-term functional outcomes in ischemic stroke.Methods:Young mice (8-15 weeks old) were administered recombinant saline/gp130Fc an IL-6 trans-signaling inhibitor, twice a week for two weeks, starting at the time of reperfusion after 60 minutes of post-middle cerebral artery occlusion (MCAO). Neurological deficit scores and infarct volumes were assessed at 24 hours, with long-term cognitive and motor evaluations conducted at 7 and 28 days post-MCAO. Gliosis and neurogenesis were analyzed via fluorescence microscopy, and plasma IL-6 levels were quantified using ELISA. Flow cytometry was performed to assess membrane IL-6 receptor and IL-6 levels on immune cells in the blood and brain at 24,72 hours and 7 days post-MCAO.Results:MCAO in young male mice significantly increased IL-6 expression while acutely reducing membrane IL-6 receptor levels in peripheral immune cells. Treatment with gp130Fc (0.5 mg/kg) effectively improved neurological deficit scores (NDS) and reduced infarct volume (p

Stroke, Volume 56, Issue Suppl_1, Page AWP344-AWP344, February 1, 2025. Introduction:Nitro-oleic acid (OA-NO2) is an endogenous peroxisome proliferator-activated receptor-γ (PPARγ) ligand and can activate this receptor under both physiological and pathological conditions. In this study, we explore the role and molecular mechanisms of OA-NO2in maintaining blood-brain barrier (BBB) integrity and enhancing neurovascular function during ischemic stroke, with a particular emphasis on the activation of PPARγ signaling pathways.Methods:EC-selective PPARγ conditional knockout (EC-PPARγ cKO) and wild-type (WT) mice underwent 1-hour middle cerebral artery occlusion (MCAO) with 1 to 7 days of reperfusion. Mice were treated with oleic acid (OA) or OA-NO2(10 mg/kg) via tail vein 2 hours after MCAO. Sensorimotor function was assessed using the rotarod, foot fault, and adhesive tape removal tests. BBB integrity was measured with fluorescein-dextrans, and brain infarct was analyzed with anti-MAP2 immunostaining. Peripheral immune cell infiltration was examined by immunofluorescent methods. Total RNA and proteins were extracted from brain tissue. BBB tight junction mRNAs, proteins, and inflammatory factors were quantified using qPCR and Western blotting.Results:OA-NO2treatment significantly enhanced sensorimotor function in stroke mice compared to the OA group. However, this beneficial effect was lost in the EC-PPARγ cKO mice. Compared to OA controls, intravenous administration of OA-NO2led to reduced BBB leakage in ischemic brains, as indicated by a significant decrease in the extravasation of BBB tracers. This reduction in BBB leakage was also abolished in the EC-PPARγ cKO mice. Furthermore, OA-NO2treatment reduced brain infarction in stroke mice, but this protective effect was completely reversed in the EC-PPARγ cKO mice. Interestingly, OA-NO2treatment promoted a shift towards an anti-inflammatory microglial phenotype (M2) in the peri-infarct regions of EC-PPARγ WT mice, but not in EC-PPARγ cKO mice. Mechanistically, OA-NO2increased levels of major endothelial tight junction mRNAs and proteins, including Claudin 5 and ZO-1, in EC-PPARγ WT mice but not in EC-PPARγ cKO mice following ischemic stroke.Conclusions:Treatment with OA-NO2effectively reduces BBB leakage-triggered peripheral immune cell infiltration, brain infarction, and long-term neurobehavioral deficits in mice following ischemic stroke. The neurovascular protection conferred by OA-NO2primarily operates through PPARγ-dependent signaling pathways.

Stroke, Volume 56, Issue Suppl_1, Page AWP114-AWP114, February 1, 2025. Introduction:Two-thirds of US stroke patients undergo rehabilitation post-discharge with about 20% and 25% receiving care at an inpatient rehabilitation facility (IRF) and skilled nursing facility (SNF), respectively. Total rehabilitation time for stroke patients discharged to SNF are about twice as long as those of IRF, but the effect of hospital readmission (to acute care) on the continuity of rehabilitation care in either setting is not known.Methods:We probabilistically linked data from Michigan’s Coverdell Stroke Program and Michigan Value Collaborative claims database for Medicare FFS beneficiaries following acute stroke (ICD-10 I61-I63) between 2016-2020. Patients admitted to IRF or SNF after hospital discharge were confirmed using claims data. We followed patients for 30 days post-discharge and compared the all-cause readmission rate, initial rehabilitation length of stay, 30-day total rehabilitation length of stay (in the same setting), and number of admissions to the same rehabilitation setting between IRF and SNF patients.Results:From an initial cohort of 14,316 patients, we identified 2,995 (20.9%) and 2,948 (20.6%) directly admitted to IRF or SNF following stroke hospitalization, respectively. Compared to SNF patients, IRF patients were younger, and more likely to be male, have minor strokes (NIHSS 1-4), and be able to ambulate at hospital discharge. Over 30 days of follow up, 12.6% (n=376) of IRF and 19.6% (n=577) of SNF patients were readmitted at least once to an acute hospital setting (Table). Of the patients who experienced readmission, SNF patients were more likely to be readmitted to a SNF rehabilitation setting compared to IRF patients being readmitted to an IRF setting (mean number of SNF admissions = 2.1 vs mean number of IRF admissions = 1.3). The mean length of stay of the initial IRF and SNF care settings were 14.6 (SD=8.0) and 11.5 (SD=8.2) days, respectively. However, the mean cumulative length of stay in the same rehabilitation setting over the 30-day period increased slightly to 15.3 (SD=8.1) days for IRF patients but increased substantially to 26.4 (SD=21.3) days for SNF patients.Conclusions:Readmission to the acute hospital has a disrupting effect on the continuity of rehabilitation care especially for SNF patients who are less likely to complete their initial rehabilitation stay. However, because most SNF patients return to SNF, the cumulative amount of rehabilitation care is close to the theoretical 30 day maximum.

Stroke, Volume 56, Issue Suppl_1, Page AWP111-AWP111, February 1, 2025. Introduction:Few treatments have been shown to be efficacious for the 75% of individuals who have persistent moderate to severe upper extremity (UE) hemiparesis. Bilateral upper limb motor priming (BUMP) combined with upper limb therapy presents a potential practical solution to maximize recovery across a range of upper limb impairment levels. BUMP is a repetitive sensorimotor intervention which affects brain excitability by using mirror bilateral, wrist movements via a device with a mechanical linkage so the less affected and affected hands move symmetrically. We aimed to assess the magnitude of change in arm function in people with moderate-to-severe UL hemiparesis undergoing 30 hours of BUMP + task-specific training (TST), compared to a group receiving 30 hours of control priming (CP) + TST. Here we present the results of the BUMP trial.Methods:Seventy-six participants with moderate to severe hemiparesis, ≥6 months post stroke, were stratified by baseline impairment and randomized using 2 computer-generated number lists to receive BUMP or CP prior to receiving the same TST protocol. Over 6 weeks, participants received 30 hours of BUMP + TST or CP (defined as sham electrical stimulation) + TST. The primary outcome was the change in Fugl Meyer Assessment Upper Extremity (FMA-UE) score from baseline to follow up, 8 weeks after treatment ended. Outcome assessors were masked to group assignment. Analyses were intention to treat. We also report clinically meaningful response rates defined as a change in FMA-UE score of 6 points or greater.Results:Participants were randomized to either BUMP (N=37) or CP+TST (N=36). One person was withdrawn from the BUMP group and 2 people from the CP group. At follow up (8 weeks post-treatment end), both groups showed significant improvement in the FMA-UE. Those in BUMP and CP saw a mean change of 5.68 (SE 0.76, p

Stroke, Volume 56, Issue Suppl_1, Page AWMP97-AWMP97, February 1, 2025. Background:The advancement of age is associated with an increased incidence of both cerebral small vessel disease (CSVD) and sleep disorders, which are recognized as risk factors for cognitive decline. Recent studies suggest that the glymphatic system may play an important role in these relationships.Methods:In this cross-sectional and longitudinal study, participants from Shanghai Aging Study underwent multi-modal MRI, Pittsburgh Sleep Quality Index (PSQI) and neuropsychological assessment. Diffusion tensor image analysis along the perivascular space (DTI-ALPS) index was employed to evaluate the function of glymphatic system. Spearman correlation and partial correlation analyses were used to explore the relationships between CSVD burden/sleep disorders, glymphatic dysfunction, and cognition. Furthermore, mediation analysis was conducted to investigate the potential mediating effects of DTI-ALPS in the association between CSVD/PSQI and cognition. We further examined the interaction effects between CSVD burden and sleep disorders on cognitive outcomes.Results:258 participants were included in this study (average age, 68.5 years), among which 133 participants were followed up after a 7-year interval. At baseline, DTI-ALPS was significantly correlated with PSQI (r = -0.174, p = 0.005) and various imaging biomarkers of CSVD after adjusting for age, gender, vascular risk factors, and ApoE4. Additionally, DTI-ALPS was significantly correlated with executive function (r = -0.237, p < 0.001), memory (r = 0.146, p = 0.02), and visuospatial ability (r = 0.154, p = 0.014). Mediation analysis indicated that DTI-ALPS simultaneously mediated the association between CSVD burden/sleep disorders and cognitive decline, with a complete mediation effect of 19.22% between CSVD burden and executive function, 13.03% between PSQI and memory. Interaction analysis showed that the impacts of sleep disorders on general cognitive function and executive function were more significant among older adults at high risk of CSVD. Longitudinally, classic imaging biomarkers of CSVD as well as DTI-ALPS were significantly related to long-term changes in cognition.Conclusion:The study reveals that glymphatic dysfunction serves as a link to closely connect sleep disorders/CSVD with cognitive decline in community-dwelling older adults. Moreover, the interaction effect between two risk factors emphasizes the importance of individualized sleep management in the elderly at high risk of CSVD.

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 AWP134-AWP134, February 1, 2025. Introduction:Stroke is a leading cause of maternal morbidity and mortality, and hemorrhagic strokes account for up to half of these cases. Prior studies in non-maternal populations demonstrated that 9% of strokes are missed at initial ED presentation. We hypothesized that pregnant or postpartum patients with acute hemorrhagic stroke would have higher odds of delayed or missed diagnosis at the time of their initial presentation, compared with those with thrombotic strokes (arterial ischemic stroke [AIS] or cerebral venous thrombosis [CVT]).Methods:We retrospectively identified female patients aged 18-50 years treated at 5 stroke centers between 1/1/2012 and 12/31/2021 with a confirmed diagnosis of AIS, intracerebral hemorrhage (ICH), subarachnoid hemorrhage (SAH) or CVT. Patients who were pregnant or within 1 year of delivery at the time of stroke underwent medical chart review by vascular neurologists at each center. Medical encounters leading up to the stroke diagnosis were evaluated using the Safer Stroke-Dx instrument, a validated chart review tool to identify encounters with a missed opportunity to diagnose stroke. Encounters were categorized as “diagnostic delay” or “no diagnostic delay.” Patients with insufficient data for a determination were categorized as “no diagnostic delay.”Results:A total of 121 patients were identified, of whom 48% had hemorrhagic stroke. Overall, 29% of patients experienced diagnostic delays. Age and vascular risk factors did not differ significantly between those with diagnostic delays and those without (Table). More patients in the group with diagnostic delays were Black (49% vs 31%) or Hispanic (23% vs 12%). The proportions of stroke subtype for diagnostic delays and no diagnostic delays are shown in theFigure. The odds of diagnostic delays were higher for individuals with hemorrhagic stroke compared to those with thrombotic strokes (OR 2.35, 95% CI 1.05-5.28). Adjusting for race and ethnicity did not change the effect.Conclusions:The odds of experiencing a diagnostic delay were more than doubled for pregnant and postpartum patients with hemorrhagic strokes compared to those with thrombotic strokes. More research is needed to identify contributing factors to diagnostic delays in maternal stroke, and to develop tailored stroke screening tools to aid clinicians in diagnosing hemorrhagic stroke in the maternal population.

Stroke, Volume 56, Issue Suppl_1, Page AWP383-AWP383, February 1, 2025. Background and purpose:Vascular dementia (VaD) is one of the most common causes of cognitive decline, primarily resulting from cerebrovascular damage. Central to the pathogenesis of VaD are cerebrovascular endothelial cell (CEC) dysfunction, blood-brain barrier (BBB) disruption, and neuroinflammation. CD38, an enzyme involved in neuroinflammation and cellular senescence, has recently been implicated in these processes. However, its specific role in CEC dysfunction within the context of VaD remains poorly understood. We hypothesize that CD38 contributes to CEC dysfunction, BBB disruption, and cognitive decline in VaD, and that inhibiting CD38 could mitigate these pathological effects and improve cognitive outcomes.Method:We used a mouse model of VaD induced by bilateral carotid artery stenosis (BCAS). Mice were treated with the selective CD38 inhibitor 78c (10 mg/kg, twice daily for 1 month) to assess its therapeutic potential. CBF, BBB permeability, and cognitive function were evaluated. The expression of CD38, pro-inflammatory cytokines (IL-1β, IL-6, TNF-α), and CEC tight junction proteins were analyzed. In vitro experiments were conducted using CECs to investigate the effects of 78c on TNF-α-induced CD38 expression and inflammatory responses, focusing on the NOX4/eNOS signaling pathway.Result:Our results demonstrated that BCAS significantly reduced CBF, increased BBB permeability, and induced cognitive deficits, all of which were accompanied by elevated CD38 expression in CECs and heightened levels of pro-inflammatory cytokines. Treatment with the CD38 inhibitor 78c effectively mitigated these effects, resulting in reduced white matter damage, improved CBF, enhanced expression of CEC tight junction proteins, and decreased neuroinflammation and BBB disruption. In vitro studies further revealed that 78c attenuates TNF-α-induced CD38 expression and inflammatory responses in CECs, likely via the NOX4/eNOS signaling pathway.Conclusion:This study identifies CD38 as a crucial mediator of CEC dysfunction in VaD, linking chronic cerebral hypoperfusion to neurovascular damage. Targeting CD38 with the selective inhibitor 78c presents a promising therapeutic strategy for restoring vascular integrity and alleviating cognitive impairment in VaD. These findings not only highlight a novel molecular mechanism underlying VaD progression but also open new avenues for the development of targeted treatments for this debilitating condition.

Stroke, Volume 56, Issue Suppl_1, Page AWP374-AWP374, February 1, 2025. Introduction:The human microbiome has been studied in various diseases, including inflammatory bowel disease, diabetes, obesity, and cardiovascular diseases. However, its role in acute ischemic stroke (AIS) remains underexplored. This study aims to investigate the microbiome profiles in stool and saliva samples from AIS patients compared to control groups to identify distinct microbial patterns associated with ischemic stroke.Methods:We enrolled 54 AIS patients, collecting stool and saliva samples within one week of admission. Saliva was either self-expectorated (n=44) or obtained via oral swab (n=10) for those unable to spit. The 40 control group was defined as those without cerebrovascular disease, in whom no abnormalities were found on brain MRI/A taken for health check-up purposes within the past year. DNA extraction and 16S rRNA gene sequencing were performed, and data were analyzed using QIIME 2 for diversity and taxonomy, with Linear discriminant analysis Effect Size (LEfSe) for differential abundance and functional predictions.Results:AIS patients demonstrated significantly higher alpha diversity in stool samples compared to controls (p=0.001), indicating increased microbial richness. Saliva samples, however, showed decreased microbial richness in AIS patients (p=0.024). Beta diversity analysis revealed distinct microbial community structures between AIS patients and controls, especially at the genus level in stool samples (p=0.001). LEfSe analysis identified several bacterial taxa enriched in AIS patients’ stool, while saliva samples from AIS patients exhibited a higher number of depleted taxa compared to controls. Notably, the AIS microbiome showed reduced functional capabilities related to beneficial metabolic processes includingProteobacteria, Gammaproteobacteria, Enterobacteriaceae, andShigella, etc.These findings highlight a potential link between microbiome dysbiosis and the pathophysiology of AIS.Conclusions:This study identifies significant microbiome dysbiosis in AIS patients, characterized by altered diversity and bacterial composition in stool and saliva samples. The findings suggest that gut and oral microbiomes may contribute to the pathophysiology of cerebral infarction, warranting further investigation into their roles as potential biomarkers or therapeutic targets.

Stroke, Volume 56, Issue Suppl_1, Page AWMP93-AWMP93, February 1, 2025. Background:Chronic total internal carotid artery occlusion (CTO) can be associated with a high (22-25%) annual risk of stroke with limited therapeutic options. Total endovascular reconstruction (TER) is increasingly feasible but mid-term and long-term outcomes have not been reported.Methods:Data from all patients treated with carotid CTO treated with TER over the past 18years were collected in a database. Patients were selected based on the presence of angiographically proven symptomatic carotid occlusion, adequate landing zone and concurrent impairment of cerebrovascular reserve or recurrent ischemia despite maximal medical therapy. They were treated via a femoral approach using conventional CTO techniques with balloon expandable and/or self-expanding stents. Neurological evaluation of NIHSS, mRankin and carotid U/S were performed at discharge, 30days, and all subsequent follow-up. All TIA, stroke, death, and MI were recorded during follow-up. Angiographic follow-up was performed between 6-12months when possible.Results:Twenty-six symptomatic patients with a mean age of 65±7.8years were treated. Technical success was achieved in 22/26 (85%) on first attempt and in 3/4 on second attempt for total success rate of 25/26(96%). Total 30-day stroke/death/MI was 6.9% (2 ICH, both in first 3 years of experience). There were no recurrent events during 15.2±9.8months (median 12) of follow-up. Restenosis was found in 5/26 (19.2%) of patients; 2/5 were in unstented segments of the ICA. There was one case of asymptomatic carotid occlusion at 7months. The median mRS dropped from 2 to 1 at follow-up.Conclusion:TER is feasible in most patients with carotid CTO and is associated with a 30-day event rate lower than reported for STA-MCA bypass surgery. It is associated with good long-term stroke reduction despite a 19.2% risk of restenosis. Carotid re-occlusion is rare. Randomized trials are needed to validate this approach.

Stroke, Volume 56, Issue Suppl_1, Page AWP378-AWP378, February 1, 2025. Introduction:Subarachnoid hemorrhage (SAH) is associated with elevated morbidity and mortality. We previously showed that the immunomodulatory agent FTY720 improves neurological outcome in rats subjected to SAH.Hypothesis:FTY720 protects against SAH-associated neuronal cell death and white matter injury (WMI).Methods:We used the endovascular perforation model. Animals were divided into Sham, SAH-vehicle, and SAH-FTY720 groups. The SAH-FTY720 group received a single dose of FTY720 (0.5 mg/kg) intraperitoneally 3 hours after surgery. Brains were isolated and analyzed on day 7 post-injury. Neuroinflammation was ascertained by immunostaining for astrocyte (GFAP) and microglia (Iba-1) cell and the expression of proinflammatory mediators inducible nitric-oxide synthase (iNOS) through the NF-κB signaling pathway and TLR4. WMI was determined by quantifying the expression of myelin basic protein (MBP) and oligodendrocyte precursor cells (NG2). Neuronal death was determined by NeuN staining. Statistical analyses were performed with one-way ANOVA followed by Tukey’s post-hoc test using Graph Prism 10. Data are represented as mean±SD. Statistical significance was determined at the level ofp

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

Stroke, Volume 56, Issue Suppl_1, Page AWP2-AWP2, February 1, 2025. Introduction:Cathodal transcranial direct current stimulation (C-tDCS) is a potential neuroprotective method in the hyperacute phase of ischemic stroke. In rodent models, C-tDCS reduced final infarct volume and improved functional outcome. Our aim was to assess safety, tolerability, feasibility, and potential efficacy of C-tDCS in stroke patients with salvageable penumbra.Methods:Our study was a single-center, double-blind, randomized, sham-controlled (3 active: 1 sham), 3+3 dose-escalation trial. Inclusion criteria were stroke due to occlusion of the internal carotid or middle cerebral artery, last well-known time within 24 h, evidence of substantial penumbra on baseline CT perfusion, and ineligibility for mechanical thrombectomy. We applied C-tDCS at six dose tiers over the affected primary motor cortex (1 or 2 mA for 20 min in 1 to 3 cycles with 20 min breaks). The primary safety outcome was the symptomatic intracranial hemorrhage (SICH) rate at 24 h post-stimulation. The secondary safety outcomes were the rates of asymptomatic intracranial hemorrhage (AICH), early neurologic deterioration, serious adverse events, and mortality within 90-day follow-up. Tolerability was assessed by the rate of patients completing the entire stimulation period and by structured questionnaires. The success threshold for feasibility was median randomization-to-C-tDCS start time within 10 min in the last ten patients. Exploratory efficacy outcomes included infarct growth at 24 h, and National Institute of Health Stroke Scale (NIHSS) and modified Rankin Scale at day 90.Results:A total of 25 patients were enrolled (19 active, 6 sham), mean age (SD) 81 (12) years, 9 males, median NIHSS (Q1–Q3) 8 (6–16) points. Ten active and 4 sham patients were treated with thrombolysis. No SICH and 3 AICH (2 after thrombolysis) occurred in the active arm. We observed no significant difference in serious adverse events. The mortality rate was also comparable (4 active vs 2 sham patients). C-tDCS was well tolerated, all patients completed the stimulation period. Side effects were only mild and transient. C-tDCS was feasible, median randomization-to-C-tDCS start time was 8 (7–9) min. No significant differences in other outcome measures were observed.Conclusions:The application of C-tDCS in hyperacute ischemic stroke was safe, well tolerated, and feasible. Our results support the use of C-tDCS in larger efficacy trials.

Stroke, Volume 56, Issue Suppl_1, Page AWP399-AWP399, February 1, 2025. Background:The neuroinflammation triggered by acute cerebral ischemia can be mediated through inflammasome such as NLRP3 (NOD-like receptor family, pyrin domain containing 3) and ASC (apoptosis-associated speck-like protein). The NLRP3 inflammasome complex triggers caspase1-mediated maturation of cytokine. Chronic cerebral hypoperfusion induces upregulation of NLRP3 inflammasome and neuroinflammation. This study was undertaken to test our hypothesis that chronic cerebral ischemia in triggered inflammasome-mediated neuroinflammation, resulting in increased chronic ischemic injury. Furthermore, we undertook this study to demonstrate that NLRP3 inhibitor treatment reduces inflammasome-derived neuroinflammation and white matter damage caused by chronic ischemia.Methods:We used eight-week-old male C.B-17/Icr-Jcl mice in this experiment. The mice were subjected to sham or bilateral common carotid artery stenosis (BCAS) operation using microcoils with an internal diameter of 0.18 mm. At 3weeks after BCAS, these mice were sacrificed and examined by immunohistochemistry and western blotting (n = 5 for each group). In a separate set of experiments, mice were administered with 40 mg/kg of a NLRP3 inhibitor or vehicle daily for 3 weeks after BCAS. As before, the NLRP3 inhibitor and vehicle groups were compared by immunohistochemistry and western blotting (n = 5 for each group).Results:Cerebral hypoperfusion in BCAS mice induce upregulation of NLRP3, ASC, and upregulation of inflammasome-dependent IL-1β in the splenium of corpus callosum. In immunoblots and quantification of inflammasome proteins, the expression of NLRP3, ASC and IL-1β in ipsilateral brain lysates was increased after BCAS compared to the sham surgery group. Furthermore, the results of immunoreactivity showed that NLRP3 inhibitor treatment for BCAS mice reduced upregulation of NLRP3, caspase1 and IL-1β.Conclusions:These results suggest that chronic cerebral hypoperfusion induces upregulation of NLRP3 in the white matter lesion, likely leading to an increase of IL-1β. We also identified NLRP3 inflammasome inhibition as a novel mechanism to protective against chronic ischemic damage, can become a potential clinical benefit of therapeutic interventions.

Stroke, Volume 56, Issue Suppl_1, Page ATP200-ATP200, February 1, 2025. Background:Nontraumatic intracerebral hemorrhage (ICH) especially in deep locations is independently associated with a long-term increased risk of major arterial ischemic events. Minimally invasive surgery (MIS) has not been shown to improve outcomes for deep ICH. Whether ischemic events modify the effect of MIS on outcomes for deep ICH has not been studied.Methods:We pooled individual patient data from the MISTIE III (Minimally Invasive Surgery Plus Alteplase for Intracerebral Hemorrhage Evacuation Phase 3) and the ATACH-2 (Antihypertensive Treatment of Acute Cerebral Hemorrhage-2) trials. The exposure was ICH location (deep vs. lobar). The outcome was a symptomatic, clinically overt ischemic stroke or coronary ischemic event, adjudicated centrally within each trial. We evaluated the association between ICH location and risk of an ischemic event using Cox regression analyses after adjustment for demographics, vascular comorbidities, and ICH characteristics. We used logistic regression to assess whether ischemic events modified the effect of MIS with end of treatment volume (EOT)