Abstract WMP113: Investigating Cholesterol Dynamics in Post-Stroke Recovery through Optogenetic Neuronal Stimulation

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

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Gennaio 2025

Abstract 97: Association of Post-Stroke Cognitive Impairment with Impaired Glymphatic Function and Neurotoxin Waste Removal in Patients with Intracerebral Hemorrhage

Stroke, Volume 56, Issue Suppl_1, Page A97-A97, February 1, 2025. Objective:To evaluate a potential relationship between post-stroke cognitive impairment (PSCI) and a radiographic measure of glymphatic function after intracerebral hemorrhage (ICH).Introduction:PSCI has been less studied in patients with ICH. Here we aim to evaluate the role of glymphatic function after ICH and its association with PSCI. Glymphatic cleanup occurs in the perivascular space (PVS) formed by astroglial end-feet loosely surrounding small arteries and veins. Here we applied non-invasive diffusion tensor imaging (DTI) to measure changes in brain diffusion due to dynamics changes of interstitial fluid (ISF) and CSF along the PVS. The application of DTI-along the perivascular space index (DTI-ALPSI) has been validated to evaluate glymphatic function. It computes the diffusivity ratio between projection and association fibers oriented orthogonally with the medullary veins at the level of the lateral ventricle body (Fig-1A).Methods:We serially imaged 18 patients with deep ICH at 9.3±9.1 (V1) and 109±28 (V2) days of onset on a 3T MRI system. Cognitive assessment was obtained via MoCA scores. Fractional anisotropy (FA) and mean diffusivity (MD) maps were registered to the T1W and SWI images. Three regions of interest (ROI), remote from a lesion, in the association and projection fibers, orthogonal to the medullary veins at PVS were used to compute diffusivity (Fig-1C). Using the equation shown, the DTI-ALPSI was calculated. DTI-ALPSI = Mean (Dx proj, Dx assoc) / Mean (Dy proj, Dz assoc)Using 3D-Flair images, hematoma (HV) and edema (EV) volumes were segmented. The ipsilesional DTI-ALPSI was correlated with MoCA, HV, and NIHSS. Contralesional DTI-ALPSI was used as a control. A non-linear regression model was used for statistical analysis.Results:We enrolled 12M/6F with an average age of 49.3±13.3y. Compared to the control, the ipsilesional DTI-ALPSI was significantly decreased (p=0.036) at V2. Temporally the MoCA scores were significantly increased (19±8.5 to 23±6.0, p

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Gennaio 2025

Abstract TP122: Impact of 2021 Seconary Stroke Prevention Guidelines on Post Stroke Care Plans for Patients Transferred to Long Term Acute Care Facilities

Stroke, Volume 56, Issue Suppl_1, Page ATP122-ATP122, February 1, 2025. Background:Classification of etiologic ischemic stroke subtype guides post-stroke care and secondary prevention. Etiologic ischemic stroke subtypes are often not clearly documented in post-stroke care plans especially when transferring from one facility to another. In 2021, AHA/ASA published updated secondary stroke prevention guidelines recommending identifying etiologic ischemic stroke subtypes when possible. The impact of this on post-stroke care is unknown.Methods:Charts of all patients ages 18 and up, admitted from 1/1/20 to 5/23/21 and from 1/1/22 to 5/23/23 to 3 long-term acute care (LTAC) facilities, on antiplatelet therapy, and with an ascertainable history of stroke within 90 days of admission, were retrospectively reviewed to assess for documentation of ischemic stroke subtype at discharge/transfer to an LTAC facility and to assess for appropriateness of secondary stroke prevention therapies. Care plans from those two time periods were compared to assess for any impact the 2021 guidelines may have had on discharge practices.Results:Subtypes were not defined for the majority of ischemic strokes. Classification by etiologic subtype was observed in 33% of cases. Classification by territory or location was more common (Fig. 1). One-quarter of patients were on dual antiplatelet therapy (DAPT) and 75% of patients were on single antiplatelet therapy (SAPT) with more patients on DAPT in the latter time period (Fig. 2A). Rationale for DAPT were not provided for the majority of patients and NIHSS and ABCD2 scored were also not commonly provided for patients on DAPT (Fig. 2B). Close to 90% of patients were treated with antihypertensives and statin therapy at discharge to LTAC; 71% of patients were treated with diabetic therapies at discharge; stroke education at discharge to LTAC was documented for 43% of patients; and LDL was documented in 56% of patients (Fig. 3).Conclusions:Etiologic ischemic stroke subtypes were not documented for the majority of patients transferred to LTACs. Despite recent guideline revisions, an increase in documentation of stroke subtype was not observed. Optimal secondary stroke prevention strategies were difficult to assess without this information including appropriate antiplatelet regimens. Our findings highlight the importance of the need to improve post-stroke care plans at discharge and transfer including documentation of etiologic ischemic stroke subtypes to facilitate optimal post-stroke care across all transitions.

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Gennaio 2025

Abstract TP328: The Association between Post-ICH Continuation of Statin Use and Major Adverse Cardiovascular Events

Stroke, Volume 56, Issue Suppl_1, Page ATP328-ATP328, February 1, 2025. Objective:The role of statins in the management of intracerebral hemorrhage (ICH) remains controversial. We evaluated the association between post-ICH statin continuation and the development of major adverse cardiovascular events (MACE) in a cohort of Medicare fee-for-service ICH survivors.Methods:We identified Medicare-insured patients discharged alive with radiologically confirmed ICH who were taking statin pre index ICH event from the registry of a large stroke-certified healthcare system serving a diverse metropolitan area in Texas, United States (2016-2020). We longitudinally followed the patients by linking the registry data to the Center for Medicare&Medicaid Service (CMS) claims data. We used multivariable logistic regression models to report the adjusted odds ratio (aOR) and 95% confidence interval (CI) of predictors of post-ICH statin continuation, as well as the association of post-ICH statin continuation with the development of MACE (a composite outcome, including any stroke, acute myocardial infarction [AMI], systemic embolism, or vascular death) within 1-year of follow-up. Model fit was assessed using the Hosmer-Lemeshow test.Results:Among 142 eligible pre-ICH statin users (median age [IQR]: 77.5 [72-86] years; 57.0% female; 66.0% non-Hispanic White [NHW]), 59 (41.6%) continued using statin post-ICH (median age [IQR]: 76 [73-85] years; 57.6% female; 69.5% non-Hispanic White [NHW]), and 9 (6.3%) experienced MACE within 365-days. Patients with diabetes (aOR, 95% CI: 2.99, 1.25-7.15) and those with a history of anticoagulant use (2.54, 1.00-6.43) were significantly more likely to continue using statin post-ICH. However, obesity (0.30, 0.11-0.85) and higher comorbidity burden, as measured by the Charlson Comorbidity Index (CCI) (0.78, 0.68 – 0.90), were associated with lower odds of post-ICH statin use. Conversely, a higher age-adjusted CCI was significantly associated with lower odds of post-ICH statin use (0.92, 0.86 – 0.98). Post-ICH Statin continuation (vs. discontinuation) was associated with a non-significant decrease in the odds of developing MACE (5.1% vs. 7.2%; aOR, 95% CI: 0.67, 0.12-3.80). All the multivariable logistic models had a Hosmer-Lemeshow test p-value > 0.05, indicating a good fit.Conclusions:Continuation of statin post-ICH was associated with a non-significant decrease in the odds of developing MACE. Results from ongoing large clinical trials will elucidate the risks and benefits of the use of statins among ICH survivors.

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Gennaio 2025

Abstract TP115: Differences in the Medical Management of Post-Stroke Sequelae Among Patients Treated with Mechanical Thrombectomy vs Intravenous Thrombolysis

Stroke, Volume 56, Issue Suppl_1, Page ATP115-ATP115, February 1, 2025. Background:Mechanical thrombectomy (MT) as treatment for acute ischemic stroke (AIS) has demonstrated superior functional outcomes compared to intravenous thrombolysis (IVT). Yet AIS survivors often experience a range of unstudied post-stroke complications which negatively affect patient reported outcomes. To inform clinical practice, we assessed 90-day differences in the medical management of common stroke post-complications among patients treated with MT vs. IVT.Methods:A retrospective cohort of hospitalized AIS patients treated with IVT or MT were identified from Electronic Medical Records of 92 large healthcare organizations (01/2015-09/2024). Matched propensity scores were used to adjust for baseline differences across 36 factors. Outcomes included the use of medication(s) for the management of fatigue, spasticity, mood, sleep, seizure, neurogenic bowel&neurogenic bladder. Pre-specified subgroup analyses included differences in post-stroke sequelae management stratified by NIHSS scores of ≤9 (mild AIS) or >9 (moderate/severe AIS)&differences in post-stroke sequelae between AIS patients treated with MT vs MT + IVT.Results:The final cohort consisted of n=87,819 AIS patients treated with either IVT (n=82,534) or MT (n=5,285). PS matching resulted in 5,285 matched pairs with good balance across all baseline covariates. At 90-days, AIS patients treated with MT were more likely to receive medications for spasticity (RR: 1.15, 95%CI: 1.01, 1.31), mood (RR: 1.06, 95%CI: 1.01, 1.13)&neurogenic bowel (RR: 1.11, 95%CI: 1.09, 1.14) (Table 1). Approximately 7% (n=6,344) of AIS patients had NIHSS scores – PS matching resulted in 877 matched pairs with NIHSS ≤9&848 matched pairs with NIHSS >9. Following stratification, AIS patients treated with MT were significantly more likely to receive treatment of neurogenic bowel&bladder (Table 2). For the MT vs MT + IVT comparison, patients treated with MT were 5% less likely to receive treatment for neurogenic bowel RR: 0.95 (95%CI: 0.92, 0.99) among 1,900 matched pairs (Table 3).Discussion:Using real world data, AIS patients treated with MT (vs IVT) were more likely to receive treatment for spasticity, mood&neurogenic bowel. Among patients with documented NIHSS scores, differences remained significant for treatment of neurogenic bowel and bladder after stratifying by stroke severity. Healthcare providers should screen for these post-stroke sequelae, which substantially affect quality of life for AIS survivors.

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Gennaio 2025

Abstract TP113: Cerebellar Intermittent Theta Burst Stimulation in Post-Stroke Gait Impairment: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Stroke, Volume 56, Issue Suppl_1, Page ATP113-ATP113, February 1, 2025. Background:Persistent gait impairments affect nearly half of stroke survivors six months post-stroke, despite standard rehabilitation. Intermittent theta burst stimulation (iTBS), a specialized form of repetitive transcranial magnetic stimulation (TMS), has shown promise in enhancing neural circuit activity and promoting long-term potentiation. While traditionally targeting the primary motor cortex, recent studies suggest that cerebellar iTBS may further improve gait and balance by modulating cerebello-cortical pathways.Aim:This meta-analysis aims to evaluate the efficacy of cerebellar iTBS in improving gait and balance in stroke patients.Methods:We conducted a systematic search in PubMed, Embase, and the Cochrane Library until August 2024, following the recommendations in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Included studies were peer-reviewed randomized controlled trials (RCTs) that assessed the effects of cerebellar iTBS on balance, assessed using the Berg Balance Scale; gait, measured through 3D gait analysis and the Timed Up and Go (TUG) test; and activities of daily living, assessed via the Barthel Index, in post-stroke patients with persistent gait and balance impairments. Meta-analyses were performed using a random-effects model.Results:Seven RCTs involving a total of 230 post-stroke patients (iTBS group, n=115) were included in this meta-analysis. The analysis revealed a significant improvement in balance (standardized mean difference [SMD] = 1.20, 95% confidence interval [CI] 0.12 to 2.29, p = 0.03). However, the TUG test did not demonstrate a significant change (SMD = 0.04, 95% CI: -0.37–0.46, p = 0.83), potentially reflecting variability in baseline gait performance. The 3D gait analysis showed a favorable but non-significant trend towards step length improvement (SMD = 0.71, 95% CI: -0.82–2.23, p = 0.37). Notably, a significant enhancement was observed in activities of daily living (SMD = 1.24, 95% CI: 0.49–1.98, p = 0.001).Conclusions:This meta-analysis suggests that cerebellar iTBS significantly enhances activities of daily living in post-stroke patients, with a potential but less consistent impact on balance and gait. These findings highlight the promise of cerebellar iTBS as an adjunctive therapy in stroke rehabilitation, though further high-quality RCTs are needed to clarify its specific therapeutic benefits.

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Gennaio 2025

Abstract TP347: Sex differences of immunosuppression and phagocytosis after stroke as a correlative measure for post-stroke functional recovery

Stroke, Volume 56, Issue Suppl_1, Page ATP347-ATP347, February 1, 2025. Background:Stroke remains a leading cause of death globally, with significant sex differences in post-stroke outcomes. Additionally, post-stroke infections and sepsis are linked to differences in innate immune responses. The glycosidase, Chitotriosidase 1 (CHIT1), has emerged as an important regulator of innate immunity and lower levels of CHIT1 and chitinases-like proteins are associated with disease severity and progression including multiple sclerosis. However, whether CHIT1 plays a role in the response to acute ischemic stroke is unknown.Hypothesis:We hypothesized that sex-specific alterations in pro-inflammatory factors, including CHIT1, contribute to differential patterns of phagocytosis and post-stroke outcomes.Methods:We examined the effects of acute ischemic stroke (AIS) in older men and women, specifically circulatory cytokine production, circulatory phagocytosis assessment utilizing fluorescent bead engulfment assay, and if these correlated with post-stroke complications in peripheral blood mononuclear cells (PBMCs). We examined relationships with stroke severity, as measured by the NIH Stroke Scale (NIHSS) in patients with a NIHSS >6.Results:Our findings reveal that older women exhibit lower levels of CHIT1 activity correlating with poorer survival outcomes in AIS (p

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Gennaio 2025

Abstract TMP79: Post Thrombectomy Transcranial Doppler Parameters and Clinical Outcomes

Stroke, Volume 56, Issue Suppl_1, Page ATMP79-ATMP79, February 1, 2025. Introduction:Previous evidence indicated that transcranial doppler (TCD) parameters were associated with functional outcome in large vessel occlusion stroke (LVOS) patients who undergo mechanical thrombectomy (MT). We aim to 1) evaluate if TCD-derived pulsatility index (PI) and mean flow velocity (MFV) may predict clinical outcomes in LVOS after successful MT reperfusion, and to 2) assess if the PI is different in patients that received intravenous thrombolysis (IVT), indicating potential beneficial impact on microvascular reperfusion.Methods:This is a retrospective analysis of consecutive patients treated with MT for AIS secondary to a middle cerebral artery (MCA) M1 segment or intracranial internal carotid artery terminus (ICA) LVO. The study period spanned from January 1, 2018, to June 12, 2024; we only included patients with excellent reperfusion, defined as thrombolysis in cerebral infarction [TICI] grade 2c-3, who had TCD studies within 24 hours of their procedure. Patients without TCD studies, or with a poor temporal window were excluded. Ipsilateral and contralateral MFV and PI were collected for both the MCA and anterior cerebral artery (ACA). The primary outcome was the correlation between 3-month functional outcomes, assessed using the modified Rankin Scale (mRS), and the collected TCD parameters. Statistical correlations were performed using Pearson correlation.Results:Out of 1962 patients treated within the study period, 703 had MCA-M1 or i-ICA occlusions and TICI 2c-3, and only 229 had TCD within 24h and a good temporal window. Median age was 64.5 (IQR 56-75.5) years and 126 patients (55%) were males, 187 (81.7%) had an MCA-M1 and 42 (18.3%) an ICA-T occlusion. The median ASPECTS score was 8 (IQR 7-9) and the rate of IVT was 29.3%. Functional independence and mortality at 90 days were 49.3% and 14.4%, respectively. There was no association between MCA MFV (linear correlation coefficient -0.016;p=0.88) or PI (-0.08;p=0.47) and mRS at 90 days. The mean PI in patients that received IVT and did not receive IVT was comparable (mean 1.24 [SD0.06] vs 1.73 [SD0.54];p

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Gennaio 2025

Abstract TP114: Implementation of Evaluation and Treatment Package for Uniform Stroke Care and Outcomes in Medical Colleges in India (IMPETUSTROKE): Tele-Rehabilitation Model of Care for Post Stroke Patients

Stroke, Volume 56, Issue Suppl_1, Page ATP114-ATP114, February 1, 2025. Background and Aims:Globally, 87% of stroke patients are left with disability in low and middle-income countries. Continual rehabilitation is significant to maximize functional recovery. However, heterogeneity exists due to lack of guidelines, low prioritization of rehabilitation services, inadequate numbers of skilled rehabilitation specialists, limited health literacy, financial constraints and transportation limitations which leads to suboptimal rehabilitation. In this study we have presented tele-rehabilitation model of care for post stroke patients.Methods:IMPETUS stroke is an ongoing multicentric, prospective, multiphase, mixed-method, quasi- experimental implementation study intended to examine changes in a select set of stroke care-related indicators over time within 23 medical colleges in India. As a part of study, low cost model of tele-rehablitation services initiated using WhatsApp video communication. Periodic meetings with the collaborators and Rehabilitation teams had been done to outline the different strategies. Audio-visual training materials such as rehabilitation video and teaching manual are used as a study tool. Short specific videos had been crafted and finalized with the rehabilitation experts and collaborators specifically directed towards the post stroke recovery rehabilitation. Feasibility assessment will be done based upon the caregiver responses on the Client Satisfaction Questionnaire . Barthel Index, Stroke Rehabilitation Assessment of Movemement (STREAM) assessment and Modified Rankin Scale (mRS) will be used to assess the motor and functional outcomes.Results:A total of 731 patients provided the telerehabilitation services through live WhatsApp video conferencing after discharge. Initial assessments were done using Barthel Index, Stroke Rehabilitation Assessment of Movement assessment and Modified Rankin Scale at the time of discharge. Tailor-made exercise programs were prepared for each patient based upon the impairments. Primary caregivers were trained through on-patient demonstration and rehabilitation videos. One on one interactive and guided sessions were conducted on the 7th, 15th, 30th day of discharge in one month and then every once in a month for the next 2 months. The patient outcome data will be presented.Conclusions:The aforementioned tele-rehabilitation model of care will help to optimize motor and functional outcomes of the patient. Understanding the limitations and success of these interventions will be helpful.

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Gennaio 2025

Abstract TP360: Increased kynurenine levels are associated with post-stroke infection after controlling for potential confounders

Stroke, Volume 56, Issue Suppl_1, Page ATP360-ATP360, February 1, 2025. Introduction:Infections account for one-third of stroke deaths. Kynurenine pathway metabolites can modulate the immune response in other contexts. We previously reported a preliminary univariate analysis that showed only significantly elevated kynurenine concentrations among patients who developed a post-stroke infection (PSI), but no differences in other pathway metabolites. This study further characterizes the association between kynurenine and PSI.Methods:Using whole blood samples from acute ischemic stroke patients in the University of Colorado Emergency Medicine Specimen Bank, high throughput mass spectrometry determined kynurenine concentrations. Multivariable linear regression modeled the association between kynurenine and characteristics that could predispose patients to a PSI or alter kynurenine levels (age, sex, NIHSS score, time from sample collection to last known well, and a history of smoking, foley placement or mechanical ventilation, dysphagia, diabetes mellitus, immunosuppression, and chronic kidney disease). Multivariable logistic regression modeled the association between kynurenine and PSI while controlling for the above covariables.Results:Of 75 patients, 32% developed a PSI. Those without a PSI were similar in mean age (64.7+/-12.1years) and race (72.6% white) compared to those with a PSI (age: 69.5+/-13years; 58.3% white). However, patients varied in terms of sex (without PSI: 37.3% female; with PSI: 62.5% female; p=0.04), immunosuppression (without PSI: 5.9% immunosuppressed; with PSI: 20.8% immunosuppressed; p=0.05), and median NIHSS (without PSI: 3.3, IQR 3-7; with PSI: 6.5, IQR 6-7; p=0.03). Only age (point estimate 0.02, p=0.04) and history of chronic kidney disease (point estimate 7.57, p

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Gennaio 2025

Abstract TP379: Post-stroke whole body vibration therapy alters transcriptome and reduces ischemic brain damage in reproductively senescent female rats.

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

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Gennaio 2025

Abstract TP150: Association of Stroke Severity with Post-Stroke Depression and Household Size

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

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Gennaio 2025

Abstract 24: Iron deposition changes of ipsilateral ventral posterolateral nuclei correlate with central post-stroke pain after thalamic infarction

Stroke, Volume 56, Issue Suppl_1, Page A24-A24, February 1, 2025. Objectives:To investigate the correlation between iron deposition changes in the lesioned thalamic nuclei and the presence and severity of central post-stroke pain (CPSP) after thalamic infarction using quantitative susceptibility mapping (QSM) technique.Methods:We consecutively enrolled patients with unilateral chronic thalamic infarction with radiological examination conformed . Detailed and multidimensional pain characteristics measured as follows: Douleur Neuropathique 4 (DN4) questionnaire for validation of neuropathic pain diagnosis, Short-Form McGill Pain Questionnaire (SF-MPQ) for comprehensive representation of pain experience, Present Pain Intensity index (PPI) for current pain severity upon examination, and Visual Analogue Scale (VAS) for overall pain feeling since symptom onset. Age- and sex-matched stoke-free healthy controls were recruited simultaneously. High resolution structural image 3D-T1 BRAVO and QSM sequences were obtained with 3.0T MRI. The voxel-lesion-symptom-mapping (VLSM) was used to determine lesioned thalamic nuclei at the high risk for CPSP. Then ipsilateral QSM values of the whole thalamus and subregions were compared with contralateral side and healthy controls. Partial correlation analysis were performed to explore the relationship between QSM value and pain severity.Results:Finally, 28 CPSP patients, 33 non-CPSP patients and 55 healthy controls were included in the study. Our results indicated no significant difference in overall QSM values of the whole thalamus among the groups. The VLSM results showed lesion involving ventral posterolateral nuclei (VPL) was highly orrelaed with occurance of CPSP (pFWE=0.0092.). The QSM values of each subnuclei in the thalamus ipsilateral to infarction were lower compared with the contralateral side and healthy controls (p

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Gennaio 2025

Abstract TP398: RNS60 Substantially Reduces Early Vasogenic Edema, Mitigates Infarct Area, and Decreases Expression of HIF1α Four Days Post-Ischemic Stroke

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.

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Gennaio 2025

Abstract TP392: Prior recurrent hypoglycemia exposure potentiates post-ischemic hypoperfusion in male insulin-treated diabetic rats.

Stroke, Volume 56, Issue Suppl_1, Page ATP392-ATP392, February 1, 2025. Diabetes is a widespread disease, and stroke is one of the serious complications of diabetes. Antidiabetic therapy increases the risk of recurrent hypoglycemia (RH). We have previously shown that RH exposure leads to severe post-ischemic hypoperfusion at least up to 80 minutes after ischemia and increases the extent of ischemic brain injury in insulin-treated diabetic (ITD) rats. However, the total duration for which these perfusion deficits last is unknown. Thus, we evaluated cerebral blood flow up to 7 days post-ischemia in RH-exposed ITD rats using laser speckle imaging. Diabetic male rats were treated for hyperglycemia using insulin pellets, were assigned randomly to either hyperinsulinemic euglycemia (ITD+RH+Glucose control; n=7) or hyperinsulinemic hypoglycemia (ITD+RH; n=7) groups (3 h duration) (Figure B-C) and were subjected to transient global cerebral ischemia overnight after the last episode of hyperinsulinemic euglycemia or hyperinsulinemic hypoglycemia. We evaluated cerebral perfusion at baseline (pre-ischemia), 1 h, 24 h, 3 d, 5 d, and 7 d post-ischemia. The cerebral ischemia in RH-exposed ITD rats resulted in a significant decrease in percentage change in cerebral blood flow as compared to the control rats when quantified 1 hour (23%, p

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Gennaio 2025

Abstract TP370: Deep Learning Applied Analysis of Post-Stroke Mice During Corner Test Provides Quantitative Assessment of Locomotion

Stroke, Volume 56, Issue Suppl_1, Page ATP370-ATP370, February 1, 2025. Introduction:Despite efforts to improve stroke outcomes in patients, a translational gap exists between preclinical and clinical studies. Due to this gap, the Stroke Preclinical Assessment Network has incorporated the corner test (CoT) for behavioral outcome as a primary measure for evaluating whether a treatment is successful or not. Standard behavioral analysis for CoT uses the laterality index to detect if there is mouse turning preference on a scale from -1 to 1. We sought to determine if a deep learning approach using “DeepLabCut” could be applied towards enriching our CoT data to better evaluate aspects of mouse locomotion.Methods:Six C57/Bl6 mice were subjected to an 1 hr transient middle cerebral artery occlusion in the right hemisphere of the brain. CoT were recorded with an isometric view and performed at both baseline (BL) prior to the stroke and one day post stroke (D1). The same set of six mice performed 10 turns per CoT, totalling to 60 turns for BL and 60 turns for D1. The pose estimation model was made using a ResNet-101 neural network trained on 1064 manually-labeled frames, with the assistance of “DeepLabCut” software packages. Videos were analyzed by the pose estimation model and sequentially processed through a newly developed R script and DLC Analyzer R script. Turns were defined as in SPAN with a 90 degree head turn upon vibrissae contact on both sides of the corner boards. Turn latency was defined as the time lapsed during a turn, and head turn speed as the average speed during a turning event.Results:The average laterality index showed clear preference towards ipsilateral turning in all D1 mice (-1.0 ± 0.04, N = 6). Furthermore, a comparison between BL data and respective D1 data showed significantly longer turn latencies and slower head turn speeds (p < 0.05) for D1 mice. The average turn latency for BL mice was 3.58 ± 0.57 s, which was 4.6 times shorter than that of D1 mice (16.45 ± 3.11 s). The average speed for BL mice was 2.01 cm/s ±0.21, which was 2.3 times faster than that of D1 mice (0.86 ± 0.14 cm/s).Conclusion:This deep learning approach enriches current stroke behavioral analysis methods by offering additional quantitative information upon which behavior can be assessed. Future studies can use these behavioral metrics for stratification or correlation with variables of interest (e.g. infarct size) to provide a more refined assessment of preclinical stroke behavior.

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Gennaio 2025