bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract TP304: Ischemic Stroke Increases Levels of One-Carbon Enzymes and the Folate Receptor in Male and Female Brain Tissue
Authors: Burrows Petter , Dhillon Himmat , Covalesk Amanada , Manfredi Lilah , Beach Thomas G , Serrano Geidy , Jadavji Nafisa M
Published: February 2024

Stroke is the second most common cause of death worldwide and predominantly affects individuals over 65 years old. Its prevalence is projected to increase in parallel with the aging global population. Nutrition is a modifiable risk factor for ischemic stroke. Folates, B-vitamins and choline play a central role in one-carbon (1C) metabolism, which is a key metabolic network that integrates nutritional signals with biosynthesis, redox homeostasis, epigenetics, regulation of cell proliferation, and stress resistance. Our research group has previously shown that deficiencies in 1C lead to worsened stroke outcomes using preclinical models. However, the impact of ischemic stroke on 1C enzymes remains unknown. The objective of this study is to investigate whether ischemic stroke contributes to a change in the levels of 1C enzymes after ischemic stroke in male and female patients. Brain tissue sections from ischemic stroke patients and controls were stained, all tissue was co-stained with neuronal nuclei (NeuN) and DAPI (4′,6-diamidino-2-phenylindole). The colocalization of all three markers was evaluated by two individuals who were blinded to the experimental groups. Ischemic stroke increased neuronal levels of the folate receptor and 1C enzymes, methylenetetrahydrofolate reductase (MTHFR), thymidylate synthase (TS) and serine hydroxymethyltransferase (SHMT). In male stroke brain tissue was observed to have increased levels of MTHFR, TS, and SHMT. Female brain tissue had increases in the folate receptor and TS. The results suggest that ischemic stroke leads to increased demand on 1C and that there are some small differences between males and females.
Abstract TP310: Prnd in Angiogenic Brain Endothelial Cells is Involved in Neurovascular Repair After Ischemic Stroke
Authors: Kim Sehee , McCarty Joseph
Published: February 2024

Introduction:
The prion protein family member doppel (encoded by the Prnd gene) is essential for the control of angiogenesis during CNS development and has been implicated in pathological angiogenesis. Various data demonstrate that Prnd expression is linked to physiological angiogenesis by regulating VEGFR2 signaling. However, the roled for Prnd in pathological angiogenesis after ischemic stroke is not known. Therefore, we hypothesized that Prnd contributes to stroke-induced brain injury repair by regulating angiogenesis.

Methods:
We induced ischemic injury in Prnd+/+ and Prnd-/- mice by middle cerebral artery occlusion for 30 minutes. Infarct volume was measured three days and 28 days after stroke and survival rates were analyzed. We also measured the expression of Prnd and angiogenesis-related factors (VEGF, VEGFR2, and VE-Cadherin) in control and Prnd-/- brains. We also determined the activation and localization of pericytes, oligodendrocytes, and astrocytes in brain sections after ischemic stroke.

Results:
Prnd-/- mice showed worse survival rate than Prnd+/+ mice after ischemic stroke. At three days post-stroke, infarct volume in Prnd-/- and Prnd+/+ mice was similar, but brain infarct volume of Prnd-/- mice was increased at 28 days. Interestingly, Prnd mRNA levels were significantly increased in the ipsilateral region of the brain of Prnd+/+ mice at three days post ischemic stroke. VEGFR2 mRNA expression increased in the Prnd+/+ brain, but this increase was observed to a higher extent in the Prnd-/- brain. Also, the levels of VE-Cadherin which is an essential component of adherens junctions and modulates the VEGFR function in Prnd+/+ was increased in the ipsilateral region compared to contralateral, but not in Prnd-/-mice.

Conclusion:
Our results indicate that Prnd deficiency is associated with poor stroke outcome and that increased Prnd expression after ischemic stroke is involved in brain injury repair by regulating angiogenesis-related signaling pathways. The data also suggest that Prnd-controlled angiogenesis may be a potential mechanism to improve outcomes after ischemic stroke.
Abstract TP314: The α5 Integrin Inhibitor ATN161 Mitigates SARS-CoV-2- Induced Brain Endothelial Barrier Disruption and Neuroinflammation α5 Integrin Inhibitor ATN 161
Authors: Umar Meenakshi , Amruta Narayanappa , Gressett Timothy E , Volic Milla , Ouvrier Blake , Ismael Saifudeen , Talkington Grant , Bix Gregory J
Published: February 2024

Introduction:
Although SARS-CoV-2 infection can cause a wide range of mild to severe symptoms, the pathophysiology of acute and long-term neurological manifestations remains elusive. The arginine-glycine-aspartic acid motif of the viral spike protein may use to bind integrins receptors in the CNS, which play an important role in cerebrovascular integrity. Here we investigate the role of integrin α5β1 in mediating brain endothelial damage and inflammation during SARS-CoV-2 infection.

Method:
Mouse brain microvascular endothelial cells (bEnd.3) were treated with SARS-CoV-2 (Isolate USA-WA1/2020) or delta variant spike protein for 24h then later exposed to hypoxia for 6h (to model the effects of in vivo pulmonary infection). Cells were pretreated with ATN-16, 1h before SARS-CoV-2 and hypoxia challenge. Further, BALB/c mice were inoculated intranasally with 2x10
4
-PFU of the MA-10 strain of SARS-CoV-2 and treated with 1mg/kg of ATN-161, an α5β1 integrin inhibitor, retro-orbitally. The brains were collected 3 days post-infection for neuropathological evaluation.

Results:
SARS-CoV-2 and delta variant spike protein inoculations induced integrin α5 and decreased claudin-5 expression in bEnd.3 cells in a dose-dependent manner. SARS-CoV-2 spike protein challenge at 0.5 μg for 24h followed by hypoxia for 6h resulted in increased α5 and decreased claudin-5 expression in either hypoxia or SARS-CoV-2+hypoxia combination. ATN-161 (10μM) pretreatment inhibited SARS-CoV-2+hypoxia-induced α5 upregulation and restored claudin-5 loss in bEnd.3 cells. The
in
vivo
studies showed a significant increase in the pro-inflammatory response as measured by cytokine IL-6 expression and a decrease in barrier integrity by tight junction claudin-5 expression in the brains of MA10-infected mice compared to mock controls. ATN-161 treatment decreased IL-6 expression and increased claudin 5 expression in infected mice.

Conclusion:
Therefore, we propose that targeting integrin α5β1 through inhibitors such as ATN-161 offers a promising therapeutic strategy for attenuating SARS-CoV-2 and its immunological impact on brain vasculature. This approach may be pivotal in reducing both acute and chronic neurological morbidities associated with COVID-19.
Abstract TP316: Treatment With Tamoxifen, a Selective Estrogen Receptor Modulator, Has a Cell Type-Specific Effect on Mitochondrial Stress From Oxygen Glucose Deprivation in Astrocytes and Microglia
Authors: Zardeneta Macy E , Branyan Taylor , Sohrabji Farida
Published: February 2024

Introduction:
Tamoxifen (TAM), a selective estrogen receptor modulator, is a first-line treatment to prevent recurrence of hormone receptor positive breast cancer. Stroke risk is increased in women with low estrogen and doubles in women after the age of 55 (average age of menopause). Critically, women taking TAM as breast cancer therapy had increased risk of ischemic stroke (82%). We hypothesize treatment with TAM will increase stroke severity, which is associated with increased blood brain barrier (BBB) damage and worsened neuroinflammation. We investigated effects of TAM on mitochondrial stress and cellular function in astrocytes and microglia, key cells of the BBB and neuroimmune response, respectively.

Methods:
Cultured female human astrocytes and HMC3 microglia were treated with TAM (1uM), 17ß-estradiol (10nM, E2), or vehicle (DMSO) for 24 hours. Cells were separated into two groups: normoxic (21% O
2
, 25mM glucose) or oxygen and glucose deprivation (OGD) conditions 6 hours before analysis. Mitochondrial function was assessed using a Seahorse XFe96 Analyzer. Microglial expression of mitochondrial proteins (Complex I & III and DRP1) was analyzed with western blot, and function was assessed with flow cytometry after
in vitro
phagocytosis of pHrodo red zymosan.

Results:
TAM reduced maximal (p =0.0174) and basal respiration (p =0.0149) under OGD conditions in microglia compared with DMSO or E2 treatment. However, in astrocytes, maximal and basal respiration were increased in OGD (p =0.0003, p =0.0002). There was no significant difference in expression of mitochondrial proteins or phagocytic function in HMC3 microglia under either normoxic or OGD conditions after TAM treatment.

Conclusions:
TAM treatment resulted in a cell type-specific alteration in mitochondrial stress response. Since mitochondrial stress is a hallmark of stroke pathophysiology, and microglia and astrocytes are among the earliest cells to respond to ischemia, treatment with tamoxifen might alter the cellular environment, by its divergent actions on these two cell types, leading to worsened stroke outcomes. These data support the need for
in vivo
investigation to elucidate the mechanism by which TAM is altering cellular response. Support: RFAG042189 to FS, 1F30NS131053 to MEZ
Abstract TP321: Real World Outcomes in Patients With a Posterior Cerebral Artery Occlusion With a Low NIHSS
Authors: Patel Karan , Taneja Kamil , Shu Liqi , Koneru Manisha , Dasgupta Savanna , Jafri Neda , Yaghi Shadi , Nguyen Thanh , Schumacher Hermann C , Shaikh Hamza , Tonetti Daniel , Oliveira Renato , Khalife Jane , Siegler James E
Published: February 2024

Introduction:
Observational studies have reported improved outcomes following endovascular treatment (EVT) for posterior cerebral artery (PCA) occlusions. Whether there is a benefit of EVT in patients with NIHSS <6 is less well understood.

Methods:
The National Inpatient Sample (2015-2020) was retrospectively queried for patients with a primary PCA occlusion with a NIHSS <6 and age>17 without a concomitant basilar artery occlusion (BAO). A secondary analysis including patients with a BAO was also performed. Treatment with best medical management (BMM) versus endovascular therapy (EVT) was compared using propensity score matching.

Results:
In this time frame, 31,175 patients presented with a PCA occlusion as the primary diagnosis and had a NIHSS<6. Of these patients, 8.8% of patients were treated with EVT. 31,050 patients did not have a concomitant BAO. In a propensity matched cohort of primary PCA and patients without a concomitant BAO, 2720 were treated with EVT and 2720 were treated with BMM. Patients treated with EVT had greater odds of routine discharge (adjusted OR 1.34, 95% CI 1.02 to 1.77, p=0.036) with no difference in length of hospital stay (adjusted β -0.35, 95% -0.83 to 0.13, p=0.15) or in-hospital death (adjusted OR 0.77, 95% CI 0.15 to 3.99, p=0.76) as compared to patients treated with BMM. Patterns were also similar when patients with a concomitant BAO were present (routine discharge adjusted OR: 1.67, 95% CI: 1.28-2.19, p<0.001).

Conclusions:
Our findings suggest potential real-world benefit for EVT in patients with a PCA occlusion with a low NIHSS, irrespective of concomitant BAO.
Abstract TP33: Knockout of Kruppel-Like Factor 4 in Brain Endothelial Cells Accelerates Vascular and Neuronal Degeneration During Aging
Authors: Vázquez-Rosa Edwin , Dhar Matasha , Liao Xudong , Chakraborty Suwarna , Tripathi Sunil J , Fang Hua , Shin Min-Kyoo , Koh Yeo Jung , Miller Emiko , Tang Xinmiao , Sridharan Preethy , Chaubey Kalyani , Barker Sarah , Franke Kathryn , Cintron-Perez Coral , Padmanabhan Roshan , Haragopal Hariprakash , Flanagan Margaret E , Jain Rajan , Winters Bradley D , Wilson Brigid , Paul Bindu , Jain Mukesh , Pieper Andrew
Published: February 2024

As we get older, various aspects of our bodies start to decline, including brain function. The mechanisms behind the decline in brain function due to aging are still not well understood. The blood-brain barrier (BBB) is crucial for maintaining brain health and homeostasis by controlling both passive and active exchange of materials between the blood and brain. This barrier is predominantly composed of endothelial cells, which deteriorate in both aging and neurodegenerative disorders. Endothelial cells are also highly enriched in the Kruppel-like factor 4 (KLF4) transcription factor, which is reduced in expression as we age. In this study, we report that endothelial-specific KLF4 KO mice demonstrate accelerated brain aging, including accelerated BBB deterioration, neurodegeneration, and cognitive decline. Single-cell RNA sequencing from brain endothelial cells of endothelial-specific KLF4 KO mice demonstrate aberrantly high expression of adaptive and innate immune response genes, and live animal brain imaging across the lifespan reveals accelerated aging-related BBB deterioration, decreased blood flow, and impaired neurovascular coupling. Endothelial-specific KLF4 KO mice show increased neuroinflammation and neutrophil infiltration. Our data suggest that diminished endothelial cell KLF signaling with age could be a novel therapeutic target to preserve health and function of the aging brain.
Abstract TP34: Outcomes and Trends of Subarachnoid Hemorrhage During the COVID-19 Pandemic
Authors: Patel Smit D , Balabhadra Anvesh , Otite Fadar , Patel Neel , Tunguturi Ajay , Bruno Charles , Sussman Eric , Ollenschleger Martin , Alberts Mark J , Mehta Tapan
Published: February 2024

Background:
Hemorrhagic cerebrovascular manifestations are known to be associated with COVID-19. Our study aims to describe the trends and outcomes of patients with Subarachnoid Hemorrhage (SAH) using a Nationwide Inpatient Sample (NIS) database.

Methods:
We examined the 2016-2020 NIS database, focusing on patients aged 18 years and older with a primary SAH discharge diagnosis. Comparative outcome analyses between pre-COVID (2016-2019) and COVID year (2020) were performed. NIS-Subarachnoid Hemorrhage Severity Score (NIS-SSS) was used as a surrogate marker for the modified Rankin Scale.

Results:
Our analysis of 119,005 patients with subarachnoid hemorrhage (SAH) unveiled a median age of 59.6 years with 72,650 (61.0%) being female. Comparisons across age (p=0.867), gender (p=0.08), and length of stay (p=0.130) showed no significant differences between groups. Median NIS-SSS score was 3.6, revealing an increase from pre-COVID 3.3 to COVID 5.6 (p=0.0006). Adjusted analyses exhibited similar inpatient mortality (COVID vs. pre-COVID: OR 0.98, 95% CI 0.89-1.08, p=0.71). However, advancing age (OR 1.01, p<0.001), NIS severity score >10 points (OR 11.11, p<0.001), CHF (OR 1.47, p<0.001), coagulopathy (OR 1.47,p<0.001), cocaine use (OR 1.46, p=0.001), and weekend discharges (OR 1.09, p=0.04) were linked to increased mortality odds. In 2020, non-COVID SAH rates remained stable (9.2% - 9.4%, Ptrend=0.42), while COVID-associated SAH surged (1.2% - 21%, Ptrend=0.023).

Conclusion:
Our study finds no disparity in outcomes for patients hospitalized with aneurysmal subarachnoid hemorrhage (aSAH) during the COVID-19 pandemic when contrasted with the preceding years. However, a substantial rise in SAH admissions among COVID-19 patients is evident. Exploring the physiological reasons behind this observed trend could be a crucial avenue for further investigation.
Abstract TP50: Ensuring Safe Post-Procedure Throughput for CEA and CAS Patients
Authors: Beland Dawn K , Albert Siobhan
Published: February 2024

Background:
A new policy was implemented in November 2021 to reduce the length of post-anesthesia-care-unit (PACU) stay from 6 hours to 4 hours to reduce the nursing care burden and decrease the length of stay, yet how it affected patients’ events after PACU discharge needed close evaluation. Thus, the QI project aimed to retrospectively examine unexpected or safety events of patients who underwent carotid artery stenting or carotid endarterectomy procedures before versus after implementing the new policy.

Objective:
To compare and examine the rates of unexpected or safety events that occurred before (5/1/2021 - 10/31/2021; PRE) vs. after (2/1/2022 - 7/31/2022; POST) adoption of the new policy.

Methods:
A determination of IRB review was granted for the retrospective QI project. The unexpected or safety events included patient issues (rapid response calls, STAT calls to service, or bounce back to a higher level of care) and issues with VS or neuro assessment variability. For group comparison, Fisher’s Exact tests were used for dichotomous information, and the Mann-Whitney U tests were performed for continuous data.

Results:
A total of 145 patients were identified during the study period composing 75 (51.7%) PRE and 70 (48.3%) POST patients. The rates of VS or neuro assessment variability were similar in both groups (PRE: 1.3% vs. POST: 1.3%,
p
=1.000). Though we saw a lower rate of patient issues within 24 hours on the floor in POST (4.3%), the difference was not statistically significant (PRE: 8.0%,
p
=0.496).

Conclusion:
Inefficient patient throughput can impact currently strained hospital resources. Findings of the QI project confirmed that the new policy did not incur a higher rate of instability on the nursing unit. This data lends confidence to Vascular Surgery and Stroke programs as they seek to streamline patient care and manage hospital resources.
Abstract TP56: Addressing Written Stroke Education and Post-Discharge Prescription Filling for Ischemic Stroke Survivors
Authors: Atkins Mikaela , Sheehan Tiffany O , Morgan Michelle S
Published: February 2024

Background:
Poor adherence to prescribed medication and prescription filling can have dire consequences on patient outcomes. It is important that patients understand how their medications reduce the progression or worsening of their diagnosis. Understanding can be enhanced through literacy assessment and implementation of educational materials. At a CSC, it was identified that only 33% of Acute Ischemic Stroke (AIS) and TIA survivors filled new prescriptions within one week of being discharged home.
Purpose
To evaluate inpatient written stroke education book for its health and grade literacy, make targeted modifications, then assess its impact on prescription filling within one week of discharged home for stroke survivors.

Methods:
We conducted a pre-post design EBP QI project. The original and modified book was evaluated using the Patient Education Materials Assessment Tool (PEMAT) and the Flesh-Kincaid Grade Level (FKGL) tool. Based on these scores, targeted modifications were made to remove content, add infographics, and free text areas. The modified book was implemented in October 2023. Group one received the original book between Jan-May 2021, while group two received the modified book between November 2022-Jan 2023. Prescription filling rates were collected from post-discharge phone-call questionnaires and included AIS and TIA survivors, discharged home,
>
18 years of age, and completed the phone call questionnaire. Mann-Whitney two-sample rank-sum test was completed to assess for statistical significance among groups. Statistical significance was set at 0.05.

Results:
Prior to the book revisions the FKGL was at the 11
th
grade level, and the PEMAT scores indicated 55.3% understandability, and 56% actionability. Following modifications, the FKGL was at the 7
th
grade level, and the PEMAT scores indicated 89.9% understandability and 95% actionability. The rate of prescriptions filled was evaluated pre (n= 98, 33%) and post modification (n=52, 56%) and was statistically significant (U= 1959, z=-2.73, p=0.006).

Conclusion:
Addressing the literacy and grade level of written stroke education improved prescription filling in AIS and TIA survivors discharged home. Further research may focus on additional barriers to prescription filling.
Abstract TP65: Mastering the Art of Herding Cats: Unraveling the Methods of Effective Communication in a Growing Stroke Program
Authors: Stenuf Chaeli , Langston Sarah J , Sowers Sabriya , Houghton Margaret
Published: February 2024

Background:
Since becoming a Comprehensive Stroke Center in 2008, our annual stroke patient volume doubled, and intervention volume grew nearly 6-fold. The program achieved multiple milestones over this time, transitioning from a combined ICU-progressive care unit to separate specialized units, and later relocating to a new facility with a dedicated Neuro ICU and two progressive care units. As the program expanded, innovative communication techniques and processes were adopted to accommodate the growing staff and infrastructure.

Methods:
The development and dissemination of intervention reports to stakeholders from each stroke case heightened awareness of time goals and fostered collaboration. Effective communication was further facilitated through the development of a SharePoint site, newsletter, and electronic handbook. Strategically designed dashboards provided crucial data on volumes, diversion, and treatment times. QR codes were introduced for convenient data and research request access. Moreover, detailed electronic follow-up reports facilitated external collaboration with referring facilities.

Results:
Embracing electronic communication enhanced information sharing, improving our team’s grasp of program data, outcomes, launches, and outreach initiatives. The monthly newsletter achieved a 60% open rate, contributing to nearly 5,000 SharePoint site visits. Monthly intervention reports to stroke team responders heightened time goal awareness, fostering collaboration, improving documentation, and reducing the need for case delay documentation clarification. Sending an average of 71 follow-up reports monthly to referring hospitals and EMS agencies strengthened external partnerships. Moreover, leveraging social media amplified community outreach for stroke education.

Conclusion:
We have found electronic communication to be successful for our growing program. To enhance engagement and accommodate diverse learners, we recommend utilizing a range of methods, including visuals, quizzes, and interactive content. Future plans involve expanding communication strategies with emerging techniques and conducting a formal analysis to assess stakeholders' comprehension of shared information in stroke care.
Abstract TP81: Retrospective Gender Disparity Study Evaluating Arterial Size and Post Stroke Outcomes
Authors: Berns Holly , Catapano Joshua , Ducruet Andrew , Becker Tim
Published: February 2024

Introduction:
Mechanical thrombectomy is now the standard of care for eligible large vessel occlusion (LVO) patients, but women are less likely to be independent at 90-days and have worse functional outcomes compared to men (Modified Rankin Scale (mRS) > 2). The factors that contribute to this disparity, including arterial size, have not been thoroughly explored and these factors are critical to understand for developing new thrombectomy technologies and techniques.

Methods:
Retrospective data from Barrow Neurological Institute was analyzed to determine the correlation between arterial diameters and the clinical outcome at 90-days of six patient groups (males vs. females: ages 18-40, 41-65, and 65+) after mechanical thrombectomy. Patients were adults who underwent aspiration thrombectomy for LVO within the past 3 years (verified with documented and calibrated computerized tomography (CT) and angiography) and had a documented 90-day mRS score. Vessel diameters were measured from calibrated patient CT scans and conventional angiograms. After adjusting for critical factors (such as demographics, pre-stroke mRS, and use of rTPA), a multiple logistic regression analysis was implemented to determine the correlation between arterial diameter and the 90-day clinical outcome.

Results:
The data suggests a correlation between arterial diameters and the efficacy of currently available thrombectomy systems. With cerebral vessel anatomical diameters documented as statistically smaller in women versus men, these results play a role in the worse outcomes seen in women.

Conclusion:
Currently available mechanical thrombectomy systems may not be optimized for patients with smaller arterial sizes as compared to patients with larger arterial sizes. Future devices with improved navigation and patient-specific size-adaptive capabilities may lead to improved patient outcomes.
Abstract TP89: Participation in Kitchen-Related Tasks Among Stroke Survivors: A Qualitative Study
Authors: Lo Suzanne H , Chau Janita Pak Chun
Published: February 2024

Background and Aim:
Being able to prepare meals and perform kitchen-related tasks is essential for living independently after stroke, yet receiving less attention when compared with other self-care activities such as toileting. This study sought to understand the survivors’ experiences of how they performed kitchen-related tasks after stroke.

Methods:
A qualitative study with individual, semi-structured interviews were conducted with a convenience sample of adults who had had a first or recurrent ischemic or hemorrhagic stroke for over one year and were living at home. The survivors shared about their participation in kitchen-related tasks after stroke including boiling water for drinking, meal preparation, and kitchen-related cleaning. Non-participant observation of activities performed by the survivor on a random day was conducted. Assistive aids used by the survivors and home modifications made to facilitate them to perform kitchen-related tasks were recorded. All interview data were transcribed verbatim and analyzed thematically.

Results:
Twenty survivors with a mean age of 61.40 years old (SD=8.52) were interviewed. They had had a stroke for an average of 10 years (SD=7.33). Four main themes were identified: 1) Being able to prepare meals symbolized achievement of independence in daily living and recovery, and eager to be able to do it. 2) Simple cooking or minimal participation in kitchen-related tasks even two to three years after stroke, feeling dependent in choices of food. 3) Common factors affecting their participation included being hesitant, barred by family members, safety concerns, reduced activity tolerance to stand during cooking, and inconvenience or inabilities to perform tasks with one hand such as cutting food, or holding a kettle filled with water. 4) Limited knowledge regarding adaptive tools facilitating their performance of kitchen-related tasks. More suggestions on cost-effective and pragmatic strategies and tools to prepare meals with one hand were desired.

Conclusions:
The findings suggested that the chronic stroke survivors had inadequate knowledge and skills to perform kitchen-related tasks. Suggestions on appropriate use of adaptive tools for cooking with one hand and innovative skill training are needed.
Abstract TP92: Feasibility of a Poststroke Without-Fail Care Rate to Assess Rehabilitation and Follow-Up Care
Authors: Groves Christine , Seigel Courtney R , Bartlett Stephanie , Williams Linda S , Parrott Devan R , Comer Amber R
Published: February 2024

Introduction:
Large cohort studies show substantial variability in poststroke care. We developed a guideline-based poststroke without-fail care rate (PWR) to measure rehabilitation and follow-up care quality (Table 1). Our primary aim was to test PWR feasibility to measure guideline-concordant poststroke care among individuals discharged from an urban safety net hospital. Secondarily, we evaluated socioeconomic strain’s (SES) relationship with PWR.

Methods:
We reviewed electronic medical records of individuals with acute ischemic stroke (AIS) admitted to an urban safety net hospital from July 1 - August 31, 2022. Individuals were given a pass/fail or ineligible for each process. The PWR, calculated per individual, was passes/total number of eligible processes (score 0-1.0).

Results:
Out of 30 persons with AIS, 20 were eligible for PWR assessment (Table 2). Mean PWR was 0.598 (SD .210, range .273-.900). Most processes were readily available, with no observable floor or ceiling effects. Lowest pass rates were seen in therapy continuance, PCP follow-up, blood pressure control, and exercise. The PWR difference between individuals with SES (M = .443, SD =.135) and without SES (M = .634, SD = .246) lacked statistical significance but demonstrated a high effect size; t(10) = 1.66, p = .064, d = .961.

Conclusion:
The PWR is a feasible tool to assess quality of poststroke care and may be useful to identify and evaluate interventions to improve equity and quality of poststroke care. The high effect size of SES warrants further examination in a larger sample.
Abstract TP99: Implementing Telestroke in the Inpatient Setting: Identifying Factors for Success
Authors: Pestka Deborah , Ramezani Solmaz , Boes Sam , Peters Maya , Usher Michael G , Koopmeiners Joseph , Beebe Timothy , Streib Christopher D , Melton Genevieve
Published: February 2024

Background:
Inpatient telestroke programs have emerged as a solution to provide timely stroke care in underserved areas, but their successful implementation and factors influencing their effectiveness remain underexplored. This study aimed to qualitatively evaluate the perspectives of inpatient clinicians located at the spoke hospital who were participating in a newly established inpatient telestroke program in order to identify implementation barriers and facilitators.

Methods:
This was a formative evaluation relying on semi-structured qualitative interviews with sixteen inpatient providers (physicians and nurse practitioners) that have utilized inpatient telestroke services. Interviews were conducted with providers at spoke sites of a hub-and-spoke inpatient telestroke program. The Integrated-Promoting Action on Research Implementation in Health Services (i-PARIHS) framework guided data analysis, focusing on the innovation, recipients, context, and facilitation aspects of implementation. Interviews were transcribed and coded using thematic analysis.

Results:
Fifteen themes were identified in the data and mapped to the i-PARIHS framework. Themes related to the innovation (telestroke program) included easy access to stroke specialists, the benefits of limiting patient transfers, concerns about duplicating tests, and challenges of timing inpatient telestroke visits and notes to align with discharge workflow. Themes pertaining to recipients (care team members and patients) were communication gaps between teams, concern about the supervision of advanced practice providers, and challenges with nurse empowerment. With regards to the context (hospital and system factors), providers highlighted familiarity with telehealth technologies as a facilitator to implementing inpatient telestroke, yet highlighted resource limitations in smaller facilities. Facilitation (program implementation) was recognized as crucial for education, standardization, and buy-in.

Conclusion:
This study identified barriers and facilitators in launching an inpatient telestroke program within a health system, highlighting the importance of leveraging facilitators and addressing barriers for effective implementation and continuity.
Abstract WMP1: Neuroprotection by Normobaric Oxygen (NBO): Modulating Inflammasome (NLRP3) Activation and Stress Granule Formation in Ischemic Stroke
Authors: Guo Sichao , Geng Xiaokun , Li Fengwu , Ding Yuchuan
Published: February 2024

Background:
NBO has emerged as a promising neuroprotective strategy for ischemic stroke. Key to comprehending these effects is understanding its mechanisms. This study examines the pivotal roles of HIF-1α as an oxygen sensor, the protective emergence of stress granules (SGs) in response to various stimuli, and the inflammatory cell death process known as pyroptosis, triggered by inflammasomes. We elucidated the interplay between HIF-1α, SGs, inflammasomes in ischemia/reperfusion injury and in NBO-induced neuroprotection.

Methods:
A total of 132 adult male SD rats were subjected to 2 h middle cerebral artery occlusion (MCAO), followed by 2, 6, 24 or 48 h of reperfusion. At the onset of reperfusion, oxygen was inhaled for 2 h at concentration of 95% and flow rate of 2 L/min. YC-1 (HIF-1α inhibitor) was administered 2 h before MCAO. Brain damage was evaluated by infarct volumes (TTC), LDH and ROS levels (ELISA), apoptotic cell death (flow cytometry and TUNEL). Pyroptosis was evaluated by flow cytometry. mRNA and protein levels of HIF-1α and inflammasome related factors, including IL-18, IL-1β, ASC, NLRP3, TXNIP, N-GSDMD, cleaved-Caspase-1, as well as SGs proteins including DDX3X, G3BP1, TIA-1 were examined. Co-IP was used to detect the interaction between DDX3X and G3BP1, as well as DDX3X and NLRP3.

Results:
Infarct volumes, LDH and ROS levels, apoptotic and pyroptotic cell death, as well as HIF-1α expression were all increased after ischemia/reperfusion. All these increases were reversed by either NBO or YC-1. NBO or YC-1 further reversed the increase in expression of NLRP3 inflammasome related proteins and suppressed the interaction between DDX3X and NLRP3, thereby suppressing inflammasome activation. NBO or YC-1 stimulated the expressions of SGs proteins and facilitated the interaction between DDX3X and G3BP1, thereby promoting the formation of SGs, in association with cell protection.

Conclusion:
Our findings highlight the neuroprotective effects of NBO in ischemic stroke. This protection is attributed to its dual capacity to inhibit NLRP3 inflammasome activation while simultaneously promoting formation of SGs. Central to these processes, HIF-1α, as an instrumental modulator, sheds light on potential therapeutic targets for stroke intervention.
Abstract WMP112: Neutrophil Extracellular Traps Occlude the Cerebrovasculature Causing Delayed Cerebral Ischemia After Subarachnoid Hemorrhage in Mice
Authors: Zeineddine Hussein , Hong Sungha , Dienel Ari , Bernal Angelica , Torres Kiara , Thomas Sithara , Thankamani Pandit Peeyush , Blackburn Spiros , McBride Devin
Published: February 2024

Neutrophils are reported to be critical mediators of to poor outcome after subarachnoid hemorrhage (SAH). Following ischemic stroke, neutrophils cause vascular occlusion via neutrophil extracellular traps (NETs). In this study, our hypothesis was that NETs cause vascular occlusion leading to delayed cerebral ischemia (DCI) and worse outcome after SAH. SAH mice (male and female, young and aged) were administered one of the following: a neutrophil depleting antibody, a PAD4 inhibitor (to prevent NETosis), DNAse-I (to degrade NETs), or a vehicle (control). Mice had neurological assessment daily until day 7 and then were euthanized to quantify the amount of brain vascular NETs. Various subcohorts of mice were used to assess neutrophil propensity to NETose,
in vivo
formation of NETs via intravital microscopy, and MRI assessment of cerebral perfusion and infarct development. We also examined if NETs were present after SAH in 128 humans by measuring NETs markers via ELISA at 1, 2, 4, 7, and 10 days post-SAH. In mice, SAH induced a pro-NETosis phenotype selectively in skull neutrophils and caused intravascular NETs to be present by day 1 which persisted until at least day 7. Neutrophil depletion reduced NETs, improved cerebral perfusion and neurological outcome, and attenuated the incidence of DCI. Similar findings were observed for PAD4 inhibition. However, degrading NETs only marginally improved outcomes. Aneurysmal SAH patients who developed DCI had elevated markers of NETs compared to non-DCI patients. In conclusion, after SAH, skull-derived neutrophils are primed for NETosis, and neutrophils and NETosis are therapeutic targets to reduce DCI by preventing vascular occlusion by NETs.
Abstract WMP118: Utilizing Patient-Derived Induced Pluripotent Stem Cells as a Cellular Model for Studying Moyamoya Disease
Authors: Chiang Terrance , Tokairin Kikutaro , Demirag Zeynep , Rao Shailaja , Pendharkar Arjun , Cheng Michelle Y , Steinberg Gary
Published: February 2024

Introduction:
Moyamoya disease (MMD) is a rare cerebrovascular disease that can lead to stroke. A histopathological characteristic in MMD is the thickening of the intimal layer that causes narrowing of the vessel, suggesting dysfunctions in the vascular smooth muscle cells (VSMCs) and endothelial cells (ECs). The mechanism of MMD is largely unknown, due to a lack of established MMD-specific cellular or animal models. In this study, we established patient-derived cellular co-culture models using MMD iPSC-derived ECs and VSMCs. We also generated a 3D vascular organoid model to more closely mimic the MMD vasculature and function.

Methods:
Peripheral blood mononuclear cells (PBMCs) from MMD patients or healthy controls were used to generate iPSCs (n=4 per group). Differentiated ECs and VSMCs were validated and their functional characteristics were investigated in single and co-cultures. For co-cultures, ECs and VSMCs were labeled with Vibrant cell labeling dyes (DiO and DiD), followed by either transwell migration assay (ECs on bottom of cell culture plate and VSMCs on top Transwell insert) or in vitro angiogenic tube formation assay. Control and MMD iPSCs were used to generate 3D cellular organoids, and their cellular characteristics were examined using immunohistochemistry with antibodies labeling ECs and VSMCs.

Results:
While single cultures of ECs displayed similar tube formation patterns between control and MMD, co-cultures of ECs with VSMCs showed that MMD ECs failed to stabilize in vitro angiogenic tubes and formed aggregates at 24hr, when compared to control ECs. Transwell migration assays showed MMD VSMCs migrated faster than control VSMCs. Immunostaining of organoids with EC and VSMC markers showed notable differences in cellular composition, with MMD organoid showing compromised integrity of vascular networks, when compared with controls.

Conclusions:
We have established 3D organoid cellular models and in vitro co-cultures using MMD patient-derived iPSCs. Our co-culture studies revealed functional impairment in MMD EC/VSMC and organoid models revealed distinct characteristics in their vascular networks, possibly contributing to MMD pathology. These results shed useful insight into the cellular and molecular mechanisms driving MMD.
Abstract WMP13: The Modifying Effects of Psychosocial Health on the Association Between Cerebrovascular Health and Dementia Risk: The Atherosclerosis Risk in Communities (ARIC) Neurocognitive Study
Authors: Eswaran Surabhee , Gottesman Rebecca F , Kucharska-Newton Anna M , Koton Silvia , Liu Albert C , Liu Chelsea , Lutsey Pamela L , Mosley Thomas H , Palta Priya , Sharrett A R , Sullivan Kevin J , Walker Keenan , Groechel Renee C
Published: February 2024

Introduction:
Associations between magnetic resonance imaging (MRI) markers of vascular pathology and dementia risk in older adults have been established, but it remains less clear how lifestyle factors may modify this association. We hypothesized that a weaker association between MRI markers of vascular pathology and incident dementia will be present among older adults with
strong
as compared to
poor
psychosocial health in mid-life.

Methods:
Social support and social isolation were assessed among ARIC participants, aged 46 - 68, via self-reported questionnaires (1990 - 1992). Following categorization of both factors, participants were classified as having strong or poor mid-life psychosocial health. From 2011 - 2013, 1977 participants, aged 67 - 90, underwent 3T brain MRI quantifying white matter hyperintensity (WMH) volume, subcortical cerebral microbleeds (sCMB), infarcts, and white matter integrity through diffusion tensor imaging. Incident dementia cases were identified from time of imaging through December 31, 2019 (median follow-up: 6.4 years) with ongoing surveillance. Relative contributions of psychosocial health and MRI markers to incident dementia were evaluated with demographic and vascular risk factor-adjusted Cox-proportional hazard regression models.

Results:
Among 1612 dementia-free participants with measures of psychosocial health, MRI markers were associated with dementia risk in the hypothesized direction. Mid-life psychosocial health significantly modified the associations between sCMB and WMH, each, with incident dementia risk (Table 1; greater risk of dementia shown in individuals with poor psychosocial health).

Conclusions:
The elevated risk of dementia associated with sCMB and WMH is reduced in participants with strong psychosocial health in mid-life. Future studies evaluating social factors through the life course and the mechanisms by which they modify the relationship between pathology and dementia are needed.
Abstract WMP18: A Brain Care Score for Dementia and Stroke: Data From the UK Biobank Cohort
Authors: Singh Sanjula D , Oreskovic Tin , Carr Sinclair , Papier Keren , Conroy Megan , Senff Jasper , Chemali Zeina , Gutierrez-Martinez Leidys , Parodi Livia , Mayerhofer Ernst , Marini Sandro , Nunley Courtney , Kourkoulis Christina , Newhouse Amy , Ouyang An , Brouwers H B , Westover Brandon , Rivier Cyprien , Falcone Guido J , Howard Virginia J , Howard George , Sheth Kevin N , Yechoor Nirupama , Lazar Ronald M , Anderson Christopher D , Tanzi Rudolph , Fricchione Gregory , Littlejohns Thomas , Rosand Jonathan
Published: February 2024

Background:
The Brain Care Score (BCS) was developed through a modified Delphi process with practitioners and patients for implementation into primary care to stimulate behavioral changes and lifestyle choices to sustainably reduce the incidence of dementia and stroke (
Fig 1)
.

Methods:
To assess its validity as associated with incidence of dementia and stroke, the BCS was derived from the UK Biobank (UKB) baseline evaluation (2006-2010) for participants aged 40-69. Cox proportional hazards regression were used to estimate associations between the BCS and incident dementia and stroke, adjusted for sex, and stratified by age groups at baseline.

Findings:
The BCS (median: 12; IQR:11-14) was calculated for 398,990 UKB participants (mean age: 57; females: 54%). There were 5,354 incidents of dementia and 7,259 incidents of stroke during a median follow-up of 12.5 years. On average, a 5-point increase in baseline BCS was associated with a substantial significant decrease in dementia incidence (for those aged <50 years: HR: 0.41 [95%CI: 0.28-0.60], aged 50-59: HR: 0.68 [95%CI: 0.58-0.80], and aged >59 (HR: 0.92 [95%CI: 0.86-0.98]) as well as stroke incidence (for those aged <50 years: HR: 0.52 [95%CI: 0.44-0.61], aged 50-59: HR: 0.48 [95%CI: 0.44-0.53], and aged >59: HR: 0.67 [95%CI: 0.63-0.71])
(Fig 2).

Interpretation:
The BCS at baseline is strongly associated with risk of dementia and stroke in the UKB. Future research should include investigating the adaptability and implementation of the BCS for patients and providers into routine care worldwide.
Abstract WMP2: A Randomized, Double-Blind, Placebo-Controlled, Phase II Trial in Acute Non-Cardioembolic Ischemic Stroke With Adrenomedullin
Authors: Yoshimoto Takeshi , Saito Satoshi , Omae Katsuhiro , Kita Toshihiro , Kitamura Kazuo , Fukuma Kazuki , Washida Kazuo , Abe Soichiro , Ishiyama Hiroyuki , Yamaguchi Eriko , Yamagami Hiroshi , Nagatsuka Kazuyuki , Masahiro Tsuji , Minami Manabu , Yamamoto Haruko , Hattori Yorito , Tanaka Tomotaka , Ihara Masafumi
Published: February 2024

Background:
Adrenomedullin (AM), a vasoactive peptide, has strong anti-inflammatory and angiogenic properties, which have been reported to ameliorate the consequences of ischemic stroke (IS) in several animal models. This phase II clinical trial aimed to test the safety and tolerability of intravenous (IV) AM administration in acute IS (AIS) patients within 24 hours of onset.

Methods:
The AdrenoMedullin For Ischemic Stroke study is an investigator-initiated, randomized, double-blind, phase II trial. Patients with non-cardioembolic IS within 24 hours after stroke onset and baseline NIH Stroke Scale (NIHSS) score ≥1 were randomly allocated to the intermittent IV AM (I-AM group) (30 μg/kg in total for 7 days, n=20) or placebo group (n=10) in the first cohort and a combination of continuous (the first 3 days) and intermittent (the following 4 days) IV AM (C/I-AM group) (56 μg/kg in total for 7 days, n=20) or placebo group (n=10) in the second cohort. The primary endpoint was serious adverse events related to the protocol treatment and secondary efficacy endpoints were favorable outcomes (mRS 0-2 at 90 days) and good outcomes (mRS 0-3 at 90 days).

Results:
The population of 60 patients had a median age of 75 years, 21 patients (35%) were female, and the median NIHSS score was 3. The primary endpoint did not occur in all groups. In the secondary efficacy endpoints, the rates of favorable outcome (75.0% vs. 68.9%, adjusted odds ratio [aOR], 1.45; 95% confidential interval [CI], 0.32-6.53) and good outcome (90.0% vs. 73.7%, aOR 3.86; 95% CI, 0.67-22.11) in the I-AM group were not statistically different from those in the placebo group. The rates of good outcomes in the C/I-AM group were comparable with those in the placebo group (85.0% vs. 73.7%, aOR 1.56; 95% CI, 0.72-3.39).

Conclusions:
Treatment with IV AM within 24 hours of AIS onset is safe. Intermittent IV AM may contribute to improved AIS prognosis. The efficacy and safety of AM will need confirmation in the next phase of clinical trials.
Abstract WMP22: Higher Burden of Cerebral Small Vessel Disease is Associated With Risk of Incident Stroke in Community-Dwelling Individuals
Authors: Pinheiro Adlin , Demissie Serkalem , Aparicio Hugo J , Lioutas Vasileios , Beiser Alexa , Ekenze Oluchi , De Carli Charles , Seshadri Sudha , Romero Jose R
Published: February 2024

Background:
Mild manifestations of individual cerebral small vessel disease (CSVD) markers are common and may not denote increased risk, but high CSVD burden identifies individuals at increased risk of stroke and dementia. Scores incorporating multiple CSVD markers may better identify a person’s risk, but it remains unclear if they offer benefit beyond tools based on clinical factors alone such as the revised Framingham Stroke Risk Profile (FSRP). Therefore, we related a multi-marker CSVD score to risk of incident stroke and compared the findings with the FSRP in community-dwelling individuals.

Methods:
Framingham Heart Study (FHS) participants aged ≥55 years, free of stroke and dementia and with brain magnetic resonance imaging (MRI) ratings of CSVD markers were included. A multi-marker CSVD score reflecting increasing CSVD burden was used (one point each for presence of cerebral microbleeds, severe perivascular spaces, extensive white matter hyperintensities, covert brain infarcts, and cortical superficial siderosis, ranging 0-5). Multivariable Cox proportional hazards regression analyses were used to relate CSVD score to incident stroke.

Results:
Among 1,154 participants (46% male, mean age 70.9±8.7), 590 (51%) had score 0, 352 (31%) had score 1, 164 (14%) had score 2, and 48 (4%) had score ≥ 3. Over a median follow-up of 8.2 years (Q1-Q3: 5.1-12.5) from the time of MRI, 92 (8%) developed stroke. In models adjusting for time interval between clinic exam and MRI, FHS cohort, and FSRP score, number of CSVD manifestations was associated with increased risk of stroke in a dose-dependent manner: score 1 (HR: 1.73; 95% CI 1.05-2.84), score 2 (HR 1.83; 95% CI: 1.01-3.30), and score ≥ 3 (HR: 3.31; 95% CI: 1.50-7.28) in relation to participants with no CSVD markers. In comparison, a 5-percent increase in FSRP alone was associated with increased risk of stroke (HR: 1.25; 95% CI 1.15-1.36).

Interpretation:
Higher CSVD burden is associated with increased risk of stroke, beyond the effect explained by risk factors in the FSRP. These findings support consideration of CSVD burden to identify risk of stroke in community-dwelling individuals.