bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract TP307: Circulating immune cell landscape in ischemic stroke patients with early neurological deterioration
Authors: Liu Hongbing , XU YUMING , Gao Yuan
Published: January 2025

Introduction:
In this study, we investigated peripheral blood mononuclear cells (PBMCs) transcriptomics of patients who had a stroke using single-cell RNA sequencing (scRNA-seq) to understand peripheral immune response after Early neurological deterioration (END) based on the gene expression in an unbiased way.

Methods:
Transcriptomes of PBMCs from 5 patients who had END within 24 hours after stroke onset were compared with 5 race-matched/age- matched/gender-matched controls. Based on whether the patient experienced END and the timing before and after the occurrence of END, the samples were divided into four groups: END_T0, END_T1, Non-END_T0, and Non-END_T1.

Results:
A total of 20 peripheral blood PBMC samples were collected from patients with acute ischemic stroke before and after the occurrence of END. Compared with Non-END, the proportion of mononuclear macrophages in the peripheral blood of patients with END and the number of differential genes have significantly increased (
P
< 0.05). Further heterogeneity analysis of mononuclear macrophages revealed a cell subset C1Q
+
Mono that highly expresses C1QA. The proportion of this subset significantly increased before and after the occurrence of END (
P
< 0.05). Pseudotime analysis showed that its differentiation trajectory is different from that of classical mononuclear macrophages, and functional enrichment suggests it is related to the activation of inflammatory cells and the coagulation system.

Conclusion:
For the first time, our study constructed a peripheral blood immune landscape of acute ischemic stroke before and after the occurrence of END, as well as in Non-END cases, based on scRNA-seq. our study also identified a novel monocyte subpopulation, providing new insights into the immune regulation of END
Abstract TP312: Retrospective Analysis of Perioperative Stroke in Patients with Glioma
Authors: Bou Dargham Tarek , Ryan Dylan , Hassani Sara , Broadwater Gloria , Peters Katherine , El Husseini Nada
Published: January 2025

Background/Objectives:
Perioperative stroke is a significant cause of morbidity and mortality in patients undergoing cardiac, vascular, and neurosurgical procedures. We assessed the rate, characteristics, risk factors and survival outcomes of perioperative stroke following surgical resection of glioma.

Design:
This is a retrospective chart review of a single quaternary care center of patients with glioma between 2005-2021 who underwent resection. Stroke within 30 days of surgical resection was identified based on the radiology read of MRI brain for ischemic stroke and CT brain for hemorrhagic stroke that was obtained as part of clinical care. This was then confirmed retrospectively by a neurologist who reviewed imaging and medical records, excluding expected post-operative changes. Descriptive analysis and logistic regression were conducted. Overall survival was estimated with Kaplan-Meier methods from the date of surgery to death and compared with the log rank test.

Results:
Out of 738 patients who underwent surgical resection of their glioma and underwent brain MRI or CT head, 20 (2.71%) had radiographic evidence of strokes, with the mean (SD) time from surgery to stroke 5.4 (16.2) days. Of these, 13 (65%) had ischemic strokes, 7 (35%) had hemorrhagic strokes. Out of all perioperative strokes, 9 (45%) were symptomatic (total incidence of 1.2%), and 11 (55%) were asymptomatic. Patients who had a stroke were older [mean (SD); 60.4 (13.7) vs. 52.8 (15.0) years; p=0.026], had a higher rate of atrial fibrillation (p= 0.002), and had comorbid hyperlipidemia (p=0.039) and hypertension (p=0.047). Descriptive analysis of this cohort is summarized in Table 1. Older age, carrying a diagnosis of atrial fibrillation, and having hyperlipidemia were associated with higher odds of having a perioperative stroke (Table 2). In an attempt to generate a multivariate logistic model, stepwise selection yielded no significant results likely due to the low number of strokes in this cohort. The median survival for patients with stroke was 24.6 months (95% CI:21.8-32.1), which was lower than for patients who did not suffer a stroke (29.3 months, 95% CI: 25.6-32.9) (p=0.052).

Conclusion:
Older age, atrial fibrillation, hyperlipidemia, and hypertension were associated with perioperative stroke risk after glioma resection. Future studies should evaluate underlying mechanisms and stroke etiologies to better identify high risk patients.
Abstract TP333: Racial disparities in the management of newly diagnosed diabetes mellitus in Acute Ischemic Stroke
Authors: Bowers Jeffrey , Meyer Dawn , Banerjee Ananya , Geib Teneille , Angeles Theresa , Carrion Penagos Julian , Ravi Vikas , Pirahanchi Yasaman , Bavarsad Shahripour Reza , Modir Royya , Meyer Brett , Hemmen Thomas , Agrawal Kunal
Published: January 2025

Introduction:
Diabetes Mellitus (DM) is a significant risk factor for acute ischemic stroke (AIS) and the incidence of newly diagnosed DM in AIS is higher in certain ethnicities. We aim to examine prescribing patterns of anti-hyperglycemic medications (anti-DM) in hospitalized AIS patients with newly diagnosed with DM. We also examine ethnic disparities in prescribing patterns amongst Hispanic and Non-Hispanic patients.

Methods:
We retrospectively examined prospectively collected data from an IRB-approved stroke registry at two academic Comprehensive Stroke Centers (CSCs). We included patients with a new diagnosis of AIS with no documented history of DM between 1/1/2013 and 6/30/2024. We examined baseline demographics, comorbidities, ethnicity, insurance status, acute stroke treatment, NIHSS, A1c, blood glucose and their association with anti-DM prescribing patterns. We also evaluated prescribing differences in Hispanic versus Non-Hispanic groups. Data was analyzed using correlation matrix, Pearson’s and Spearman’s correlation coefficients, and Chi-squared and t test, as appropriate.

Results:
A total of 2870 AIS patients were identified in the study period. Of these, 20.1% (n=578) were Hispanic, 42.5% (n=1219) were female, and 47.8% (n=1373) had Medicare as their payment source. New diagnosis of DM occurred in 6.0% (n=52/863), and 52.0% (n=27) were prescribed anti-DM at discharge. Overall, only a history of previous stroke was independently associated with prescribing anti-DM on discharge (p=0.03). Of patients with new DM, Hgb A1c (p=0.01) and blood glucose (p=0.006) were significantly associated with prescribing anti-DM on discharge. Patients with Medicaid (p=0.04) and no previous medical history (p=0.02) were less likely to receive anti-DM. Mean Hgb A1c was higher in patients that were prescribed anti-DM vs not prescribed anti-DM (8.82 vs. 7.13; p=0.007, 95% CI: -2.87 to -0.52). There was no difference in prescribing anti-DM in Hispanic vs. Non-Hispanic groups.

Conclusions:
In this study at two academic CSCs, there was no significant difference in prescribing anti-DM medications in Hispanic vs. Non-Hispanic groups, but insurance status may be associated with prescribing patterns. The provision of systematic care helped reduce healthcare disparity in AIS patients with newly diagnosed DM.
Abstract TP334: Racial Disparities in Functional Outcomes and Stroke Recurrence in Young Patients with Ischemic Stroke
Authors: Peshwe Krithika , Li Ya-Huei , akram nida , Nouh Amre , Hou Yan
Published: January 2025

Introduction:
Studies have reported racial disparities in acute stroke treatment and follow-up care in young patients which lead to less desirable outcomes for minorities. This study aimed to identify potentially modifiable factors for better stroke treatment and prevention in minority populations.

Methods:
Young patients aged 18-50 years who were admitted with ischemic stroke during 09/2016-12/2022 were retrospectively identified and stratified as non-Hispanic White (WH), non-Hispanic Black (BL), and Hispanic (HS). Racial differences in risk factors, stroke etiology, acute intervention, and follow-ups were examined using Chi-square and Kruskal-Wallis tests as appropriate. Cumulative probabilities of stroke recurrence were estimated using the Kaplan-Meier (KM) method and tested with the Log-rank (Mantel-Cox) test. A logistic regression was used to evaluate the odds ratio of favorable functional outcomes (mRS ≤2) by 90 days. A backward stepwise Cox regression was conducted to identify predictors of stroke recurrence reported as hazard ratio (HR) and a 95% confidence interval (CI).

Results:
A total of 318 patients were identified with a median age of 43 and 57.5% male, covering 57.2% WH, 22.3% BL, and 20.4% HS. Compared to WH, more BL and HS were comorbid with diabetes, hypertension, and prior stroke (p<0.05). The rates of other risk factors did not vary by race. The distribution of stroke etiologies and rate of acute interventions (IV tPA, thrombectomy) were similar among the three. After discharge, 77.3% of young patients had ≥1 follow-ups at stroke clinic. The total number of stroke clinic follow-ups were similar among racial groups. At 90 days, 89.6% of patients achieved mRS≤2; the odds of having this favorable functional outcome were similar among racial groups (
p
=0.207). The KM curve indicates that the first-year risks of stroke recurrence were similar among racial groups and that a trend showed BL had the highest risk of recurrent strokes, followed by HS, and WH had the lowest risk in 1-3 year follow up. Yet, these differences were not statistically significant (
p
=0.056. BL was found to have 2.7 times higher risk to have a recurrent stroke than whites (HR: 3.7; 95% CI: 1.4-10.1; p=0.01).

Conclusions:
Findings highlighted high prevalence of hypertension and diabetes in young BL and HS and a higher risk of recurrent stroke in young BL, suggesting tailored interventions for comorbidities are urged for better stroke prevention in minorities.
Abstract TP337: Blocking insulin-like growth factor 1 receptor in the gut abrogates IGF-1 mediated long-term neuroprotection in middle-aged female rats
Authors: Bake Shameena , Pickle Kaylin , Kallo Mona , Bhatt Hetvi , Sohrabji Farida
Published: January 2025

Background and Purpose:
Our previous studies in a rat model of ischemic stroke identified that intraperitoneal (IP), but not intracerebroventricular (ICV) administration of IGF-1 reduced stroke-induced gut leakiness and peripheral inflammation in the acute phase and attenuated stroke-induced impairment in acyclic middle-aged female rats. These data suggest that the gut may be implicated in IGF-1-mediated effects on stroke-induced cognitive impairment. To directly assess whether the effect of IGF-1 on behavioral improvement is mediated by the gut, study utilized a novel tet-inducible rAAV construct to block IGF1R specifically in the gut.

Methods:
Female Sprague Dawley rats (9-11 mo) were intragastrically gavaged with either recombinant rAAV construct containing IGFR-shRNA (IGFR-sh) downstream of the IESC promoter Lgr5 in a Tet-inducible system or rAAV-empty vector (Scr-sh) 4 weeks prior to experimental ischemia. Animals were subjected to endothelin-1 induced MCAo. Doxycycline was administered 4h later and IGF-1 was given ip at 4 and 24 h post-stroke. Sensorimotor function as well as peripheral inflammation (in serum samples) was assessed at 5d post-stroke and long-term cognitive impairment was evaluated after 60 days.

Results:
The mCherry reporter in the rAAV construct was observed in the intestinal crypt, indicating appropriate delivery of the construct. Sensorimotor function evaluated by vibrissae evoked forelimb placement task was significantly impaired in the ipsilateral paw after stroke in IGFR-Sh+IGF-1 compared to Scr-sh+IGF-1(p<0.005). IL-17 levels in serum were significantly elevated in the animals with IGFR-Sh+IGF1 compared to Scr_sh+IGF1 (p<0.004). Cognitive impairment assessed by Barnes maze showed no differences in spatial learning but revealed significant impairment in spatial recall in IGFR-sh+IGF1 group compared to SCR-sh+IGF1 animals (p<0.02).

Conclusions:
The present findings indicate that the beneficial effects of IGF-1 on long-term stroke recovery may be partially mediated by its effects on the gut and implicate the inflammatory cytokine IL-17a as a modifier of stroke-induced cognitive impairment.

Supported by RF1NS119872 to FS and SB
Abstract TP344: Ketamine Modulates Astrocyte-Secreted Proteins to Promote Recovery in a Mouse Model of Stroke
Authors: Berghella Andrea , Pang Zibei , Blanco-Suarez Elena
Published: January 2025

Introduction:
Astrocytes are non-neuronal cells in the CNS that play crucial roles in synaptic formation, maturation, and maintenance through the synthesis and secretion of various proteins. We identified Chordin-like 1 (Chrdl1) as an astrocyte-secreted protein that limits synaptic plasticity by stabilizing GluA2-containing AMPA receptors (GluA2-AMPARs) at synaptic sites in the cortex. In a mouse model of ischemic stroke, we found that Chrdl1 is excessively upregulated in astrocytes in the peri-infarct area during the post-stroke plasticity window (2–30 days post-stroke in the mouse). We found that Chrdl1 KO mice displayed enhanced synaptic plasticity, and in response to stroke, deficits such as dendritic spine degeneration, impaired GluA2-AMPAR distribution, and motor dysfunction were significantly alleviated. Seeking a pharmacological approach to mitigate stroke-induced Chrdl1 upregulation, we explored the use of sub-anesthetic ketamine, known to enhance plasticity and alter astrocytic function, potentially affecting protein secretion. However, its impact on post-stroke astrocyte-regulated plasticity and recovery has not yet been explored.

We
hypothesize
that sub-anesthetic ketamine may restrict the upregulation of astrocytic Chrdl1 during the post-stroke plasticity window and reduce stroke-induced deficits.

Methods:
To generate ischemia
in vivo
, we used photothrombosis to induce distal middle cerebral artery occlusion (PT-dMCAO). Male and female adult mice (2 months old) received a daily dose of sub-anesthetic ketamine (10mg/kg) via intranasal injection for one week. We used single molecule fluorescence
in situ
hybridization (smFISH) and immunohistochemistry to assess Chrdl1 mRNA and protein levels in peri-infarct astrocytes, synaptic staining and high-resolution confocal microscopy to analyze GluA2-AMPARs distribution, Golgi stainings to study dendritic branching and spine density, and several behavioral tests to assess motor performance, sensorimotor function, and learning and memory.

Results:
We found that sub-anesthetic ketamine treatment reverts stroke-induced Chrdl1 upregulation in peri-infarct astrocytes and mitigates molecular, structural and behavioral deficits.

Conclusions:
Our study suggests that sub-anesthetic ketamine treatment is a promising approach to limit astrocyte-driven molecular deficits during the critical post-stroke plasticity window, which may otherwise hinder recovery, and holds great promise for clinical translation.
Abstract TP347: Sex differences of immunosuppression and phagocytosis after stroke as a correlative measure for post-stroke functional recovery
Authors: Mohapatra Swati , Banerjee Anik , Couture Lucy , Baskin Lynae , Lee Eunyoung , McCullough Louise , Ritzel Rodney
Published: January 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<0.05, n=7-11/grp) compared to men (ns, n=21-22/grp). Female presented a robust phagocytic capability and CHIT1 depression on peripheral monocytes (p<0.05, n=7-11/grp). This effect is not observed in men, who exhibit greater phagocytic capacity after 1 day after stroke (p<0.01, n=21-22/grp) measured by bead uptake assay using flow cytometry. Variations in CHIT1 levels in PBMCs correlated with stroke severity and infection risk, underscoring its potential role in sex-dependent outcomes.

Conclusion:
Our data suggests that peripheral reduction of CHIT1 levels impairs phagocytosis and increases susceptibility to infections as a risk factor for poorer stroke outcomes. CHIT1 appears to be a novel mediator of sex differences in post-stroke immune suppression. Targeting the anti-fungal response protein CHIT1 could help normalize phagocytic responses in older women, potentially reducing infection rates and improving post-stroke outcomes. Further research into CHIT1's interaction with pathogen-associated molecular patterns could provide new therapeutic strategies for stroke management.
Abstract TP351: Evidence of sustained monocytosis during chronic stroke recovery
Authors: Verma Rajkumar , DiMauro Sharon , Gamiotea Turro Daylin , Yadav Sanjeev , Mittal Sanjay , Zhou Beiyan , Liang Bruce
Published: January 2025

An acute ischemic stroke (AIS) triggers rapid mobilization of immune cells from bone marrow, leading to the infiltration of circulating immune cells into the brain. Among these immune cells, monocytes, which are pivotal in both adaptive and innate immune responses, play a crucial role in stroke injury and recovery in a temporal manner. Previous research indicates that tissue injury such as AIS causes acute monocytosis. However, it remains unclear if this upregulation persists during the recovery phase. Given the diverse roles of monocytes during post-stroke recovery, we hypothesize that their numbers remain elevated during chronic recovery.

In this study, we will analyze the effect of stroke duration on monocytosis and the factors affecting this process after AIS.

We recruited consecutive AIS patients (58-90 years) undergoing endovascular clot retrieval and age-matched healthy control subjects of both sexes, with informed consent obtained from all participants. Flow cytometric analysis of whole blood-derived immune cells, including monocytes, was performed at 0–2 days (acute, n=20), 3–7 days (subacute, n=20), and 65±20 days (chronic, n=14) after stroke onset. These were compared with healthy subjects (n=20 per age group). A pure monocyte population was isolated using a side and forward scatter plot with cell-surface markers, such as HLA-DR, CD45, CD11b, CD14, and CD16, along with a negative gating strategy. Plasma samples were analyzed for various secreted cytokine levels using the Millipore multiplex array. scRNA-seq analysis was employed to support the evidence of monocytosis using total immune cells of these subjects.

We found that the total monocyte count (% of total immune cells) progressively increased during recovery in AIS patients (P<0.05), which was corroborated by unbiased scRNA-seq analysis data. Cytokine analysis indicated that the levels of M-CSF and G-CSF also progressively increased, further supporting the evidence of monocytosis after stroke. Subclassification of monocyte clusters from RNA-seq data suggested that specific monocyte subsets are the major contributors to monocytosis.

In summary, our data support the evidence of continued monocytosis after ischemic stroke, indicating diverse roles for monocytes beyond the acute inflammatory response. Detailed molecular characterization of monocytes, their subpopulations, and their genetic composition over time may provide novel insights into their pathophysiological roles during stroke recovery.
Abstract TP358: Stroke Exacerbates Respiratory Function and Cognition in Mice with Dementia
Authors: Zhang Yuxing , El Hamamy Ahmad , IQBAL ZAHID , Ranjan Arya , Sumani Destiny , McCullough Louise , Li Jun
Published: January 2025

Introduction:
Stroke is a well-established independent risk factor for the development of dementia. Most dementia patients exhibit mixed brain pathologies, with histological evidence of ischemia and Aβ plaque accumulation, observed at autopsy. It is known that apnea/breathing disorders are independent risk factors for cognitive dysfunction and the progression of dementia. Our previous work suggested stroke impairs breathing control in wildtype mice. Here we hypothesize that, in mice with pre-existing dementia, stroke will exacerbate their respiratory dysfunction and further impair cognitive function.

Methods:
We used Tg-SwDI mice as a model for cerebral amyloid angiopathy (CAA), a major type of dementia. Female (11 to 13 months old) Tg-SwDI mice underwent pd-MCAO (permanent distal middle cerebral artery occlusion surgery) with age and sex matched wildtype and sham controls. Barnes Maze and Novel Object Recognize Test (NORT) were used for cognitive assessment, while whole-body plethysmography captured respiratory metrics, including apnea rate at 6 weeks post-surgery. All data are presented as Mean±SEM.

Results:
Tg-SwDI mice without stroke showed significant increases in apnea rates (per min) compared to the wide-type mice without stroke (5.8±0.26 vs. 1.04±0.11,
p
=0.0003, n=7 and 5) and displayed worsen performance in Barnes Maze (escape latency 59.5±11.6 vs. 23.7±6.1,
p
=0.044, n=7 and 5) and NORT (percentage time spent with novel object 42.0±5.8% vs. 61.9±6.2%,
p
=0.019, n=7 and 5). pd-MCAO increased apnea events in Tg-SwDI group (9.5±0.91 vs. 5.8±0.26,
p
=0.0009, n=9 and 7) vs. Tg-SwDI mice without stroke. Tg-SwDI mice with pd-MCAO exhibited worsen performance in Barnes Maze escape latencies (93.7±10.4 vs. 59.5±11.6,
p
=0.027, n=9 and 7) compared with Tg-SwDI mice without stroke. There was also a non-significant reduced novel object interaction time in NORT (36.8%±3.54 vs. 42.0%±5.8,
p
=0.43, n=9 and 7).

Conclusions:
Stroke worsens both respiratory dysfunction and cognitive memory impairment in CAA mice. The increased breathing disorder may be a contributing factor for worsened cognition in CAA mice.
Abstract TP375: Ischemic Insult Under Hyperhomocysteinemic Condition Triggers Early Onset Of Inflammatory Response Causing Exacerbation Of Brain Injury
Authors: Deep Satyanarayan , Seelig Sarah , Gomez Madelyn , Paul Surojit , Poddar Ranjana
Published: January 2025

Hyperhomocysteinemia, a metabolic disorder characterized by systemic elevation of amino acid homocysteine, is linked to deficiency in vitamins and enzymes involved in homocysteine metabolism. The incidence of hyperhomocysteinemia is high in the elderly population due to reduced micronutrient absorption and metabolism. Recent preclinical studies in animal models of stroke showed that predisposition to hyperhomocysteinemia exacerbates ischemic brain injury and worsens behavioral deficits, establishing hyperhomocysteinemia as a potential comorbidity for stroke. These studies further showed that hyperhomocysteinemia-induced stimulation of GluN2A subunit containing NMDA receptors (GluN2A-NMDARs) in conjunction with glutamate-induced stimulation of GluN2B subunit containing NMDARs (GluN2B-NMDARs) exacerbates stroke pathology. However, the precise intracellular mechanisms involved in such exacerbation of ischemic brain injury is not known. The current study sought to investigate whether under hyperhomocysteinemic condition GluN2A-NMDAR mediated early activation of the transcription factor Nuclear Factor-κB (NFκB) and subsequent expression of the pro-inflammatory chemokine Monocyte chemoattractant protein-1 (MCP-1) enhances post-ischemic inflammatory response and exacerbation of brain damage.

Adult male Wistar rats were made hyperhomocysteinemic by implantation of Alzet osmotic pumps containing L-homocysteine. The animals were hyperhomocysteinemic within 3 days with a total plasma homocysteine level of ~24 μM. Acute ischemic stroke was induced by middle cerebral artery occlusion for 60 min followed by reperfusion (6h). Brain tissues were processed for MCP-1 ELISA and RT-PCR. A significant increase in MCP-1 mRNA and protein levels were observed in the ipsilateral cortex of hyperhomocysteinemic rats compared to control rats within 6h of reperfusion. An accelerated brain damage was also observed at this time in the hyperhomocysteinemic rats. Inhibition of GluN2A-NMDAR (NVP-AAM077, i.v.) and NFκB (BMS345541, IKK inhibitor; i.p) at the onset of ischemic insult attenuated increase in MCP-1 mRNA and protein levels, as well as exacerbation of brain injury under hyperhomocysteinemic condition. The study provides compelling evidence for a novel role of GluN2A-NMDAR in promoting neuro-inflammatory response that contributes to exacerbation of stroke pathology under hyperhomocysteinemic condition.
Abstract TP381: Alterations in Heart Rate Variability After Ischemic Stroke in Rats: Heart-Brain Connectivity
Authors: Alavi Rashid , Dai Wangde , Li Jiajun , Carreno Juan , Pahlevan Niema , Arakaki Xianghong , Gharib Morteza , Kloner Robert
Published: January 2025

Introduction:
Heart rate variability (HRV), which represents fluctuations in heart rate, provides critical insights into autonomic regulation and cardiovascular function. This study aims to evaluate how HRV metrics change before, during, and after an ischemic stroke in a rat model, with a focus on understanding the impact of stroke and subsequent reperfusion on autonomic control.

Methods:
We employed the standard intraluminal suture middle cerebral artery (MCA) occlusion model to induce ischemic stroke in anesthetized adult male and female Sprague Dawley rats (n=11, 2-3 months old, average body weight: 296 ± 47 g, 27% female). The procedure involved temporary occlusion of the common carotid artery (CCA) while advancing a suture into the internal carotid artery to occlude the MCA for 1 hour, followed by 3 hours of reperfusion (Fig. 1). Electrocardiogram (ECG) signals were continuously recorded throughout the procedure. Post-surgery, cerebral infarction was confirmed via the triphenyl tetrazolium chloride (TTC) staining technique. HRV metrics were analyzed from 1-minute ECG recordings taken at three time points: baseline, 1 hour post-MCA occlusion (pre-reperfusion), and 3 hours post-reperfusion.

Results and Conclusions:
Significant alterations in HRV metrics were observed between baseline and 3 hours after reperfusion (p<0.05; Fig. 2; see figure’s caption for the metric descriptions). Specifically, high-frequency relative power percentage (HF%) and the SD1/SD2 ratio decreased significantly, while low-frequency relative power percentage (LF%) and the LF/HF ratio increased significantly. Additionally, the LF/HF power ratio showed a notable increase from baseline to 1 hour post-MCA occlusion. Our findings reveal distinct HRV metric changes associated with the ischemic stroke. The observed alterations reflect a shift of autonomic regulation towards sympathetic dominance, which intensifies after reperfusion, supporting other preclinical and clinical findings. These results suggest the potential for developing non-invasive, HRV-based techniques for real-time detection and monitoring of ischemic stroke. Further research could enhance these techniques' applicability in clinical settings.
Abstract WMP22: Magnetic Resonance Imaging Markers of Brain Health to Assess Functional Outcome After Acute Ischemic Stroke: a Quantitative Comparison Study
Authors: Lindgren Erik , Angeleri Luca , Bonkhoff Anna , Regenhardt Robert , Rost Natalia , Schirmer Markus
Published: January 2025

Introduction:
Brain health facilitates resilience to withstand detrimental effects of neurological diseases. Magnetic resonance imaging markers that quantify brain health may hence improve clinical modeling of functional outcome after acute ischemic stroke (AIS). Here, we aimed to compare the modeling performance of four quantitative brain health measures in a large, multicenter clinical setting.

Methods:
We analyzed 2,223 adult AIS survivors from the MRI-GENIE study, an international multicenter cohort (17 centers; 2003 - 2011) with acute T2-FLAIR imaging. We used dedicated deep learning enabled automated pipelines to assess white matter hyperintensity volume (WMHv), brain volume, and intracranial volume (ICV). We assessed the following brain health markers: 1) Brain Parenchymal Fraction (BPF, defined as brain volume relative to ICV), 2) Brain Age (BA, estimated using radiomics in an ElasticNet linear regression model), 3) Brain Reserve (BR, defined as normal appearing brain volume relative to ICV), and 4) effective Reserve (eR, defined as a latent variable calculated through structural equation modeling based on age, WMH load and brain volume with coefficients estimated in an independent cohort). We evaluated the brain health markers in separate logistic regression models of poor outcome (modified Rankin Scale score 3-5 at 90 days) adjusting for sex, diabetes type 2, hypertension, stroke severity (NIHSS), and age, brain volume and WMH load if not used to determine the respective brain health measure (see Table 2). Models were compared in terms of goodness of fit using Bayesian Information Criterion (BIC).

Results:
Of 2,223 patients with complete data (median age 67 years, 45% female), median NIHSS at admission was 3, and 24% of patients had poor outcomes (see Table 1). The model utilizing eR (BIC=2171.8), showed the lowest BIC values, providing moderate statistical evidence to outperform the BA model (BIC=2175.7, ΔBIC > 2), and very strong (ΔBIC > 10) statistical evidence to outperform all other models (see Table 2).

Conclusions:
In conclusion, incorporating eR as a quantitative measure of brain health, determined from routinely acquired clinical imaging, has the potential to improve personalized patient prognostication and modeling of functional outcome after AIS.
Abstract WMP33: Optimizing public acute stroke care in developing regions: a strategic resource allocation analysis for Sao Paulo State, Brazil
Authors: Alessio-Alves Frederico , Camilo Millene , Liso Elisabete , Pontes-Neto Octavio
Published: January 2025

Introduction:
Acute stroke care (ASC) is crucial to improve patient outcomes. In developing regions, optimizing resources is essential to enhance effectiveness of stroke careline networks. Sao Paulo State presents a unique challenge due to its territory and healthcare infrastructure. This study aims to analyze current and potential territorial coverage for expanding ASC.

Hypothesis:
We hypothesize that by systematically analyzing existing resources, mapping and designing 30-60 minutes isochrones, it is possible to identify catchment gaps in the system. This analysis could guide strategic expansions and adaptations to enhance ASC coverage.

Methods:
We conducted a comprehensive analysis of current public healthcare infrastructure across Sao Paulo State, focusing on essential resources for ASC - 24/7 CT scan, ICU, ERs with local or remote neurologist support. Geographic Information System technology was employed to create isochrones reflecting the accessibility of healthcare facilities within 30-60 minutes. We also considered the implementation of telemedicine, to expand coverage in underserved areas.

Results:
Our analysis revealed significant disparities in the availability of current stroke care resources across Sao Paulo State, with 150 beds on 23 stroke units currently operating. This finding represents a massive discrepancy from the estimated 900 stroke unit beds recommended in the state based upon Brazilian stroke careline ministerial ordinance that estimates 5 stroke beds per 200 stroke admission annually. Urban areas demonstrated heterogeneous coverage depending on the regional health department division, while rural and remote regions showed critical gaps, with limited access to 24/7 CT scans, neurological support, and ICU beds. The isochrone maps highlighted regions where the existing infrastructure (figure 1) could be optimized to improve coverage (figure 2). Potential adaptations, such as the deployment of telemedicine and strategic placement of stroke units, were identified as feasible solutions to bridge these gaps.

Conclusions:
The findings emphasize the importance of a targeted approach to expand ASC coverage in developing regions. By leveraging available resources and strategically implementing new technologies, Sao Paulo State can significantly improve its ASC network. This analysis provides a model that can be adapted for other regions facing similar challenges, ultimately contributing to better stroke outcomes in developing countries.
Abstract WP329: Causal Association of Left Atrial Emptying Fraction With Ischemic Stroke: A Mendelian Randomization Analysis
Authors: Nguyen Kevin , Cole John , Perry James , Gaynor Brady , Bai Zilong , Wang Fei , Xu Huichun , Leifer Dana
Published: January 2025

Introduction:
Atrial cardiomyopathy (AC) is associated with ischemic stroke (IS) in the absence of known atrial fibrillation (AF), but it is not known if AC is causally linked to IS. We are using Mendelian randomization (MR) to study whether AC traits are causally linked to IS.

Methods:
We used genetic variants associated with atrial traits by GWAS as proxies for traits defined by cardiac MRI (left atrial (LA) minimum and maximum volumes and active, passive and total emptying fractions (LAAEF, LAPEF, LATEF)) and by EKG (PQ interval). Linkage of these variants with IS and with TOAST stroke subtypes was studied in IS cases and controls from the NINDS Stroke Genetics Network and Early Onset Stroke Consortium. Causal estimates were calculated using MR Inverse-Variance Weighted (IVW), MR-Egger, and median methods. Imaging-derived atrial traits were highly correlated with each other, but were minimally correlated with EKG-derived atrial traits (PQ Interval). Therefore, we set p value cutoff at 0.05/2=0.025 to claim statistical significance.

Results:
MR analysis using genetic variants passing genome-wide significance showed that decreased LATEF was causally associated with the risk of IS (IVW p=0.008), which appeared to be primarily driven by the risk of cardioembolic stroke (IVW p=0.028). Decreased LAAEF was causally associated with IS (MR-Egger p=0.003) and stroke of undetermined etiology (MR-Egger p=0.003). MR using variants with genome-wide significance did not find causal associations for the other traits with IS or its subtypes.

Conclusion:
The MR analysis suggests that left atrial dysfunction may be causally associated with an increased risk of ischemic stroke. Notably, reduced LATEF appears to primarily elevate the risk of cardioembolic stroke, while decreased LAAEF is associated particularly with strokes of undetermined etiology. Additional analysis will be conducted to examine whether atrial fibrillation mediates the causal connections between these atrial traits and stroke. These findings underscore the importance of atrial health as a potential target in stroke prevention.
Abstract WP38: Spatial Transcriptomics of Remodeling Brain Arteries Reveals Potential Molecular Signals for Dystrophic Versus Eutrophic Responses to Flow
Authors: Poppenberg Kerry , Kolega John , Veeturi Sricharan , Siddiqui Adnan , Tutino Vincent
Published: January 2025

Introduction:
Biomarkers combining blood-based gene expression and image-based features are an emerging method to detect and stratify intracranial aneurysms (IAs). However, the relationship between vascular hemodynamic insult and aneurysm initiation growth is poorly understood. Here, we sought to use local gene expression levels from spatial sequencing of IA tissue to study this complex interaction.

Methods:
We performed bilateral carotid artery ligation on a New Zealand white rabbit to increase blood flow, inducing hemodynamic insult at the basilar terminus (BT). We euthanized the rabbit 24 hours post-surgery. We reconstructed the basilar artery (BA) using 3D angiography images and performed computational fluid dynamics (CFD) to compute pressure and wall shear stress (WSS), gradient (WSSG), and divergence (WSSD). 10-micron frozen sections of BA and BT in the plane of the bifurcation were collected onto Visium Spatial Gene Expression Capture Slide. Illumina sequencing libraries were constructed with unique molecular identifiers (UMI) and reads were aligned to rabbit genome. UMI counts were quantified for each spot using Cell Ranger pipeline. Using histological images and Loupe Browser, we identified spots on intima and media. Considering only genes with expression in greater than or equal to 50% of samples, differentially expressed genes (DEGs) were identified by F-test (p<0.1).

Results:
Using CFD, we observed a significant change in WSS along the BA and BT and changes in pressure, WSSG, and WSSD. A representative plot of WSS and WSSD along BT is shown in Fig. 1. When comparing BA to BT, we identified 215 DEGs in media and 155 in intima. DEGs largely reflected organismal injury/abnormalities and tissue development. Violin plots illustrate summarized expression of DEGs across groups of interest.

Conclusion:
WSS on BT increased ~4x after ligation. Expression analysis from spatial sequencing revealed ample differential expression between BA and BT for both intima and media.
Abstract WP91: Which patients with acute ischaemic strokes requiring reperfusion therapy present without ambulance transport?
Authors: Bacchi Stephen , Goh Rudy , El-Masri Shaddy , Sorby-Adams Annabel , Farnan Ava , Kimberly W. Taylor , Willcourt Matthew , Moey Andrew , Kleinig Timothy , Jannes Jim
Published: January 2025

Introduction:
Education campaigns have previously successfully informed the public regarding stroke symptoms and the need for urgent evaluation of suspected stroke. However, not all patients with strokes requiring intervention present to the hospital by ambulance, which would usually be the fastest means by which to reach a hospital. The aims of this study were to characterize the cohort of patients with an acute ischemic stroke that require reperfusion therapy who present to an emergency department without engaging ambulance services.

Methods:
A multicentre statewide retrospective cohort study was conducted involving all acute ischemic stroke admissions in South Australia from January 1, 2018, to January 1, 2024. Data were analyzed for all patients who received reperfusion therapy (either thrombolysis or endovascular thrombectomy) and presented directly to hospital (interhospital transfers and remote retrievals were excluded) via either ambulance or a non-ambulance (walk-in or driven by other) method.

Results:
Of the 1,497 individuals who presented directly to hospital and 66.1% received thrombolysis and 53.6% received endovascular thrombectomy, 60/1,497 (4.0%) presented without an ambulance (10 cases per year in a state with a population of 1.8 million). Those who received reperfusion therapy after presenting without an ambulance were more likely to be male (75.0% vs 56.0%, P < 0.001) and younger (median 65.4 vs 75.5 years, P < 0.001) than other patients who received reperfusion. Those who presented without an ambulance had longer door-to-scan (median 24 vs 34 minutes, P < 0.001) and door-to-needle times (median 63 minutes vs 70 minutes, P = 0.18).

Conclusion:
Reperfusion-eligible stroke patients not utilising ambulance services are more likely to be young and male. Patients receiving reperfusion therapy after presenting without an ambulance are uncommon, but such cases demonstrate the ongoing need for educating specific patient populations about the importance of identifying new stroke symptoms and seeking urgent evaluation and hospital transport. Further research is needed to elucidate the underlying causes, and design education strategies to reinforce the need to urgent emergency service contact.
Abstract WP96: Historical Redlined Communities Overlap with High Mobile Stroke Call Density-A Geospatial Analysis
Authors: Vora Shivam , Hake Joshua , Willis Corbin , hall maelee , Jennings Nate , Katz Brian , Rai Vivek , Loochtan Aaron , Hicks William , crow daniel
Published: January 2025

Background:
We sought to find a relationship between historically redlined communities and mobile stroke unit (MSU) call density using geospatial software.

Methods:
The Mobile Stroke Treatment Unit of metropolitan Columbus, Ohio, provides emergency stroke care coverage for 325 square miles spanning 47 zip codes. Our MSU is operational from 0700-1900 and is dispatched for all 911 calls designated as probable or definite strokes. We retrospectively reviewed all MSU calls from June 2019 to December 2023. and included all confirmed stroke patients in this analysis. Each call address was geocoded and entered into the ESRI/ArcGIS Online geospatial analysis software. Call addresses were then clustered into hexagonal grids with a distance band of 1 km for hotspot analysis. Statistically significant hotspots were qualitatively defined as clustered grids with high activity and quantitatively defined as having a Gi Bin score > 2, which correlates to statistical confidence > 95%. The hotspots were then overlaid upon an ESRI/ArcGIS pre-loaded historical map of redlined communities in Columbus, Ohio.

Results:
We received 7442 calls during our study period. Of these calls, 738 were accurately diagnosed as a stroke. Our hotspot analysis identified 9 hexagonal grids as statistical hot spots. Disadvantaged communities in the historical redlined map are depicted as red or yellow (Figure). Seven of the nine hotspots abut or overlap with these communities (Figure).

Conclusions:
Geographic analysis of MSU data shows that redlined communities persistently remain active areas of stroke prevalence. Geospatial analysis can be used to leverage MSU deployment for these high risk communities.
Thrombolysis for Ischemic Stroke Beyond the 4.5-Hour Window: A Meta-Analysis of Randomized Clinical Trials
Authors: Günkan Ahmet , Ferreira Marcio Yuri , Vilardo Marina , Scarcia Luca , Bocanegra-Becerra Jhon E. , Cardoso Leonardo Januario Campos , Fabrini Paleare Luis F. , de Oliveira Almeida Gustavo , Semione Gabriel , Ferreira Christian , Ciccio Gabriele , Mujanovic Adnan , Jabbour Pascal , Serulle Yafell , Nguyen Thanh N. , Baron Jean-Claude
Published: January 2025

BACKGROUND:

A minority of patients with stroke qualify for intravenous thrombolysis (IVT) within 4.5-hour window. The safety and efficacy of IVT beyond this period have not been well studied.

METHODS:

We systematically searched MEDLINE, Embase, Cochrane, and
ClinicalTrials.gov
for relevant randomized clinical trials. Randomized clinical trials comparing IVT versus standard medical care in patients with ischemic stroke beyond 4.5 hours of symptom onset or last known well without mechanical thrombectomy (MT) were included. Primary outcomes were excellent (modified Rankin Scale score of 0–1) and good (modified Rankin Scale score of 0–2) functional outcomes at 90 days, symptomatic intracerebral hemorrhage (sICH), and death at 90 days. Pooled odds ratios (ORs) with 95% CIs were calculated using a random-effects model. Heterogeneity was assessed by
Q
test and quantified by
I
² values.

RESULTS:

Eight randomized clinical trials (1742 patients; mean age, 69.8±9 years, 63.5% men) were included. Compared with standard medical care, IVT achieved higher rates of excellent (OR, 1.43 [95% CI, 1.17–1.75];
Q
=2.30;
P
=0.94;
I
2
=0%) and good functional outcomes (OR, 1.36 [95% CI, 1.12–1.66];
Q
=2.07;
P
=0.96;
I
2
=0%) at 90 days but also increased sICH rates (OR, 4.25 [95% CI, 1.67–10.84],
Q
=0.48;
P
=0.99;
I
2
=0%). Mortality at 90 days did not significantly differ between treatment groups (OR, 1.28 [95% CI, 0.87–1.89];
Q
=4.63;
P
=0.59;
I
2
=0%). Subanalyses yielded numerically higher odds of excellent functional outcomes when patients were selected with perfusion imaging (3 studies, OR, 1.45 [95% CI, 1.08–1.94]) compared with diffusion-weighted imaging–fluid-attenuated inversion recovery mismatch (3 studies, OR, 1.34 [95% CI, 0.94–1.91]) and when treated with tenecteplase (3 studies, OR, 1.47 [95% CI, 1.06–2.04]) compared with alteplase (5 studies, OR, 1.38 [95% CI, 1.08–1.78]).

CONCLUSIONS:

IVT for ischemic stroke beyond 4.5 hours, without MT, led to increased odds of excellent and good functional outcomes compared with standard medical care, despite higher odds of sICH, and a nonsignificant numerical increase in mortality.
Peers Affect Personality Development
Authors: Shan Xiaoyue , Zölitz Ulf
Published: January 2025

Do people around us influence our personality? We investigate this question through a field experiment where we randomly assign university students to study groups. We find personality spillovers along three dimensions: students become more conscientious when assigned to conscientious peers, more open-minded when assigned to open-minded peers, and more competitive when assigned to competitive peers. We find no effects for peers' extraversion, agreeableness, or neuroticism. Our findings are consistent with students' adopting peer traits that are predictive of academic achievement. Our paper provides novel evidence on spillovers in noncognitive skills and establishes that socialization with peers affects personality development.
Pauronemoides lorestanensis n. sp. (Tylenchomorpha, Paurodontidae), from the rhizosphere of grasses in Lorestan province, western Iran
Authors: Mirzaie Fouladvand Zeinab , Atighi Mohammad Reza , Pourjam Ebrahim , Kanzaki Natsumi , Giblin-Davis Robin M. , Pedram Majid
Published: January 2025

Pauronemoides lorestanensis n. sp., the fifth species of the newly established genus Pauronemoides, is described and illustrated based on morphological, morphometric and molecular data. The new species was recovered from a soil sample collected from the rhizosphere of grasses in Lorestan province. It is characterised by having a medium-sized body (868-1092 μm, females; 714, 710 μm, males), four incisures in lateral fields, asymmetrical knobs of stylet, vulva at 87.9-90.2%, post-vulval uterine sac (PUS) absent, intestine with extension over rectum, and tail dimorphism of sexes and bursa of males reaching near tail end in lateral view. It was morphologically compared with four currently known species of the genus viz. P. siddiqii, P. iranicus, P. mucronatus and P. macrocellus, and is regarded as the cryptic form of P. iranicus, both of which could be separated using some morphological characters and molecular data. Phylogenetic analyses of the partial small and large subunit ribosomal DNA (SSU, LSU D2-D3 rDNA) sequences of the new species were conducted, and the resulting topologies discussed.
Our Markets, Our Selves
Authors: Damrosch David
Published: January 2025

Reflecting on several recurring themes in the contributions to this special issue, this essay discusses the interplay between an individual’s scholarly formation and the markets in which our work circulates, both within academia and beyond. The examples of Matthew Arnold and Michel Foucault can exemplify what Kenneth Burke described as “perspective by incongruity,” with which we can approach the widely disparate works now circulating within world literature, and challenge our own ingrained biases and assumptions in the process.