bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract WMP84: Transferring Patients with Intracerebral Hemorrhages to Tertiary Stroke Centers
Authors: Nguyen Claude , Mir Osman , Vahidy Farhaan , Lopez George , Gonzales Nicole , Savitz Sean
Published: March 2022

Background:
As a tertiary stroke center, we have increased outreach efforts to hospitals in the greater metropolitan region, having a policy to accept all patients with ICH. Comprehensive Stroke Center guidelines mandate receipt of these patients for higher level of care. We assessed the demographics, clinical severity, resource utilization, and proportion of eligibility for clinical trials among transferred patients compared to those directly arriving to our center. With an "open door" policy, we hypothesized that patients accepted from outside hospitals have more severe deficits and worse outcomes than those arriving directly to our center.

Methods:
From our prospectively-collected stroke registry, we reviewed all spontaneous, primary ICH patients from 3/11-3/12. Primary outcome was the proportion of patients with mRS 4-6.

Results:
Among 362 patients, 210 (58%) were transfers. Transferred patients were older (p<0.01), had higher median GCS (p=0.02), and lower NIHSS (p<0.01) than directly-admitted patients (table). Transfers had smaller median ICH volumes (p=0.04), lower ICH scores (p<0.01), and shorter time spent in ICU (p=0.02). Fewer transfers were enrolled in an investigational treatment trial (p<0.01). After adjusting for age, NIHSS, length of stay, ICH volume, presence of IVH, and history of CAD/MI, there was no difference in mRS 4-6 between the groups.

Conclusions:
Contrary to our expectation, transferred patients had more favorable ICH characteristics with similar outcomes compared to directly admitted patients. Transferred patients required significantly fewer surgical procedures and a significant number of patients had very small hemorrhages and/or did not have IVH, excluding them from clinical trials. Over half arrived >24 hrs or had unknown onset. Our results raise the need to analyze cost-benefits and resource utilization of transferring patients with milder ICH.
Abstract WP104: Chemical Preconditioning Enhances the Effectiveness of Stem Cell Therapy in Ischemic Stroke
Authors: Sakata Hiroyuki , Niizuma Kuniyasu , Narasimhan Purnima , Wakai Takuma , Fujimura Miki , Tominaga Teiji , Chan Pak H
Published: March 2022

Introduction:
Transplantation of neural stem cells (NSCs) provides a promising therapy for stroke. Its efficacy, however, might be limited because of massive grafted-cell death following transplantation, as well as insufficient capability for tissue repair. Chemical preconditioning primes the cells to the ‘‘state of readiness’’ to withstand the rigors of lethal ischemia. In this study, we investigated whether cellular reprogramming of NSCs with minocycline or interleukin-6 (IL-6), both of which are known to possess cytoprotective properties, facilitates the effectiveness of stem cell therapy in ischemic stroke.

Methods:
NSCs harvested from the subventricular zone of fetal mice were preconditioned with minocycline (10 μM) or IL-6 (20 ng/ml) for 24 hours
in vitro
. For an
in vitro
study, the NSCs were subjected to oxygen-glucose deprivation and reoxygenation (n=4). For an
in vivo
study, the NSCs were transplanted into mouse brains 6 hours or 7 days after transient middle cerebral artery occlusion (n=8). Histological and behavioral tests were examined from days 0 to 28 after stroke.

Results:
Minocycline preconditioning up-regulated the expression of Nrf2 (2.7-fold), as well as Nrf2-regulated antioxidant genes (HO-1: 4.0-fold/NQO1: 20-fold), and induced the NSCs to release paracrine factors, including BDNF, NGF, GDNF, and VEGF. IL-6 preconditioning activated STAT3-mediated up-regulation of SOD2 (2.3-fold), a primary mitochondrial antioxidant enzyme, and induced VEGF secretion (2.2-fold). Transplantation of minocycline- or IL-6-preconditioned NSCs significantly reduced grafted cell death, attenuated infarct size, and improved neurological performance compared with non-preconditioned NSCs. This minocycline- or IL-6-induced amelioration of ischemic insults was abolished by transfecting the NSCs with Nrf2- or STAT3-small interfering RNA before transplantation.

Conclusions:
Chemical preconditioning, which reprograms NSCs to tolerate oxidative stress after ischemic reperfusion injury and to induce trophic effects, is a simple and beneficial approach for enhancing the effectiveness of cell transplantation therapy in ischemic stroke.
Abstract WP109: Glucagon-Like Peptide-1 Has Anti-Inflammatory Effects Through Increasing IB1, A Scaffold Regulator Of JNK, In Cerebral Ischemia
Authors: Kim Soojin , Yang Jiwon , Jeong Jaewon , Jeong Siyun , Jeong Hyesun , Kim Bokyung , Kim Jeong-Soo , Song Yun Seon
Published: March 2022

Background and Purpose:
Hyperglycemia is frequently observed in patients with acute ischemic stroke, and conversely, diabetic patients showed a high frequency of stroke. This correlation indicates shared mechanisms in pathology. Glucagon like peptide-1 (GLP-1) stimulates glucose-dependent insulin secretion and is used to treat type 2 diabetes mellitus. Recently, beyond the glucose-lowering effect, GLP-1 has been reported to possess neuroprotective effects. We therefore investigated the neuroprotective mechanism of GLP-1 receptor (GLP-1R) agonist exendin-4 (ex-4) after cerebral ischemia-reperfusion injury.

Methods:
Male Sprague-Dawley rats were subjected to 60 min of middle cerebral artery occlusion (MCAO) with intracerebroventricular (i.c.v) pretreatment of ex-4. Oxygen glucose deprivation was induced to primary neuron cultures in an anaerobic chamber. Changes of genes were further confirmed by QPCR and Western blot, and siRNA was used to ascertain the mechanism.

Results:
Ischemia-reperfusion injury reduced the expressions of GLP-1R by 46.3% (p<0.01)
;
higher oxidative stress in SOD2 KO mice induced lower expression of GLP-1R, but higher in SOD1 Tg mice. Down regulated GLP-1R by ischemic injury was 70% restored by GLP-1R agonist, ex-4 (p<0.01), which resulted in significant reduction of infarct volume. Intracellular cyclic AMP levels, a second messenger of GLP-1R, were also increased by 2.7 fold according to a high GLP-1R expression (p<0.01). Moreover, our results showed that ex-4 attenuated pro-inflammatory Cyclooxygenase-2 (Cox-2) by 85% (p<0.001) and prostaglandin E2 by 27% (p<0.01) after MCAO. The c-Jun NH
2
terminal kinase (JNK) signaling that stimulates activation of Cox-2 was 36% inhibited by the i.c.v injection of ex-4 at 24 h (p<0.05). Islet-brain 1 (IB1), a scaffold regulator of JNK, was 1.7 fold increased by ex-4 at 24 h. Suppression of IB1 levels with the use of siRNA impaired the anti-inflammatory effects of ex-4 against ischemic injury.

Conclusions:
GLP-1R activation by ex-4 resulted in reduction of Cox-2 through increasing IB1, which led to anti-inflammatory neuroprotection in stroke. Our study suggests that anti-inflammatory action of GLP-1 could be a new strategy for the treatment of stroke accompanied by hyperglycemia.
Abstract WP11: Decreased Intraprocedural End Tidal Carbon Dioxide Is Associated With Unfavorable Functional Outcome After Endovascular Intervention For Acute Ischemic Stroke
Authors: Takahashi Courtney E , Macri Elizabeth , Hinson Holly , Raines Joshua , Multani-Kohol Anmol , Lutsep Helmi , Clark Wayne , Brambrink Ansgar , Aziz Michael , Fields Jeremy
Published: March 2022

Introduction:
Patientsundergoing endovascular intervention for acute stroke may have better outcomeswhen managed with conscious sedation (CS) instead of general anesthesia (GA). Previous investigations have not elucidated aclear mechanism for this observation.

Hypothesis:
Wehypothesize that decreased intraprocedural blood pressure and decreased end tidal CO2 would be associated with worsened functional outcomes at 90 days.

Methods:
Consecutive patients undergoing stroke interventions between August 2007 and December 2010 were identified from a prospective database. Clinical data was then extracted by retrospective chart review. Outcomes were stratified according to 90 day modified Rankin Scale (mRS), with scores of 0-3 designated as favorable and 4-6 as unfavorable. Variables significantly associated with outcome in univariate analysis were also examined in multivariate analysis, controlling for well-established predictors of functional outcome: age, medical comorbidities, TICI score, and NIH stroke scale score.

Results:
Of the 106 patients identified, 86 had complete medical and anesthetic records and could be included in the study. None of the measured parameters, including the absolute BP, the absolute decrease in BP, and the relative decrease in BP were associated with functional outcome at 90 days. On the other hand, end tidal carbon dioxide (ETCO2) at 60 min and 90 min was significantly associated with outcome in both univariate and multivariate analysis, controlling for other well-established predictors of functional outcome.

Conclusion:
Intraprocedural hypocapnia was associated with unfavorable functional outcomes at 3 months, whereas intraprocedural blood pressure was not related to functional outcome. This finding suggests that intraprocedural hypocapnia, rather than the hemodynamic effects of anesthesia, may account for the differences in outcome between GA and CS patients.
Abstract WP111: The Impact Of Statins On The Blood Brain Barrier Might Adversely Affect Autologous Bone Marrow Cell Therapy In Acute Stroke
Authors: Mir Osman , Yang Bing , Nguyen Claude , Parsha Kaushik , Savitz sean I
Published: March 2022

Background:
Autologous bone marrow derived mononuclear cells (MNCs) enhance stroke recovery in animals and are being tested in stroke clinical trials. Some patients at the time of stroke are on statins, which reduce blood-brain barrier permeability. Since MNCs may need to enter the brain to enhance brain repair, statins might reduce the efficacy of MNCs. We studied the impact of statin exposure on MNC delivery into the brain.

Methods:
In this double blind placebo controlled experiment, 30 Long Evans rats were randomized into 4 groups (fig). Stroke was induced by MCA suture occlusion for 90 min. Atorvastatin (or vehicle) was given PO daily for 5 days before stroke. Animals that received MNCs underwent a bone marrow harvest at 22 hrs after stroke followed by isolation, labeling with Q-tracker, and MNC re-infusion by intra-carotid artery delivery. BBB permeability was assessed by Evans Blue.

Results:
Pre-treatment with atorvastatin and post-treatment with MNCs led to a significant reduction in BBB breakdown. (p = 0.003). Neither atorvastatin nor MNCs alone had a significant effect on the BBB. Pre-treatment with atorvastatin significantly reduced the number of MNCs in the brain (p = .02)

Conclusions:
Exposure to atorvastatin before stroke reduces the number of MNCs entering the brain when the cells are administered at 24 hrs after stroke. Atorvastatin in combination with MNCs led to substantial reduction in BBB permeability, suggesting that atorvastatin and MNCs may have a synergistic effect on the BBB which could consequently prevent CNS entry of MNCs. These results have important translational implications for the design of clinical trials testing bone marrow cell therapies in patients with acute stroke. Statins might potentially reduce the number of cells entering the brain which could reduce the potential benefits of cell therapies that need to enter the brain to enhance recovery. We are studying if atorvastatin impairs recovery in rats treated with MNCs.
Abstract WP112: The TLR9 Ligand, CpG-ODN, Induces Protection Against Cerebral Ischemia/reperfusion Injury Via A PI3K/Akt Dependent Mechanism
Authors: Lu Chen , Ha Tuanzhu , Wang Xiaohui , Liu Li , Schweitzer John , Kalblfeisch John , Williams David , Li Chuanfu
Published: March 2022

Background:
Toll-like receptors (TLRs) are involved in the pathophysiology of cerebral ischemia/reperfusion injury. TLR9 is an intracellular TLR which is located in the endosome and recognizes CpG-DNA. The role of TLR9 in ischemic stroke has not been investigated. We hypothesized that TLR9 activation would induce protection against cerebral I/R injury.

Methods:
To evaluate our hypothesis, we treated C57BL/6 mice with CpG-ODN (10 μg/mouse, n=8), by i.p. injection one hr before the mice were subjected to cerebral ischemia (60 min) followed by reperfusion (24 hrs). Scrambled-ODN served as control-ODN (10 μg/mouse, n=8). Untreated mice, subjected to cerebral I/R, served as I/R control (n=8). We also examined the effect of inhibitory CpG-ODN (iCpG-ODN), a TLR9 antagonist, on cerebral I/R injury (n=8). In addition, the therapeutic effect of CpG-ODN on cerebral I/R injury was investigated by i.v. injection of CpG-OND 15 min after cerebral ischemia.

Results:
CpG-ODN administration significantly attenuated cerebral I/R induced infarct volume (↓ 75.8%, p<0.05) improved neurological scores and increased survival rate when compared with the untreated I/R group. Of greater significance, therapeutic administration of CpG-ODN also significantly reduced infarct volume by 52.6% (p<0.05) compared with untreated I/R mice. Neither control-ODN, nor iCpG-ODN altered I/R-induced cerebral injury or neurological deficits. Nissl staining showed preservation of neuronal morphology in the ischemic hippocampus in CpG-ODN treated mice. Immunoblot showed that CpG-ODN administration increased Bcl-2 levels and attenuated Bax, Fas-L, TNF-α, and caspase-3 activity in ischemic brain tissues. CpG-ODN treatment also significantly increased the levels of p-Akt and p-GSK-3β. PI3K inhibition with LY29004 abolished CpG-ODN-induced protection against cerebral I/R injury.

Conclusion:
The data suggest that the TLR9 ligand, CpG-ODN, significantly reduces focal cerebral I/R injury via a PI3K/Akt-dependent mechanism. The data also indicates that therapeutic administration of CpG-ODN during cerebral ischemia is effective in reducing cerebral I/R injury.
Abstract WP117: Ischemic Post-conditioning Partially Reverses Cell Cycle Re-entry Following Transient Ischemia/Reperfusion Injury
Authors: Zhao Haiping , Luo Yumin , Wang Rongliang , Liu Xiangrong , Yan Feng , Liu Xiaomeng , Li Sijie , Leak Rehana K. , Ji Xunming
Published: March 2022

Background and purpose
—The neuroprotective effects of ischemic postconditioning (IPostC) are well established but the underlying mechanism is still unknown. We began to explore this critical gap in the field by genomic comparison of ischemic rat cortex following transient middle cerebral artery occlusion (tMCAO) alone or tMCAO+IPostC.

Methods and Results
—Microarray analysis revealed that tMCAO-induced transcriptional changes in 40 cell cycle regulators were ameliorated by IPostC, suggesting that IPostC reversed neuronal cell cycle re-entry. RT-PCR, immunoblotting, and immunofluorescence were subsequently used to quantify or localize the cell proliferation marker proliferating cell nuclear antigen (PCNA), positive and negative cell cycle regulators, and related signaling molecules. As expected, IPostC reversed the rise in mRNA levels of positive cell cycle regulators cdcb1, cdk1, cdca2, cadca3, and cdca7. Elevations in cyclin D1 and neuronal cyclin A2 were similarly inhibited. tMCAO-induced phosphorylation of extracellular signal-regulated kinase (p-ERK), glycogen synthase kinase-3β (p-GS3K3β), and cAMP response element binding protein (p-CREB) were also all depressed by IPostC. Furthermore, p-ERK colocalized with neuronal cyclin A2.

Conclusions
—The present study demonstrates the potent inhibitory effect of IPostC treatment on tMCAO-induced cell-cycle reentry and on ERK/CREB and GSK3β/CREB signaling. Because neuronal cell cycle re-entry is pro-apoptotic, these findings lend insight into potential mechanisms underlying neuroprotection with IPostC.
Abstract WP121: Brain Structures Anormalites Detected By Voxel Based Morphometry In Individuals With Asymptomatic Carotid Stenosis.
Authors: Avelar Wagner M , D’Abreu Anelyssa , Lima Fabricio O , Yasuda Clarissa L , Coan Ana Carolina , Campos-Herrera Cynthia R , Guillaumon Ana T , Min Li L , Cendes Fernando
Published: March 2022

Background:
Studies of patients with asymptomatic carotid stenosis have shown significant cognitive decline in this individuals compared to groups without stenosis. Our study aims to investigate the occurrence of subtle gray and white matter decrease in patients with asymptomatic carotid stenosis through Voxel Based Morphometry (VBM) analysis.

Methods:
Twenty-seven patients (7 women, mean age of 71 years, range 51- 78 years) with unilateral asymptomatic carotid stenosis (>70%) or occlusion, defined by angiotomography (CTA), were submitted to MRI and images were analyzed with VBM. MR images were acquired on a 3T-MR scanner, with sequence 3D sagittal T1-weighted (voxel size 1x1x1 mm,TR = 22 ms, TE = 9 ms, flip angle = 35°, matrix = 256x220). Images of patients with left carotid stenosis were flipped in the right-left orientation thus all hemispheres ipsilateral to the stenosis were aligned. For statistical comparisons, we used images of 27 healthy control subjects matched for sex and age with patient group (7 women, mean age of 68 years, range 54-82). VBM analysis was performed with VBM8/SPM8 toolbox (two-sample T-Test, P<0.001 uncorrected).

Results:
VBM analysis demonstrated significant and diffuse gray matter reduction in both hemispheres of patient group. However, these abnormalities were more pronounced in the area correspondent to the anterior circulation of the hemisphere ipsilateral to the carotid stenosis. In contrast, white matter abnormalities detected by VBM were less evident and with symmetrical distribution in both hemispheres.

Conclusion:
Our findings suggest that asymptomatic carotid stenosis/occlusion is associated with subtle gray matter reduction predominantly in the ipsilateral hemisphere. This is in accordance with previous data demonstrating cognitive decline in these patients and it may imply that there is significant hemodynamic disturbance secondary to these stenosis.
Abstract WP131: Correlation of Cardiac Derangement in Patients with Right-Sided Ischemic Stroke and the Severity of Insular Damage
Authors: Min Jiangyong , Pratt Yong H , Alshalian Mhd Khaled , Smith Ryan , Safdar Adnan , Hussain Syed , Kassab Mounzer
Published: March 2022

Objective:
Although it is known that neurogenic cardiac damage can occur after an ischemic stroke, the mapping of the neuroanatomic correlation of ischemic stroke-related myocardial injury remains to be defined. Our previous animal study found a higher incidence of myocardial damage from left-sided insular infarction comparing to the right side. However, the results from various clinical studies have been inconclusive. This clinical study aims to identify a quantitative correlation between adverse cardiac outcomes and insular infarction, left-sided versus right-sided, as well as potential prognostic factors that may be used to aid in assessing patient outcomes and making treatment decisions.

Methods and Results:
A serial measurements of cardiac troponin T (cTnT) and creatine phosphokinase-MB (CK-MB), 12-lead EKG, and two- dimensional echocardiography were performed in 42 patients with MRI-confirmed ischemic stroke involving the insular cortex. The severity of insular damage was measured with diffusion-weighted imaging studies (DWI). Patients with renal failure, recent cardiac ischemic events, or congestive heart failure were excluded. Twenty-two patients (52.4%) had left-sided middle cerebral artery (MCA) infarcts with insular involvement, whereas 20 (47.6%) had a right-sided MCA infarcts involving the insular cortex. When compared to patients with left MCA infarcts involving the insular cortex, patients with right MCA infarcts with insular involvement had significantly higher levels of cTnT elevation. By using the linear regression analysis we also identified a statistically significant correlation between cTnT elevation and severity of right insular damage, instead of the NIH stroke score (NIHSS) as commonly assumed. Moreover, two patients were found to have transient left ventricular wall hypokinesis which mimics Takotsubo cardiomyopathy.

Conclusions:
This study showed that patients with right MCA ischemic stroke involving the insular cortex, comparing to those with left-sided insular stroke, tend to have more severe cardiac insult leading to higher levels of cTnT. The study also identified severity of insular damage as a potential prognostic factor in assessing cardiac derangement as a complication of insular infarction.
Abstract WP134: Expression of Nox4 and Nox5 are Associated with Carotid Vulnerable Atherosclerotic Plaque in a Swine Model
Authors: Shi Zhong-Song , Wang Jin-Shan , Jiang Xiao-Bing , Yuan Wei-Si , Liu Zhong
Published: March 2022

Purpose:
Fibrous cap rupture from atherosclerotic plaque can send distal emboli and lead to stroke in patients with carotid disease. The NADPH oxidases (Nox) family play an important role in the pathophysiology of atherosclerosis. However, the relationship of Nox expression with atherosclerotic plaque vulnerability remain elusive. We aim to assess the association of Nox4 and Nox5 expression with carotid plaque vulnerability in a swine model.

Methods:
Carotid atherosclerosis was induced in miniswines using partial ligation and high cholesterol diet, and a minimum 70% stenosis was confirmed by Doppler ultrasonography. Carotid artery sections were obtained for histologic examination and immunohistochemical study for Nox4 and Nox5 at 3 months. The atherosclerotic lesions of AHA type IV to VI were defined as advanced plaques. The association of Nox4 and Nox5 expression in the plaque with the feature of plaque vulnerability was analyzed.

Results:
Seventy-five carotid segments from ten carotid artery models had fibrous cap plaques with AHA type IV to VI. Distal embolism with the presence of atheroemboli was found in all rete mirabilis, and deemed to be from the ipsilateral carotid plaques. Positive staining of Nox4 and Nox5 were mostly distributed in the surrounding of lipid core, endothelium and plaque shoulder. Increased expression of Nox4 in the plaque was associated with the features of a large lipid core, marked foam cell and thin fibrous cap (p<0.01). Overexpression of Nox5 in the plaque was associated with marked foam cell and cap rupture (p<0.05). Co-overexpression of Nox4 and Nox 5 in the plaque was associated with thin cap (p<0.05). Low expression of both Nox4 and Nox5 in the plaque was associated with less thin cap and less cap rupture (p<0.01). There was a higher frequency of thin cap and cap rupture in 27 plaques with co-overexpression of Nox4 and Nox 5 than in 26 plaques with low expression of both Nox4 and Nox5.

Conclusion:
Nox4 and Nox5 are both expressed in carotid atherosclerotic plaques in a swine model, and their overexpression in carotid plaques are associated with thin fibrous cap and cap rupture. Upregulated Nox4 and Nox5 may participate in the process of vulnerable atherosclerotic plaque and may be used as a target for reducing the risk of distal embolism.
Abstract WP141: The Role Of Paroxysmal Atrial Fibrillation In Patients With Retinal Artery Occlusion (rao)
Authors: Ammermann Antje , Best Janina , Arnold Inka , Duvinage Andre , Stahrenberg Raoul , Edelmann Frank , Groeschel Klaus , Feltgen Nicolas , Wachter Rolf
Published: March 2022

Background:
Patients with retinal artery occlusion (RAO) have a 2.0 fold increase in risk for subsequent stroke and share similar risk factors with stroke patients. The pathophysiologic role of atrial fibrillation (AF), especially in its paroxysmal presentation, is poorly understood. We hypothesized that AF is similarly prevalent in RAO as in ischemic stroke (IS).

Materials and methods:
In the Find-AF-eye trial, 50 patients with RAO were subsequently recruited into a prospective cohort study. 49 patients with venous retinal thrombosis (VRT) and 280 patients with ischemic stroke (IS) served as controls. Comprehensive evaluation included carotid artery Duplex examination, 7-day Holter ECG, transthoracal and transesophageal echocardiography and assessment of lipid and glucose status. AF was defined as an atrial arrhythmia for at least 30 seconds.

Results:
6 RAO patients (12.0 %), 5 VRT patients (10.2 %) and 48 IS (17.1 %) patients had a history of AF or had AF in the admission ECG. During 7-day Holter, 34 additional patients were diagnosed to have paroxysmal AF during 7-day Holter (2 RAO, 4 VRT, 28 IS patients). The overall prevalence of any AF was not significantly different between RAO (16.0 %) and VRT (18.3 %), p=0.79, but tended to be higher in IS (27.1 %), p=0.109 vs. RAO and p=0.195 vs. VRT.

Conclusion:
Our data do not support a relevant pathophysiologic role of AF in patients with RAO.
Abstract WP148: The BRIDGE Project (
BRIDG
ing the gap in strok
E
management):Trans-Atlantic Differences in Management of Carotid Stenosis
Authors: Balucani Clotilde , Arnedo Vanessa , Leys Didier , Mas Jean-Louis , Brown Martin , Grotta James C , Gonzales Nicole R , Savitz Sean I , Hacke Werner , Brott Thomas , Levine Steven R
Published: March 2022

Background:
Optimum management of carotid stenosis, both symptomatic (sx) and asymptomatic (asx), remains controversial despite clinical trials evaluating Carotid Endarterectomy (CEA) and Carotid Stenting (CAS).

Objective:
We compared attitudes in management of carotid stenosis between experts in Europe (EU), and North America (NA).

Methods:
From April 2011 to July 2012, a 3-round, email-Delphi survey was sent to members of the European Stroke Organisation (n=390) and to a list of NA stroke neurologists developed at the University of Texas at Houston Stroke Program (n=289). Those completing the survey were shown all responses broken down by EU/NA after each of the first 2 survey rounds. Continent specific consensus was defined a priori to be > 80% agreement.

Results:
100 (15%, of which 73% EU) participated in all 3-Delphi rounds, 19% of all EU vs 9% NA (χ2=11.62, p=0.0007): 76% male; 69% treating between 1-8 new cases of carotid stenosis per month. In the final round, EU reached consensus in 7/11 statements (3 reached in phase-I), while NA did in 4/11 (1 reached in phase-I).Ninety-percent of EU vs 70% of NA (χ2=8.09, p=0.017) disagreed that CAS and CEA are equivalent treatments for sx carotid stenosis, and stated that CEA is superior. There remains a significant difference between EU and NA when considering ipsilateral stroke and death < 30 days as primary outcome (χ2=12.18, p=0.007). Sixty-nine-percent of NA agreed that there is a stronger indication for CAS over CEA in patients < 65 years for sx carotid stenosis whereas 55% of EU (χ2=11.39, p=0.023) disagreed with the statement. When asked how likely they would recommend CEA for an asx carotid stenosis, 81% of EU and 80% of NA said ‘sometimes’. When asked how likely they would recommend CAS for an asx carotid stenosis, 62% of NA said ‘sometimes’ vs 60% of EU said ‘never’(χ2=3.54, p=0.06).

Conclusion:
There are several clear differences in attitudes regarding the management of carotid stenosis between EU and NA: EU has a stronger attitude towards superiority of CEA while in NA there is more equipoise between the two treatments. Areas of lack of consensus may provide direction for future clinical trials.
Abstract WP149: Anti-inflammatory Effect Of Cilostazol On Silent Brain Infarction
Authors: Lee Jinho , Lee Kyu-Yong , Kim Young-Seo , Kim Hyun Young , Kwon Hyuk Sung , Park Hyun-Hee , Choi Na-Young , Lee Eunhye , Son Jeongu , Yu Hyun-Jeung , Lee Yeong Bae , Koh Seong-Ho
Published: March 2022

Introduction:
Silent brain infarcts (SBI) are seen on brain computed topography or magnetic resonance imaging without any clinical symptoms suggestive of transient ischemic attack or stroke. SBI are associated with the risk of subsequent stroke and dementia. Various inflammatory markers have been reported to correlate with SBI. After the Cilostazol Stroke Prevention Study, many studies have focused on anti-inflammatory effect of cilostazol.

Hypothesis:
We investigated the anti-inflammatory effect of cilostazol in the patients with silent brain infarcts by measuring temporal profile of inflammatory markers.

Methods:
We prospectively and consecutively enrolled 26 patients with silent brain infarcts, who agreed signed informed consent, and then treated with cilostazol (200mg/day) for 3 months. Several inflammatory markers including macrophage migration inhibitory factor (MIF), stromal cell-derived factor-1 (SDF-1),vascular endothelial growth factor (VEGF), visfatin, and matrix metalloproteinase 9 (MMP-9) were repeatedly measured at baseline, 1 week, and 3 months.

Results:
Levels of MIF, visfatin, and MMP-9 were significantly decreased 3months after cilostazol treatmentwhen compared with baseline and 1week (p < 0.05). There is no significant difference in SDF-1 and VEGF.

Conclusion:
After cilostazol treatment for 3 months, MIF, visfatin, and MMP-9 among various inflammatory markers notably decreased. MIF has been reported as a pro-inflammatory marker by promoting cell death and facilitating the atherogenesis process. Visfatin stimulates the release of cytokines and is induced by inflammatory stimuli in cells involved in innate immunity, such as neutrophils, monocytes, macrophages, and epithelial cells. MMP-9 has been shown to contribute to blood-brain barrier disruption, infarct formation and hemorrhagic transformation. Therefore, these factors play important roles in pathogenesis or consequence after ischemic stroke. Based on our findings, we cautiously suggest that cilostazol has anti-inflammatory effect affecting inflammatory markers such as MIF, visfatin and MMP-9 and further investigation about relationship between these markers and clinical significance is needed.
Abstract WP159: Acute Administration of Ethanol Reduced Brain Apoptosis by Regulating Expression of Apoptotic Proteins in Ischemic Stroke
Authors: Fu Paul , Peng Changya , Geng Xiaokun , Asmaro Karam , Guthikonda Murali , Ding Yuchuan
Published: March 2022

Objectives:
In our recent studies, acute ethanol administration appears to play a neuroprotective role after the onset of ischemic stroke by reducing infarct volume and behavioral dysfunction (
Stroke. 2012 43(1):205-10
). In the present study, we sought to identify whether the ethanol-derived neuroprotection is associated with a reduction in apoptosis.

Methods:
Ethanol was given by intraperitoneal injections to Sprague-Dawley rats after 2 hours of middle cerebral artery (MCA) occlusion, followed by reperfusion. The actual degree of apoptotic cell death in control, ischemic rats, and ischemic rats treated with 1.5 g/kg ethanol was determined by the Cell Death Detection ELISA Assay (Roche). Levels of pro-apoptotic (Caspase-3, Bcl-2-associated X “BAX”, and Apoptosis-Inducing Factor “AIF”) and anti-apoptotic proteins (Bcl-2 and Bcl-xL) were determined by Western blot at 3 and 24 hours after reperfusion.

Results:
Rats treated with ethanol at the 1.5 g/kg dosage demonstrated significantly reduced cell death as compared to those of stroke without treatment. Acute ethanol administration at the 1.5 g/kg dose significantly promoted the expression of anti-apoptotic factors and decreased the expression of pro-apoptotic proteins at 3 hours after reperfusion. This effect was maintained at 24 hours for Caspase-3 and AIF, but not for Bcl-2, Bcl-xL, and Bax. We further demonstrated that administration of low dose of ethanol at 0.5 g/kg was not as effective in regulating protein expression as the 1.5 g/kg dose (1.5 g/kg dose being equivalent to the legal driving limit).

Conclusions:
Our study suggests that administration of ethanol at a 1.5 g/kg dosage after onset of stroke reduces apoptosis by creating a differential protein profile, with increased expression of anti-apoptotic proteins and decreased expression of pro-apoptotic ones. This study helps in validating ethanol as a new therapeutic approach in neuroprotection after stroke, and proposes a possible mechanism for its anti-apoptotic effect on neuronal cells.
Abstract WP160: A Post-Hoc Assessment of Current Hormone Therapy on Revascularization Risk in Women: The Carotid Revascularization Endarterectomy versus Stenting Trial (CREST)
Authors: Mackey Ariane , Lutsep Helmi L , Milot Genevieve , Voeks Jenifer H , Howard Virginia J , Hughes Susan E , Tom MeeLee , Longbottom Mary E , Sheffet Alice J , Brott Thomas G
Published: March 2022

Background:
Hormone replacement therapy (HRT) was among factors considered in a post-hoc assessment of the risk of revascularization by carotid artery stenting (CAS) or carotid endarterectomy (CEA) in women enrolled in CREST.

Methods:
Of the 872 women in CREST, 775 (89%) were post-menopausal and current HRT status was known in 739 (95%). The study composite outcome was defined as any stroke, myocardial infarction, or death during the periprocedural period, plus ipsilateral stroke over a 4-year follow-up period. Treatment groups were combined and differences in the composite outcome were assessed by current HRT at baseline.

Results:
There were 77/739 (10%) current HRT users. HRT users were more likely to be symptomatic at baseline than non-users (65% vs. 52%; p = 0.027), and were less likely to be diabetic (19% vs. 32%; p = 0.024). However, they were similar in most other factors including age, race, hypertension, dyslipidemia, smoking status, and length of follow-up (p > 0.10). There were no (0) periprocedural events among the 77 HRT users while there were 43 (6.5%) events among the 662 non-users (p = 0.017). Among those event-free at the end of the periprocedural period, there was little evidence of an impact of baseline HRT on the risk of ipsilateral stroke with 2 (2.6%) post-procedural events among 77 HRT users and 12 (1.9%) among 619 non-users.

Conclusion:
We found that women on current HRT have lower periprocedural risk associated with CAS or CEA than non-users, but little difference in risk after the procedural period. The mechanism for this unexpected finding is elusive. We urge caution in the interpretation of this post-hoc observation and encourage replication or refutation by other revascularization studies with similar data.
Abstract WP163: 3D-versus 2D-Ultrasound for Plaque Analysis of Internal Carotid Arteries with Gray-Scale Median
Authors: Macharzina Roland R , Grabs Anna , Fan Nian , Stajzel Roman , Vach Werner , Neumann Franz-Josef , Zeller Thomas
Published: March 2022

Background:
Gray-Scale Median (GSM) analysis of carotid artery stenosis allows quantification of plaque echogenicity, correlates with histology and showed an association with symptoms and cerebral embolic findings. The aim of the study is to demonstrate whether several systematically aquired sections of 3-dimensional Power-Doppler ultrasound (3D-PDUS) datasets comprising whole plaque stenoses provide different GSM than single sections acquired by 2D-PDUS as commonly used for this purpose.

Methods:
After informed consent, 27 patients were scanned with a 3D-ultrasound (US) probe at 10 Mhz. GSM-analysis was performed offline with a specially designed software (Matlab) in 2D longitudinal scans adjusted to the vessel center line, as well as 3 parasagital - longitudinal sections parallel to each other and 3 views rotated around the center of the plaque, that were aquired off-line from the 3D-datasets by multiplanar rendering. For comparison of the GSM, the median differences between 3D- and the 2D-images as well as standard deviations (SD) were calculated. Mixed model regression analysis was used for further descriptive statistics.

Results:
The GSM differences between the 3D-parallel and the central longitudinal 2D-reference section showed a markedly higher proportion of the variance due to image-to-image (63%) versus inherent technical-methodological scattering (37%), that was not found for rotated 3D sections (54 versus 46%). The GSM of the longitudinal 3D-sections correlates significantly with the GSM of the 2D-reference section (r = 0.60) as do the rotated 3D views (r = 0.52). Correlation coefficients of the central 3D- with the 2D-longitudinal section differed significantly, when rotation was performed (r = 0.63) instead of sagital rendering (r = 0.85, p < 0.05). Significant over- versus underestimations were noted for high versus low GSM values in the 3D parasagital and rotated views compared to the 2D sections.

Conlusions:
Variations of the GSM values in between the 3D-sections were largely due to real differences of the echogenicity. The GSM of a single 2D-section may not be representative for the whole 3D plaque structure. Parasagital section rendering should be prefered to analyse whole plaque GSM over rotating sections.
Abstract WP166: Factors Associated with Proximal Carotid Axis Occlusion in Patients with Acute Stroke and Atrial Fibrillation
Authors: Sakamoto Yuki , Sato Shoichiro , Kuronuma Yuka , Nagatsuka Kazuyuki , Minematsu Kazuo , Toyoda Kazunori
Published: March 2022

Background and purpose
Patients with atrial fibrillation (AF) are more likely to exhibit proximal carotid axis occlusion than those without AF. However, clinical characteristics associated with proximal vessel occlusion (PVO) in acute stroke patients with AF are not fully known. This study was aimed to elucidate the factors correlated with PVO.

Methods
Consecutive patients with acute ischemic stroke in the anterior circulation and AF who underwent MRA within 24 h from onset were retrospectively enrolled. Prior users of warfarin were excluded. Patients were divided into 3 groups based on the site of arterial occlusion: occlusion at the internal carotid artery (ICA); at the horizontal segment of the middle cerebral artery (MCA, M1); and at the MCA branch or no identifiable occlusion. Clinical characteristics were compared between the 3 groups, and the factors associated with proximal vessel occlusion were evaluated with ordinal logistic regression analysis. All variables identified on univariable analyses with p values <0.1 were entered into the model.

Results
A total of 258 patients (127 women, median 80 years old [interquartile range 71-86], median NIHSS score was 15 [6-21]) were studied. MRA was performed median 2.9 h [1.6-10.3] after stroke onset. Occlusion site was the ICA in 34 patients, M1 in 78, and MCA branch or no occlusion in the remaining 146. As the occlusion site was more proximal, patients were older and more female, the initial NIHSS score was higher, levels of D-dimer and brain natriuretic peptide (BNP) were higher, and histories of heart failure and systemic embolism were more common. On multivariable ordinal logistic regression analysis, female sex (OR 2.02, 95%CI 1.15-3.56), advanced age (OR 1.37, 95%CI 1.02-1.85 for every 10 years), history of systemic embolism (OR 15.3, 95%CI 1.45-161), and higher BNP level (OR 1.04, 95%CI 1.01-1.09 for every 50 pg/ml) were independent factors associated with increasing the risk of shifting to a more proximal vessel occlusion category.

Conclusion
Female sex, advanced age, history of systemic embolism, and higher BNP level were independently associated with more proximal carotid axis occlusion. Patients with AF having these factors may be prone to have larger thrombus in the heart than those without.
Abstract WP168: Regulatory T Cell Transplantation Inhibits Cerebral Endothelial Inflammation In Mice Transient Focal Ischemia.
Authors: Li Peiying , Hu Xiaoming , Gan Yu , Zhang Feng , Gao Yanqin , Liang Weimin , Chen Jun
Published: March 2022

INTRODUCTION:
Cerebral endothelial cells express large amounts of adhesion molecules, attracting peripheral immune cells to infiltrate into brain parenchyma. Regulatory T cell (Treg) was recently reported as a key cerebroprotective immunomodulator in ischemic stroke.

HYPOTHESIS:
We assessed the hypothesis that Treg transplantation could protect the ischemic brain from endothelial inflammation via cell-cell interaction.

METHODS:
Transient focal cerebral ischemia was induced in C57/BL6 mice by unilateral middle cerebral artery occlusion (MCAO) for 60 minutes. Tregs (2x10
6
/mouse) or same numbers of splenocytes were injected intravenously at 2 hours after MCAO.

RESULTS:
We found that Treg transplantation could inhibit ICAM-1 expression on endothelial cells in vitro by 3.86±0.04 folds (P<0.01) and also at 24 hours after ischemia in vivo, resulting in ameliorated blood brain barrier damage and reduced infiltration of peripheral immune cells, such as T cells, macrophage, and neutrophils. Further study showed that depletion of CCR5 on Tregs reduced the protective effect of Treg transplantation. Real-time PCR demonstrated 134±46 folds (P<0.05) increase of CCL3, the ligand of CCR5 in the ischemic brain at 24 hours after stroke. Immunofluorescence showed that CCL3, possibly released from activated microglia, was closely associated with inflamed endothelial cells. In vitro migration test further revealed that widetype Tregs migrated across the endothelial cell layer towards CCL3; CCR5
-/-
Tregs, however, failed to migrate.

CONCLUSIONS:
In conclusion, Treg transplantation protected the ischemic brain against ICAM-1 experssion on endothelial cells and profoundly inhibited peripheral immune cell infiltration. A novel contributing mechanism was defined that CCR5 and CCL3 mediated recruitment of Tregs to inflamed endothelial cells and played an important role in the cell-cell interaction between Tregs and endothelial cells.
Abstract WP174: Public Perceived Risk of Stroke, Myocardial Infarction, and Cancer
Authors: Anderson Aaron M , Khoury Jane , Frankel Michael , Kissela Brett M , Rademacher Eric , Flaherty Matthew L , Woo Daniel , Khatri Pooja , Lapinski Maria , Alwell Kathleen , Ferioli Simona , Martini Sharyl , Mackey Jason , De los rios la rosa Felipe , Kleindorfer Dawn
Published: March 2022

Introduction:
Stroke is the fourth leading cause of death in the United States, yet community stroke awareness remains low. Perceptions of individual risk prompt changes in health behavior. Previous reports show community awareness is higher for heart disease than stroke. We hypothesized that public perception of their personal risk of MI and cancer would be significantly higher than stroke.

Methods:
Telephone survey respondents were drawn from our biracial population of 1.3 million using random-digit dialing in 2010 to reflect the age, race, and gender distribution of stroke patients, based an ongoing stroke incidence study in the same region.Respondents were asked to rate their risk of having a stroke, heart attack, cancer, and for women, breast cancer on a scale of 0-10. Analysis was restricted to 1959 of 2036 respondents who were of black or white race. Comparisons were made using analysis of covariance to adjust for age, education, hypertension, diabetes, smoking, coronary artery disease (CAD) and prior stroke.

Results:
Respondents were well-matched to previous descriptions of ischemic stroke populations: 28% black, 61% female, with a mean age of 66.3((±14.7). Overall, respondents thought they had the highest risk of MI, followed by stroke and cancer. However, blacks had a significantly lower perceived risk of stroke, MI, and cancer, after adjusting for confounders.

Discussion:
Perceived risk of stroke was higher than we expected compared to other common diseases, second only to heart attack. Blacks had significantly lower perceived risks than whites for stroke, MI, and cancer. Future public awareness campaigns should consider linking risks of stroke with risks of MI, especially as MI and stroke share many preventative strategies. Racial differences in perceived risk should be evaluated as a target for intervention as perceived risk is associated with changes in health behavior.
Abstract WP175: Health Literacy, Knowledge and Competency: Lessons from the SWIFT Community Study
Authors: Quarles Leigh W , Roberts Eric T , Zitouni Molly , Boden-Albala Bernadette
Published: March 2022

INTRODUCTION:
Racial disparities in stroke preparedness and prevention persist. Emerging research emphasizes the importance of stroke knowledge; however significant gaps remain. The aim of this work was to explore factors related to stroke knowledge/preparedness attainment in a stroke-free community setting.

Methods:
The Stroke Warning Information and Faster Treatment Community (SWIFT) study was a randomized stroke preparedness educational intervention, which prospectively enrolled stroke-free community members from 30 Northern Manhattan community-based organizations. This culturally tailored health literate intervention utilized visuals, and interactive sessions to overcome educational and language barriers. Baseline demographics and a validated stroke knowledge score (SKS) were assessed by interviewer administered questionnaires at each of the community sites. Health literacy was assessed using the Short Test of Functional Health Literacy in Adults. At the end of the intervention, we assessed competency of stroke knowledge and preparedness using an open-ended teach back methodology.

Results:
The cohort included 423 stroke free community residents; mean age 64.1 years; 77% female; 30% white, 27% black, 40% Hispanic. Mean baseline stroke knowledge score was 72.4%. In a multivariate model adjusted for age, SKS was significantly associated with education (p <.0001) gender (p=.0046) and Latino race (p <.0001) with Latino males having less than high school education scoring 5 points less than white females with HS or more. While 46% demonstrated competency on the multiple choice section, only 26% demonstrated competency on open ended behavioral intent questions. Health literacy level was significantly correlated (r=.324, p=.0001) with total stroke knowledge score, but was not correlated with post-intervention competency assessment (r=.116, p=.116). Of the 76% that had a competency score, 77% demonstrated full competency post intervention.

Discussion:
Mismatch between multiple choice knowledge score and competency indicate that not all evaluation methods correspond to true learning. Appropriate intervention can overcome disparities in health literacy to improve stroke education for all.
Abstract WP18: Gender Differences In Intra-arterial Therapy
Authors: Demel Stacie , Aghaebrahim Amin , Jadhav Ashutosh , Jovin Tudor , Klein Autumn
Published: March 2022

Background:
Women have higher post-stroke mortality and rate of disability. Earlier studies have reported on difference between outcomes in men and women with regard to CEA, stenting and tPA. However, there are no studies comparing gender differences with intra-arterial (IA) treatment in patients with symptomatic intracranial stenosis.

Methods:
This retrospective study performed at an academic tertiary care facility compared men and women treated for M1 severe stenosis or occlusion with IA therapy from November 2002 to May 2011. We compared baseline premorbid conditions. Treatment outcomes included infarct size, modified Rankin Scale (mRS) and mortality. Two-tailed Fischer’s Exact Test was used for data analysis.

Results:
Of 223 patients, 105 (47.1%) were men and 113 (50.7%) were women. Women were older (64.1 vs. 67.9 years; p < 0.05). Baseline characteristics such as hypertension, atrial fibrillation and hyperlipidemia showed no significant differences between men and women (p> 0.05). NIHSS at presentation (15.5 vs 16.1; p > 0.05) and infarct size post intervention (78.6 vs 76.5 cc
3
; p > 0.05) were not different. Successful revascularization rate was 88% in women and 81% in men (p = 0.15). 56% of men but only 41% of women had a mRS ≤ 2 at 3 months. (p < 0.05). Preliminary data suggests no differences in mortality.

Conclusion:
Despite the findings that infarct size and revascularization rates were the same between men and women, women had worse functional outcomes at 3 months. In future investigations, we will identify contributing factors that may explain outcome differences between men and women.