bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract T P130: Determinants of White Matter Hyperintensity Burden Differ at the Extremes of Age of Ischemic Stroke Onset
Authors: Zhang Cathy R , Cloonan Lisa , Fitzpatrick Kaitlin M , Kanakis Allison S , Ayres Alison M , Furie Karen L , Rosand Jonathan , Rost Natalia S
Published: March 2022

Background:
White matter hyperintensity (WMH) detected on MRI scans of patients with acute ischemic stroke (AIS) is associated with greater risk of infarct progression, poor post-stroke outcomes, and recurrent stroke. Age is strongly linked to risk of stroke and WMH. We hypothesized that determinants of WMH severity differ across the lifetime and sought to test it in a prospective cohort of AIS patients with early (<55 years), late (>75 years) versus average age of stroke onset.

Methods:
Clinical characteristics as well as laboratory and radiographic data were ascertained on admission for AIS in all consecutive patients ≥ 18 years. WMH volume (WMHv) was measured using a previously validated, semi-automated method, normalized for intracranial area, and natural log-transformed for univariate and multivariate linear regression analyses.

Results:
Of 754 AIS patients, 175 (23.2%) developed early-onset (mean age 46.4 ± 7.5 years) and 237 (31.4%) late-onset (mean age 82.1 ± 5.2 years) stroke. Median WMHv differed between the early-onset AIS (2.4cc, IQR 1.6 - 4.5), late-onset AIS (11cc, IQR 5.8 - 23.2) and average-age-of-onset stroke patients (mean age 65.6 ± 5.8 years, median WMHv 6.4cc, IQR 3.2 - 13.0). In univariate analysis, WMHv burden was associated with age (p = 0.03) and history of tobacco use (p = 6.6E-3) in early-onset AIS, with gender (p = 0.03) in late-onset AIS, versus age (p = 1.8E-8) and hyperlipidemia (p = 0.045) in average-age-of-onset AIS. Although backward stepwise selection confirmed male gender (ß = -0.26, p = 0.04) in late-onset AIS patients as well as age (ß = 0.05, p = 3.9E-8) and hyperlipidemia (ß = -0.26, p = 0.02) in patients with average age of AIS onset as predictors of WMHv, only tobacco use (ß = 0.35, p = 8.8E-3) remained an independent predictor of WMHv severity in early-onset AIS patients.

Conclusions:
Phenotypic determinants of WMH severity in AIS patients differ at the extremes of age of stroke onset, including a strong link between tobacco use in patients with early-onset stroke and burden of small cerebral vessel disease. While age remains a major risk factor for WMH, modifiable determinants - such as smoking - should be targeted in the future to reduce WMH and mitigate stroke risk in each age group.
Abstract T P140: The Intriguing Metabolically Healthy but Obese Phenotype:Association With the Prognosis After Ischemic Stroke
Authors: Oh Mi-Young , Lee Hyon , Kim Min-Jung , Ko Sang Bae , Lee Seung-Hoon , Yoon Byung-Woo
Published: March 2022

Background & Objective:
“Metabolically healthy but obese phenotype” is defined as individuals with overweight or obese without metabolic complication. They seemed to be protected against obesity related morbidity, and have a lower risk for cardiovascular and all cause of mortality even than normal weighted individuals. However, the impact of this interesting subgroup on the prognosis after stroke has not been evaluated. The purpose of this study was to assess whether the metabolically healthy but obese phenotype would have a lower risk of poor outcome after stroke compared to other metabolic phenotypes

Methods:
We collected the data of 645 patients with ischemic stroke. The patients were classed as normal weight (body mass index[BMI] 18.5-22.9 kg/ m2), overweight to obese (BMI≥23 kg/ m2). The patients who met 0 or 1 of the criteria of metabolic syndrome were classified as metabolically healthy. The functional outcome was defined using modified rankin scale 3 months after the index stroke (good, grade 0 to 1 vs. poor, grade 2 to 6). Logistic regression analyses were used to examine the association between the phenotypes and poor outcome.

Results:
Among the total patients, 122 (18.9%) patients were included as “Metabolically healthy but obese” group. As “Metabolically healthy but obese group” was a referent, “Normal weight but metabolically unhealthy” (adjusted odds ratio [OR], 3.61, 95% confidential interval [CI], 1.73-7.51, p<0.01), and “Obese and metabolically unhealthy” groups were associated with poor outcome (adjusted OR 2.11, 95% CI 1.03-4.11, p=0.04). The association between “Normal weight and metabolically healthy” phenotype and poor outcome was not statistically significant.

Conclusions:
In this study, we showed that metabolically unhealthy patients, even though they had normal weight, were likely to have a threefold increased risk of poor functional outcome compared to the “Metabolically healthy but obese” patients. The metabolic status of patients should be considered with obesity itself in predicting the prognosis of ischemic stroke.
Abstract T P143: Lipid Profile Components and Subclinical Cerebrovascular Disease in the Northern Manhattan Study
Authors: Willey Joshua Z , Gardener Hannah , Moon Yeseon P , Yoshita Mitsuhiro , DeCarli Charles , Cheung Ying K , Sacco Ralph L , Elkind Mitchell S , Wright Clinton B
Published: March 2022

Objective:
Examine the association between lipid profile components and subclinical cerebrovascular disease on magnetic resonance imaging (MRI).

Design/Methods:
Fasting plasma lipids were collected on Northern Manhattan Study participants; a subsample underwent brain MRI (n=1256 with lipids available) a median of 6.2 (range=0-14) years after enrolment, when repeat fasting lipids were obtained (n=1029). We used lipid profile components at the time of initial enrollment as categorical variables, as well as change in clinical categories over the 2 measures. We examined the association between lipid profile components and (1)total white matter hyperintensity volume (WMHV) using linear regression, and (2)silent brain infarcts (SBI) using logistic regression.

Results:
The association between baseline lipids and WMHV was modified by apoE status (chi-squared with 2 degrees of freedom,p=0.03), such that among apoE4 carriers those with total cholesterol (TC)≥200mg/dl ) had a trend towards smaller WMHV than those with TC<200mg/dl (difference in logWMHV -0.19,p=0.07) while there was no difference among apoE3 carriers. A transition from low risk high-density lipoprotein cholesterol (HDL-C)(>50 mg/dl for women,>40 mg/dl for men) at baseline to high risk HDL-C at the time of MRI (versus starting and remaining low risk) was associated with greater WMHV (difference in logWMHV 0.34,p-value 0.03). We noted a similar association with transitioning to a TC≥200mg/dl at the time of MRI (difference in logWMHV 0.25,p-value 0.006) There were no associations with SBI.

Conclusions:
The association of plasma lipid profile components with greater WMHV may depend on apoE genotype and worsening HDL and TC risk levels over time.
Abstract T P148: Lactate Dehydrogenase Levels are Associated with Acute Ischemic Stroke in Ventricular Assist Device Patients
Authors: Boehme Amelia K , Dillon Chrisly , McGwin Gerald , Pamboukian Salpy V , Limdi Nita A
Published: March 2022

Background:
Patients with Ventricular Assist Devices (VADs) have an increased thromboembolic (TE) risk including a higher risk of acute ischemic stroke (AIS). To mitigate this risk patients are placed on a combination of aspirin, clopidogrel and warfarin with a goal INR of 2-3. VAD patients are at higher risk for hemolysis, which contributes to the risk for TE and AIS. We hypothesize that Lactate Dehydrogenase (LDH) elevation, a marker of hemolysis, is associated with an increased risk of AIS.

Methods:
Patients (n=98) receiving a continuous flow VAD at the University of Alabama at Birmingham between 2008 and 2012 were included in this analysis. The association of LDH levels (collected pre-VAD, VAD date, 14 days, 1 month, 3 months, 6 months, 9 months and 12 months after VAD) with AIS was evaluated using time-to-event-analysis adjusting for comorbid conditions, age at implant and antithrombotic therapy.

Results:
The median age at implant was 53 (20-76) with 78% patients male, 64% white and 59% serving as a bridge to transplant. The incidence of AIS was 13 events/100 patient years (95% CI 6.85-22.6). No patients received IV t-PA or intraarterial therapy. Patients with elevated LDH (>500) at VAD implant (Figure) were at greater risk for AIS with the association becoming stronger after adjustment (Hazard Ratio (HR) 31.1, 95% CI 0.61-1577, p=0.0863). Elevated LDH at 30-days post VAD implant was associated with a higher risk of AIS, even after adjustment (HR 12.3, 95% CI 1.12-134.9, p=0.0403).

Conclusion:
AIS is common among VAD patients despite their antithrombotic regimen. Early elevation of LDH is associated with increased risk of AIS. However, even elevation of LDH on the day of VAD implant appears to be associated with increased AIS risk, indicating non-VAD related LDH elevation may identify a high risk subgroup. Since these patients have contraindications to the standard AIS treatments, identifying predictors, such as LDH, of AIS and preventing AIS are of interest.
Abstract T P151: Fibroblast Growth Factor 23 and Carotid Plaque: the Northern Manhattan Study (NOMAS)
Authors: Shah Nirav , Dong Chuanhui , Cespedes Sandino , Elkind Mitchell S , Sacco Ralph L , Wolf Myles , Rundek Tatjana , Wright Clinton B
Published: March 2022

Introduction:
Fibroblast growth factor 23 (FGF23), a hormone that regulates phosphate homeostasis, has recently been linked with mortality, cardiovascular events, and stroke. While limited evidence suggests that FGF23 is associated with arterial calcification in chronic kidney disease (CKD), data on the association between FGF23 and carotid plaque are lacking, especially in population-based studies. This study aimed to determine if relative elevations of FGF23 are associated with presence and area of carotid plaque in a race/ethnically diverse community-based sample.

Methods:
There were 1,512 stroke-free NOMAS participants with FGF23 levels and 2D carotid ultrasound data available (mean age, 68±9; 61% women; 62% Hispanic, 18% black, 18% white, 2% other). We evaluated the association of FGF23, continuously and by quintiles, with presence of carotid plaque using logistic regression models and with plaque area (cubic root transformed) using linear regression models, adjusting for age, sex, race/ethnicity, estimated glomerular filtration rate (eGFR), body mass index, smoking, alcohol use, blood pressure, fasting glucose, lipids, and hypertension, diabetes, and dyslipidemia medication use.

Results:
Participants with FGF23 levels in the top quintile had greater odds of having carotid plaque (OR=1.5 95% CI=1.0-2.2, p=0.04) and larger plaque area (beta=0.3, 95% CI=0.1-0.5, p=0.006) than those in the lowest quintile, adjusting for eGFR and demographic factors, although the association was attenuated after adjusting for vascular risk factors. Linear regression models also showed that log transformed FGF23 was associated with greater plaque area adjusting for eGFR and sociodemographic factors (beta=0.2, 95% CI=0.03-0.3, p=0.02), and this remained marginally significant after adjusting for vascular risk factors (beta=0.1, 95% CI=0.0-0.3, p=0.05).

Conclusions:
These data suggest that FGF23 is associated with the likelihood and burden of carotid atherosclerosis in a stroke-free community based sample. Our finding that the association between FGF23 and carotid plaque measures was weaker after adjusting for vascular risk factors suggests possible mediation and requires further study.
Abstract T P165: Prospective Screening of Family Members With Moyamoya Disease Patients
Authors: Duan Lian
Published: March 2022

Background:
Genetic factor plays an important role in the pathogenesis of moyamoya disease (MMD). Previous studies concentrated on the familial patients. In this study, we focus on the family members of sporadic MMD patients, and aim to gain a clearer understanding of the role that genetic factor plays in MMD.

Methods:
The immediate family members of MMD patients were initially screened by Transcranial Doppler Sonography (TCD) and the positive cases were verified by Magnetic Resonance Angiography (MRA). A total of 285 immediate family members of 245 sporadic MMD patients (2011.07-2013.03) were screened.

Results:
33 cases were confirmed positive at 11.6% detection rate. 21 cases (from 20 index MMD patients) was validated by MRA. As a result, the proportion of familial MMD patients in our hospital increased from 7% (38/527) to 15% (79/527) in this period. For the main segments of the circle of Willis, which include the anterior cerebral arteries (ACA), middle cerebral arteries (MCA) and posterior cerebral arteries (PCA), the accordant rate between TCD and MRA was 95% (91/96). Kappa values for ACA, MCA and PCA were 0.91, 0.72 and 0.47 respectively. The familial cases confirmed by our screening showed a significant higher percentage of asymptomatic patients (57%) comparing to the 9% from the 38 familial MMD patients who had a clear family history before.

Conclusions:
Familial MMD patients may account for a higher percentage among all cases than previously thought. Some of the family member of MMD patients may also have MMD but present with asymptomatic. A routine screening should be implemented for all family members of MMD patients to improve the detection rate for this part of patient base. TCD has a high diagnostic agreement with MRA for MMD. By contrast, TCD may be a preferred choice for screening, because it’s inexpensive and safe.
Abstract T P166: Cerebral Infarction Occurrence in Settings of Acute Traumatic Injury. Analysis of a Prospective Multicenter Trial
Authors: Adil Malik M , Mohindroo Tanya , Minhas Sheharyar , Qureshi Adnan I
Published: March 2022

Background:
Acute ischemic stroke can be seen in the settings of acute traumatic injury. However, the rates of and factors associated with cerebral infarction occurrence in trauma setting are not well understood.

Methods:
We analyzed data from multicenter, randomized, blinded clinical trial conducted at 114 emergency medical services agencies in North America within the Resuscitation Outcomes Consortium. Initial resuscitation fluid, 250 mL of either 7.5% saline per 6% dextran 70 (hypertonic saline/dextran, HSD), 7.5% saline (hypertonic saline, HS), or 0.9% saline (normal saline, NS) administered by out-of-hospital providers. Injured patients, age ≥ 15 years with hypovolemic shock or those with blunt trauma and a prehospital Glasgow Coma Scale score of ≤8 were included. Cerebral infarction during hospitalization was one of the data ascertained at three time points: within 24 hours, within 7 days, and within 28 days.

Results:
Of the 1282 patients recruited, 34 developed cerebral infarction (3 <24 hrs, 25 <7 days, and 6 < 28 days). The proportion of patients with injury severity score> 26 was higher among patients with cerebral infarction (79.4% versus 45.0%, p=<.0001). The mean admission systolic blood pressure (±SD) was similar between those who did or did not develop cerebral infarction (134.1±27.6 versus 139.2±33.3, p=0.2). Patients who developed cerebral infarction were more likely to have mass lesions on initial CT scan (53% versus 15.7%, p<0.0001). A higher proportion of patients required craniotomy within 24 hrs among those who developed cerebral infarction (55.8% versus 10.8%, p=<0.0001). The 28 day survival was significantly lower among patients who developed cerebral infarction (44.1% versus 76.3%, p<0.0001). Among patients who developed cerebral infarction had a significantly higher proportion of Glasgow Outcome Scale of ≤4 (87.8% versus 56.8%, p<0.0004) at 6 months. The proportion of patients with vegetative state or death was higher among those patients with cerebral infarction (5.8% versus 1.3%, p<0.03).

Conclusions:
Cerebral infarction can be infrequently seen in the settings of acute traumatic injury particularly in patients with mass lesions requiring craniotomy.
Abstract T P169: The Questionable Cost-effectiveness of Hypercoagulable Testing in Arterial Ischemic Stroke
Authors: Kohler Scott J , Southerland Andrew M , Worrall Bradford B
Published: March 2022

Introduction:
Hypercoagulable states may be associated with arterial ischemic stroke, particularly in cryptogenic stroke and incidence in the young. Prior studies identify an association with arterial stroke of antiphospholipid antibody syndrome and hyperhomocysteinemia, possible association of Factor V Leiden and Prothrombin mutation, and little or no association of Protein C, Protein S, and Antithrombin III deficiencies. Little data exists regarding the cost-effectiveness of routine testing in selected cases.

Hypothesis:
Routine hypercoagulable testing at our institution rarely changes management and a selected testing approach is more cost-effective.

Methods:
Based on known associations of hypercoagulable states with acute ischemic stroke, we created a revised testing criteria to exclude states (1) primarily associated with venous occlusion and (2) unlikely to change medical management in secondary stroke prevention. As part of a quality assurance review, we retrospectively applied these criteria to 94 stroke patients who consecutively received the hypercoagulable panel over 2 years.

Results:
Assuming current costs of hypercoagulable testing at our institution, a potential $120,000 in health care costs could potentially have been saved with no additional diagnostic value and the same outcome on medical management for secondary stroke prevention.

Conclusion:
A selected testing criteria for hypercoagulable states in diagnosis of arterial ischemic stroke may be more cost effective. Further prospective study in select stroke cases is warranted.
Abstract T P178: Echocardiographic Left Atrial Strain Analysis Plus NT-ProBNP to Determine Cardioembolic Strokes
Authors: Pagola Jorge , Bustamante Alejandro , Gonzalez Alujas Teresa , Sero Laia , Flores Alan , Muchada Marian , Rodriguez-Luna David , Sanjuan Estela , Meler Pilar , Rubiera Marta , Ribo Marc , Alvarez-Sabin Jose , Evangelista Arturo , Montaner Joan , Molina Carlos A
Published: March 2022

Background:
Undetected paroxistic atrial fibrillation (PAF) is the main etiology of undetermined ischemic strokes. The left atria functionality assessed by echocardiography Strain analysis (LA-S) is lower in patients with PAF. N-terminal pro-brain natriuretic peptide (NT-ProBNP) has been described as a marker of cardioembolic etiology. We describe the relationship between these surrogates in order to improve the detection of strokes related to PAF.

Methods:
Consecutive undetermined acute stroke patients underwent specific echocardiography study to determine the LA-S by speckle tracking analysis. All patients were monitored by implantable Reveal TX Holter during three years. In those who were not detected PAF (NO PAF GROUP, n=20) were compared with PAF detected patients. PAF GROUP were defined as those PAF detected patients (n=2) plus acute stroke patients with previously known PAF (n=41). A LA-S cut off point of -3.62% was defined to predict the sensitivity and specificity of PAF detection. NT-proBNP was measured in a group of 25 non AF patients (pro-BNP group) with suspected cardioembolic stroke and these values were compared between patients with predefined high (>3.62%) and low (<3.62%) LA-S.

Results:
There were no differences in the baseline variables (PAF group vs NO PAF group). PAF group showed a percentage of LA -S significantly lower in the anterior- posterior walls (-2% +/- 1.76 vs -6.9+/-7.45) (p=0.035). LA -S cut off value of -3.62% predicted PAF with a sensitivity of 77% and specificity of 80%. According pro-BNP group those patients with low SL-LA had a trend to a higher NT-ProBNP value compared with high SL-LA group (685 vs 293 pg/mL; p=0.07). There were no differences in the size of the atria between the groups.

Conclusions:
Measurement of LA-S and NT-ProBNP in patients with undetermined stroke could be a useful tool to select those patients that could benefit from long-term cardiac monitoring in order to diagnose PAF.
Abstract T P180: Diastolic Dysfunction and Left Atrial Volume Mediates Embolic Stroke in Patients with Atrial Fibrillation
Authors: Alhaji Mohammad , Raju Mahesh , Al Darazi Fahed , Kakkar Amit , Olstein Richard , Prabhakaran Shyam , Doukky Rami
Published: March 2022

Background:
Several risk predictors for stroke in AF patients, specifically the CHADS2 criteria, have been implicated in left ventricular (LV) diastolic dysfunction (DD). It is plausible that DD and subsequent elevation in left ventricular filling pressure (LVFP) mediate stasis within the left atrium leading to thrombus formation and embolic stroke in AF patients. Left atrial volume index (LAVI) is known to correlate with LVFP and AF chronicity. We sought to assess whether LAVI can predict ischemic stroke in patients with AF, independent of clinical risk predictors.

Hypothesis:
In AF patients, LAVI is associated with ischemic stroke independent of clinical covariates.

Methods:
We conducted a retrospective case-control study with 203 patients. The case group (n=33) was derived from our institution’s stroke database which was used to identify strokes attributed to an embolic mechanism related to AF as adjudicated by expert neurologist. The control group (n=79) was generated of consecutive AF patients without previous history of stroke. The left atrial dimensions were measured and the left atrial volume (LAVI) was calculated. Binary logistic regression analysis was used to explore whether LAVI predicted stroke independently from CHADS2 score.

Results:
The mean LAVI in the stroke group was 50.74 s 23.83 in the non-stroke group (p<0.001). Binary logistic regression analysis demonstrated that LAVI was significant as an independent risk factor in addition to the CHADS2 score (OR 1.12, CI: 1.0-1.185 per cc/m2 of volume increment, p<0.001). Subsequently, we developed a novel risk score in which 1 additional point was added to the CHADS2 score for every 5cc increment in the LAVI. The receiver operator characteristics curve analysis showed that the AUC for the novel risk score (LAVI +CHADS2) as a predictor for ischemic stroke to be 0.87 vs 0.74 for the clinical factors alone (p<0.05)

Conclusion:
Our preliminary data demonstrates that LAVI is an independent risk predictor for embolic stroke in patients with AF. Integrating LAVI with clinical predictors (CHADS2 score) may enhance our ability in predicting stroke and to allow us to better select patients for anticoagulation therapy.
Abstract T P196: The Feasibility of iPad Technology for Remote Stroke Assessment Within a Moving Ambulance
Authors: Hatzigeorgiou Marianthi N , Rao Pavan , Litchin Nicholas , Carroll Jeanne , Khatri Rakesh , Chang Fen-Lei F
Published: March 2022

Several regional telestroke systems now exist to remotely assess stroke patients at community hospitals via wireless technology in order to decrease the time between stroke onset and treatment. More recently, mobile applications have been studied yet the wireless technology was not sufficient to support reliable audiovisual transmission. This study assessed the feasibility of remote stroke assessment via an iPad within a moving ambulance. Connectivity, quality of transmission, and interrater agreement were examined. Using routes between five spoke rural community hospitals and a telemedicine hub hospital in Fort Wayne, Indiana (radius of approximately 45 miles), two blinded, certified NIH Stroke Scale (NIHSS) raters conducted 30 stroke assessments on a standardized patient. An iPad was mounted within an ambulance and the standardized patient was examined by both in-person and remote assessors. The study demonstrated feasibility in 84% of the assessments with kappa coefficient analysis demonstrating strong interrater agreement for subscales with the exceptions of Best Language and Motor Right Leg. The assessors’ total NIHSS scores were found to have an 88% agreement to the expected scores. When compared to the expected NIHSS scores, subscales showed strong agreement, except moderate agreement in the Best Language subscale. The results of this feasibility study demonstrate that remote NIHSS assessments based within a moving ambulance were feasible. This success rate supports further study of the application in a real, live clinical setting.
Abstract T P201: Sequential Treatment With Minocycline and Candesartan Improves Long Term Recovery After Stroke
Authors: Soliman Sahar , Ishrat Tauheed , Patel Ami , Fouda Abdelrahman , Ergul Adviye , Fagan Susan
Published: March 2022

Minocycline—a tetracycline antibiotic with anti-inflammatory and MMP inhibitory effects—has been promising in stroke preclinical as well as phase I and II clinical trials. Candesartan- angiotensin II receptor blocker- improved outcome and enhanced neovascularization post stroke. Despite its failure to provide benefit in the SCAST trial, candesartan’s long history of success in preclinical studies leads us to further investigate the combination of candesartan with other promising agents in the management of ischemic stroke.

Objective:
We propose the combination of candesartan and minocycline as a potential treatment for ischemic stroke and we optimize the timing of administration for maximal benefit. We hypothesize that early minocycline administration- to reduce inflammation- followed by 7-day candesartan dosing- to stimulate angiogenesis- yields a better outcome than either alone. Due to opposing actions of both agents on MMPs, sequential rather than simultaneous administration maintains candesartan neovascularization potential.

Methods:
Wistar rats subjected to 90-minute middle cerebral artery occlusion (MCAO) were divided into 4 groups: Saline, Candesartan, Minocycline and combination. Neurobehavioral tests were performed 1, 3, 7 and 14 days after stroke. Brains were collected on day 14 for assessment of angiogenesis and infarct size. Human brain endothelial cell proliferation and tube formation were measured
in vitro
by BrdU incorporation and Matrigel tube formation assays.

Results:
Sequential therapy improved neurobehavioral outcome and infarct volume compared to saline or either treatment alone. When added after minocycline, candesartan was effective at stimulating angiogenesis. However, simultaneous treatment decreased endothelial cell proliferation and tube formation
in vitro
.

Conclusion:
Sequential rather than simultaneous treatment with candesartan and minocycline offers more benefit than either alone.
Abstract T P202: Crosstalk Between Microglia and T Cells Mediated by FasL After Cerebral Ischemia
Authors: Ye Dan , Chen Xiang , Xu Yun
Published: March 2022

Background:
Inflammation is closely implicated in the pathogenesis and outcome of ischemic stroke. Although crosstalk between microglia and T cells has been studied in CNS diseases such as Parkinson’s disease, yet few research has focused this relationship on stroke, and no definite mechanism has been proposed to explain the relationship. In this study, we discussed the crosstalk between microglia and T cells and the probable role of FasL in the progress.

Methods:
Primary microglia were extracted from the cortexes of new born C57BL/6J (B6) mice while primary T cells were extracted from spleens of adult B6 mice. MCAO and OGD model were used to mimic cerebral ischemic injury in
vivo
and in
vitro
respectively. T cell chemotaxis assay was determined by transwell system. Cell markers in
vivo
were detected by immunofluorescence. The expression of cytokines were detected by Q-PCR. The amount of soluble FasL into the cultured media were measured by ELISA.

Results:
In
vivo
, T cells infiltrated into the ischemic lesions and aggregated around microglia within 24 h after MCAO. The expression of FasL in microglia was also up-regulated after MCAO. However, in FasL mutant (
Gld
) mice, the infiltration and aggregation of T cells were induced. In
vitro
, when coculturing primary T cells with primary microglia, crosstalk also existed between them morphologically after OGD. Furthermore, proinflammatory cytokines such as IL-1β, IL-6 were increased and anti-inflammatroy cytokines such as IL-10 were reduced by Q-PCR. However, the crosstalk wasn’t obvious in
Gld
primary cocultured cells. On the other hand, soluble FasL was increased in the supernatant of activated microglia by ELISA. In chemotaxis assay, T cells were chemotactic to supernatant of activated microglia while the effect was weakened after inhibiting FasL or MCP-1, which indicating that soluble FasL released by microglia may also play an important role in chemoattracting T cells.

Conclusions:
These data suggest that an inflammatory crosstalk take place between activated microglia and T cells after cerebral ischemia, in which FasL may play an important part. Microglia may chemoattract periphery T cells by releasing soluble FasL after ischemic injury.
Abstract T P203: Areas of Cerebral Ischemia Have Increased Propensity to Convert to Infarct Among Diabetics
Authors: Mohamed Wazim , Reddy Sanath Kasi , Bhattacharya Pratik
Published: March 2022

Diabetes influences ischemic stroke outcome. While several theories are proposed, the mechanism for worse outcomes is unclear. Perfusion computed tomography (PCT) helps identify stroke patients who would benefit from endovascular therapy. Our hypothesis was that PCT could potentially be used to elucidate the biological basis of poor outcomes among diabetics with stroke

Methods:
Patients with ischemic stroke that underwent PCT at admission from August 2011 to March 2012 were reviewed. PCT protocol included 4 supratentorial slices, 8mm thick. Areas of increased mean transit time(MTT) were traced and marked as ischemic area. Area of preserved cerebral blood volume(CBV) was penumbra. CBV and MTT were compared among diabetics and non-diabetics.

Results:
The study included 44 patients: 15 diabetic and 29 non-diabetics. The age, sex, race distributions and NIH stroke scale in both groups were similar. There were no differences in risk factors such as hypertension, atrial fibrillation and smoking. The average MTT was similar for both groups in the ischemic area (8.1ml/100g in diabetics and 8.7ml/100g in non diabetics, p=0.43) and within penumbra (8.4ml/100g in diabetics and 9.2 in non diabetics, p=0.32). The CBV was significantly lower among diabetics within the ischemic area (2.8sec vs.3.5sec among nondiabetics, p=0.04) as well as penumbra (2.8sec vs. 3.6sec in nondiabetics, p=0.03). This suggests an increased propensity for penumbra to convert to infarct among diabetics. In conclusion, PCT evaluation suggests that a lower CBV could explain worse outcomes among diabetics with stroke. Microvascular disease and endothelial dysfunction should be investigated as potential mechanisms for lower CBV and worse outcomes among diabetics.
Abstract T P217: Neuroprotective Effects of Cilostazol through the Multi-mechanisms in Mice Permanent Focal Ischemia
Authors: Shichinohe Hideo , Yamauchi Tomohiro , Saito Hisayasu , Abumiya Takeo , Houkin Kiyohiro , Kuroda Satoshi
Published: March 2022

Background and Purpose:
It has been reported that Cilostazol, which is phosphodiesterase (PDE) 3 inhibitor clinically used as an antiplatelet drug, could ameliorate ischemic brain injury, but the mechanisms were not clarified. We aimed to investigate how Cilostazol affected mice permanent focal ischemia model.

Methods:
Male Balb/c mice were subjected to permanent middle cerebral artery (MCA) occlusion. They were treated with Cilostazol (10- mg/kg or 20- mg/kg) or vehicle 30 min and 24 h post-ischemia. Infarct volume was assessed by 2,3,5-triphenyltetrazolium chloride (TTC) method after 48 h (n=8 in each group). In histological analysis, the animals were sacrificed 6 h or 24 h post-ischemia (n=5 in each group), and then the immunohistochemistry was performed to the brain sections.

Results:
We showed that the treatment with Cilostazol salvaged the tissue damage in the infarct rim in a dose-dependent manner, and 20- mg/kg Cilostazol significantly reduced infarct volume to 70.1±24.4% of the control (P<0.05). Immunoreaction for 8-Hydroxydeoxyguanosine (OHdG), an oxidative stress marker, showed the neuronal damage by oxidative stress in peri-infarct, and the treatment with Cilostazol reduced the ratio of the damaged neurons 6 h post-ischemia (65.8±33.5% in vehicle-treated animals, 21.3±9.9% in Cilostazol-treated ones, P<0.05). Double staining for 8-OHdG and von Willebrand factor also showed that Cilostazol attenuated oxidative stress on the endothelial cells in peri-infarct 24 h post-ischemia, significantly (P<0.01). On the other hand, the immunostaining for phosphorylated cAMP response element binding protein (pCREB) showed that Cilostazol increased the ratio of the pCREB-positive neurons in peri-infarct 24 h post-ischemia significantly (74.5±8.0% in vehicle-treated animals, 93.6±2.9% in Cilostazol-treated ones, P<0.01).

Conclusions:
These findings suggested that Cilostazol could have multi-mechanisms to ameliorate tissue damage due to permanent focal cerebral ischemia. Thus, one is to attenuate oxidative stress on neurnons and endothelial cells in the infarct rim, and another is to protect neural damage with anti-apoptotic effect through the pathway of Akt/pCREB.
Abstract T P221: Effect of CD4 And CD8 T Lymphocytes on Infarct Volume Following Experimental Stroke in Male Splenectomized Mice
Authors: Wang Jianming , Bodhankar Sheetal , Yu Xiaolin , Offner Halina , Murphy Stephanie J
Published: March 2022

We have previously shown profound splenic activation by 6 hours following experimental stroke, resulting in rapid and widespread increased production of inflammatory factors by basal and activated splenocytes in male mice. Our lab and others have also shown a subsequent extensive loss of lymphocytes and increased lymphocyte apoptosis in spleen 12 hours after experimental stroke. Lastly, we and others have shown that splenic immunocytes can contribute to increased brain inflammation and infarct volume. However, it is unclear which splenic immunocyte populations may contribute to the evolving ischemic brain injury. Using a mouse splenectomy model and adoptive cell transfer protocols, we evaluated the effect of different splenic immunocyte populations, specifically CD4 and CD8 T lymphocytes, on infarct volume. Male C57BL/6J mice were splenectomized 14 days before experimental stroke and treated 24 hours before experimental stroke with either vehicle (saline), CD4 T lymphocytes, or CD8 T lymphocytes obtained from GFP reporter mice. Each mouse (n=8-10 per group) then underwent 60 minutes of middle cerebral artery occlusion via intraluminal filament. All mice were euthanized and brains collected at 96 hours of reperfusion. Infarct volume (% corrected contralateral structure) was determined by image analysis of coronal brain slices stained with 2,3,5-triphenyltetrazolium chloride. Adoptive transfer of GFP

positive CD4 (cortex, 44±3%; striatum, 50±2%) or CD8 (cortex, 48±2%; striatum, 53±3%) T lymphocytes in splenectomized male mice did not alter infarct volume compared to vehicle-treated (cortex, 38±4%; striatum, 42±5%) splenectomized males (cortex, p=0.140; striatum, p=0.143). Although adding back CD4 or CD8 T lymphocytes did not appear to alter infarct volume, these immunocyte populations are comprised of both inflammatory and regulatory subtypes. Thus, future studies will evaluate the effect of different CD4 and CD8 subpopulations on ischemic brain outcomes. This study was supported by National Institutes of Health grant NS076013.
Abstract T P223: Role of GSK-3ß and Transforming Growth Factor-ß-activated Kinase in Ischemic Neuroprotection
Authors: Venna Venugopal R , Benashski Sharon E , McCullough Louise D
Published: March 2022

Objectives:
Glycogen synthase kinase-3β (GSK-3β) is involved in several essential intracellular signaling pathways involved in both cell survival and cell death. GSK-3β activation promotes inflammation and apoptosis which are detrimental in stroke. GSK-3β inhibition enhances cognition in many animal models; however the role of GSK-3β in stroke and the mechanism by which activation is detrimental remains to be elucidated. It was recently found that GSK inhibits the function of the master energy sensor AMP-activated kinase (AMPK). We have also recently shown that TAK1, an upstream kinase that activates AMPK, is also involved in regulating ischemic injury. Inhibition of TAK leads to dramatic protection, even when treatment is delayed, and this effect is independent of AMPK signaling. We hypothesize that TAK1 regulates GSK-3β. The aim of this study was to determine whether GSK-3β inhibition confers ischemic neuroprotection via TAK1 signaling.

Methods:
C57BL/6 male mice were randomly assigned to treatment groups and subjected to right middle cerebral artery occlusion The GSK-3β inhibitor VIII (4 mg/kg); and/or the TAK1 inhibitor, 5Z-7-oxozeaenol (5 mg/kg) were administered i.p. either immediately or 2h after stroke. Control mice were treated vehicle. Western blotting was performed for on brains obtained 6h after stroke. Data were presented as mean ± SEM.

Results:
GSK-3β inhibition was protective when delivered immediately after stroke (Total hemisphere: 44.2±3.2 vs 36.2±3.1; n=8, p<0.05) or if treatment was delayed for 2h (Total: 46.2±3.0 vs 32.2±4.3; n=7, p<0.05). Beneficial effects of GSK-3β inhibition in NDS (p<0.05) was also seen. TAK inhibitor reduced pTAK1 in parallel to GSK-3β inhibition. But, GSK-3β inhibitor treated brains has no effect on pTAK1 levels p>0.05. Finally, compared to GSK-3β inhibition alone, simultaneous GSK-3β+TAK1 inhibition did not offer any additional neuroprotection in stroke (Total: 33.6±2.8 vs 30.7±3.9; p>0.05).

Conclusion:
Our findings indicate that GSK-3β inhibition is protective even with delayed administration after stroke. In this study, we identified TAK1 as a potential upstream regulator of GSK-3β. Directly targeting TAK1 and GSK-3β inhibition may develop into a novel and powerful neuroprotective strategy.
Abstract T P224: A Canine Model of Acute Segmental Vertebral Artery Embolism
Authors: Zhang Yunfeng , Du Bin , Jiang Weijian
Published: March 2022

BACKGROUND:
Limited availability of suitable animal model of cerebrovascular thrombosis has hampered the study of mechanical thrombectomy and clot retrieval therapies. To facilitate endovascular interventional evaluations, this study aims to develop an animal model of acute occlusion in canine vertebral artery (VA). We developed a technique for site-specific placement of a thrombus in canine model for the purpose of evaluating methods of mechanical thrombectomy and clot retrieval that allows visualization of dislocation or fragmentation of the thrombus during angiographic manipulation.

METHODS:
Angiography and embolization with a preformed thrombus was performed in 6 canines. Bilateral femoral artery puncture were performed. Under fluoroscopic guidance, an embolism protection device (EPD) was anchored to the middle segment of the left vertebral artery via the left femoral arterial sheath. A preformed radiopaque clot was injected through the guide catheter into the left VA, via contralateral femoral artery, proximal to the EPD. After 15 min of occlusion, the EPD was removed and persistent occlusion of the VA was documented angiographically.

RESULTS:
Angiography performed during the observation period confirmed persistence of VA occlusion in each case. Each VA was occluded angiographically and radiopaque clots were not found displaced during the 3-hour observation period. The setting allowed selective embolization of targeted vessels without thrombus fragmentation. Recanalization to the occluded artery was not observed in all of the arteries. Histologic evaluation revealed no intimal damage caused by the thrombus or contrast agent washout.

CONCLUSION:
We demonstrated, for the first time, a canine model of post circulation embolism induced by the autologous blood clot placement. This model can be rapidly formed, easily operated, and site controlled. This new technique may be beneficial for preclinical evaluation of thrombectomy devices in acute cerebrovascular stroke.
Abstract T P226: Novel Technique of Minimally Invasive Image Guided Catheter Evacuation of Spontaneous Basal Ganglia Hemorrhages Results in Improved Hemorrhage Evacuation and Outcome
Authors: Hawksworth Shane A , Caron Jean Louis R
Published: March 2022

Introduction:
Minimally invasive surgical (MIS) therapies demonstrate promising results in the treatment of intracerebral hemorrhages (ICH). We applied a novel technique of image guided catheter placement and evacuation, followed by recombinant tissue plasminogen activator (rtPA) thrombolysis, to treat spontaneous basal ganglia hemorrhages. We hypothesized that MIS ICH evacuation would result in decreased clot size, improved survival, and improved functional outcome. We predicted that the corticospinal tracts would be preserved, as quantified with diffusion tensor imaging (DTI).

Methods:
We reviewed a prospective series of 19 patients, selected from 655 ICHs evaluated from 2009-2013. We chose patients with an ICH volume of 10 to 80cc, age less than 80, and admission GCS greater than 5 for this procedure. Patients with aneurysms, malformations, or traumatic hemorrhages were excluded. Using frameless stereotaxy (StealthStation® AxiEM™) a 14 French, urethral rubber catheter (Bard Inc.) was guided to the clot and it was evacuated. A drainage catheter placed in the hemorrhage allowed for rtPA thrombolysis and drainage post-operatively.

Results:
Reduction in average hematoma volume from 44 +/- 16 to 26 +/- 16 cc was achieved at surgery (p<0.05). This volume was reduced to 13 +/- 8 cc after rtPA lysis and drainage (p<0.05). 30 day mortality was 10.5%, better than the 40% mortality predicted by the calculated individual ICH scores. The mean discharge GCS of 12.1 +/- 2.2 improved from the admission GCS of 9.8 +/- 2.2 (p=0.0053).

DTI of 13 patients before and after surgical evacuation demonstrated less of a decrease in the mean fractional anisotropy ratio of the ipsilateral over the contralateral corticospinal tract to the hemorrhage for those patients with discharge GCS>12 (-0.09 vs. -0.40, p=0.083). This trend did not correlate with a significant improvement of the contralateral upper extremity NIH motor score from admission to discharge for these patients (+0.6 vs. -0.40, p=0.10).

Conclusions:
Our innovative MIS technique for ICH evacuation is safe and effective. DTI demonstrates a trend towards preservation of the corticospinal tract, which may contribute to the benefits of MIS techniques over traditional craniotomy.
Abstract T P229: Expression of ECM-associated Genes in Rat Brains Following Experimental Intracerebral Hemorrhage
Authors: Yang A-Li , Cui Han-Jing , Zhou Hua-Junn , Tang Tao
Published: March 2022

Background and purpose:
Intracerebral hemorrhage (ICH) is a critical subtype of stroke. Destruction of blood brain barrier, formation of brain edema, are closely relevant to the change of extracellular matrix (ECM). The study is to investigate expression of ECM-associated genes, to provide new clues and ideas for exploring ICH treatment.

Methods:
This study was divided into two parts. (1) ICH was induced by injecting type VII collagenase. Gene chip technology was used to detect genes related with ECM. (2) Laser confocal scanning microscopy was used to observed angioarchitecture and blood perfusion after fluorescein isothiocyanate (FITC)-dextran injection. Immunohistochemisty were used to identify proliferating cell nuclear antigen (PCNA)+/ von Willebrand factor+(vWF) nuclei, and the spatiotemporal distribution of collagen I, collagen III, collagenIV,MMP-2, MMP-9, MT1-MMP, integrin αvβ3 and integrin α5β1. The protein level of collagens,MMPs, integrin β3 and integrin α5 were evaluated by Western blot.

Results:
Gene chip detection showed that ECM-related genes like most members of collagens, MMPs, intergrins have all Changed after ICH. FITC-dextran perfusion showed that the impaired blood perfusion around the hematoma increasd from 7 days to 21 days after ICH (P<0.01). Immunohistochemisty displayed that PCNA+/ vWF+ nuclei peaked at 14 days after ICH (P<0.01). Numerous collagens, MMPs or integrins -positive blood vessel could be detected around the hematoma. Western blot showed that the protein of collagens, MMPs, integrin β3 and integrin α5 all increased significantly at 4 days after ICH (P<0.05). Expression of collagenI and collagen III peaked at 14 days (P<0.05), while expression of collagen IV started to reduce from 14 days. Protein level of MMP-9 decreased from at 7 days (P<0.05), while the expression of MMP-2, MT1-MMP,integrin β3 and integrin α5 increased untill 14 days (P<0.05).

Conclusions:
Expression of ECM-related genes changed after ICH, which suggested that altered interaction between cerebral microvessel and ECM following ICH can affect angiogenesis and brain tissue restoration.

Grants from NSFC (Grant Nos. 30873221, 81173175 and 81202625) and Project for New Century Excellent Talents (NCET-11-0522).
Abstract T P245: Time to Percutaneous Endoscopic Gastrostomy (PEG) Placement and National Institutes of Health Stroke Scale (NIHSS) Correlations in Acute Ischemic Stroke (AIS)
Authors: Bajkiewicz Christopher T , Afshar-Clarkson Katherine , Olson Lindsay , Berger Lynn , Richetts Renee
Published: March 2022

Purpose:
American Heart Association 2013 guidelines for AIS management emphasize the use of PEG feeding for patients who cannot take solids/liquids orally and a 2-3 week preference for NG after stroke onset. Recent studies suggest 14-28 days before a PEG is placed. Concerns about shortened time-intervals between AIS and PEG placement have arisen, possibly averting rehabilitation of a patient capacity to swallow. High NIHSS scores may be predictive of a patient need for PEG placement. The pilot study was to investigate PEG placement timing and correlation of the NIHSS in patients admitted with AIS in a 5-campus hospital system.

Methods:
Adult patients (18-99yrs) with AIS ICD-9 primary discharge codes, correlated with PEG placement procedural codes, and NIHSS scores Sept 2012 to Jun 2013. All patients were determined unable to safely swallow, requiring enteral feeding prior to discharge. Patients with chronic dysphagia, previous PEG, traumatic brain injury, intracranial/subarachnoid hemorrhage were excluded. Retrospective chart audit of 56 cases initially identified, 22 final AIS patients had PEG placement for dysphagia prior to hospital discharge with NIHSS documentation.

Results:
Final cohort statistics: 7 females (32%) and 15 males (68%); mean patient age 78.9 years, median of 78.5 years. Mean number of days between acute onset/admission and PEG placement 12.1 days, median of 7.0 days. Mean admission NIHSS scale was 16.6 points, median 17.5 points. Mean NIHSS score at PEG placement was 19.5 points, median 21 points. 16 patients (72.7%) with NIHSS of 14 points or greater, a score previously correlated with poor long-term rehabilitation outcomes. Comparison of admission NIHSS to NIHSS at the time of PEG placement, 13 patients (59%) had an equal or increased score.

Conclusions:
Significantly shorter PEG interval times than currently recommended were noted, with high NIHSS. Current rationales are not well understood. Further research is needed to insure ‘allow for swallow’ recovery in the dysphagic AIS patient while mitigating risk of malnutrition and aspiration.