bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract TP179: Key Factors Associated with Major Depression in a National Sample of Stroke Survivors
Authors: Towfighi Amytis , Markovic Daniela , Ovbiagele Bruce
Published: March 2022

BACKGROUND:
Depression is a strong emerging independent risk factor for vascular brain injury. Up to a third of stroke survivors are depressed at any time, putting them at risk for sub-optimal recovery and recurrent vascular events. Identifying factors associated with depression after stroke in a nationally representative sample may provide insights into avenues for implementing potential population-based interventions to improve stroke outcomes.

METHODS:
We assessed factors associated with depression among adults (≥20 years) with self-reported stroke who participated in NHANES 2005-2010. Depression was identified using a Patient Health Questionnaire-8 (PHQ-8) score ≥10. The following potential predictors of depression were assessed using a random forest model: age, sex, race/ethnicity, income to poverty index ratio, education level, marital status, body mass index (BMI), smoking, history of congestive heart failure, myocardial infarction (MI), coronary artery disease, angina pectoris, diabetes, emphysema, chronic bronchitis, liver disease, and cancer. All estimates were weighted to obtain nationally representative estimates.

RESULTS:
Among stroke survivors in NHANES 2005-2010 (n=678), 546 completed the PHQ-8 survey. Of those who completed the survey, 17% had depression, corresponding to 872,237 stroke survivors in the US with depression. Compared to stroke survivors without depression, depressed individuals were younger (55.0 vs. 65.8 years), more likely to have an income to poverty ratio <200% (70% vs. 44%) and more likely to smoke (50% vs. 19%; all p<0.05). The following 10 factors, in decreasing order of importance were informative for predicting depression after stroke: age, education level, BMI, race, smoking, female sex, marital status, history of cancer, and history of MI. The model predicted co-morbid depression among stroke survivors with 70% specificity and 64% sensitivity (overall accuracy 69%).

CONCLUSIONS:
In this nationally representative sample, 10 key factors predicted depression after stroke. Knowledge of these socio-demographic and medical factors could be used to highlight US population subsets which may benefit from more focused depression screening and intervention to enhance stroke outcomes.
Abstract TP184: Half of All Patients With or WIthout a History of Treatment for Hypertension Fail a Blood Pressure Screening: An innovative Urban Eye Clinic Experience
Authors: Dul Mitchell , Nachman Sharon , Arnedo Vanessa , Balucani Clotilde , Burton Dee , Pandey Abhishek , El Zammar Ziad , Borer Jeffrey , Supino Phyllis , Levine Steven R
Published: March 2022

Background:
Innovative strategies are needed to improve blood pressure (BP) surveillance and treatment given the generally poor control in minority communities. People may be more likely to have yearly eye exams than have an annual physical.

Objective:
To assess the effectiveness of co-located screening services for hypertension in an urban, university-based optometry clinic.

Methods:
After IRB approval and informed consent, BPs were taken [Omron (Healthcare Kyoto, Japan) 10 Series automated monitor] on the right arm with the subjects in a seated position. Two measurements were taken 10 min apart prior to pharmacologic dilation of pupils. A brief screening history included current BP medications, presence of medical insurance, and a medical provider. Subjects whose BP was greater than a threshold of 140 systolic/85 diastolic on either of the 2 measurements were instructed to consult with their primary care provider. Patients reporting no known provider were referred for care.

Results:
138 patients were enrolled: 57% female, aged 21 to 86 yrs (mean 57.7 ± 16.27); 61% Black, 21% Caucasian, 12% Hispanic, 6% other; 91% had medical insurance and 48% were currently treated for hypertension. BP measurements > 140/85 were found in 50% (69/138). Of these 69 subjects, 41 (63%) were female. Of the uninsured, 5 of 13 (38%) exceeded the BP threshold. Among subjects currently treated for high BP, 50% exceeded the threshold. This group had a mean systolic BP = 158 (SD 6), median = 152 and a diastolic mean = 94 (SD 8), median = 92. Patients with no prior history of high BP had a mean systolic = 154 (SD 14), median =152, and a diastolic mean & median = 93 (SD 6) and they were > 2x as likely to have a reading of > 85 mmHg diastolic (n=21) vs. >140 mmHg systolic (n=54). Systolic BP showed a weak (r
2
= 0.12) correlation with age; diastolic BP showed no correlation (r
2
= 0.008).

Conclusions:
Co-location of screening services was accepted by the patients served by this urban, academic optometry clinic. Despite being under treatment for hypertension, half the group continued to have measurements associated with at least a doubling of the risk of stroke. Our data suggest that identification of urban, minority patients at risk for stroke could be readily identified by non-traditional health care providers.
Abstract TP204: Frequency Of Coronary Artery Stenosis Greater Than 75% In Patients With Carotid Artery Stenosis Treated With Cas: Evaluation Using Coronaty Cta And Coronary Angiography
Authors: Tanaka Yuko , Tomura Nagatsuki , Kono Kenichi , Yoshimura Ryo , Okada Hideo , Shintani Aki , Terada Tomoaki
Published: March 2022

Background and Purpose:
Acute myocardial infarction(AMI) occurs in 1-2% of patients treated with carotid artery stenting(CAS), and is considered as one of the most serious perioperative complication. We assessed coronary artery stenosis in patients treated with CAS using coronary CTA or coronary angiography.

Methods:
Consecutive sixty-two patients (47 men, mean age 73.4 years) treated with CAS were examined by coronary CTA or angiography within 3 months before CAS between January 2010 and August 2012. In patients suspected coronary artery stenosis by coronary CTA, coronary angiography was performed. Significantly coronary artery stenosis was defined as that greater than 75%.

Results:
CAS was performed in 62 patients, and coronary artery was evaluated in 57 patients. Patients with allergic reaction for contrast agents, renal failure, and poor general condition were excluded from this study. Thirty-eight patients had significant coronary artery stenosis. Twenty-nine of them had any history of chest pain, and sixteen patients demonstrated normal ECG. Nine patients had PCI or CABG before admission and twenty-five patients were treated with PCI of CABG at the perioperative period of CAS. No patients had AMI at this period. Any characteristic changes were not found on carotid angiogram and coronary angiogram. However, patients with significant coronary artery stenosis were tend to have peripheral arterial disease (P=0.065) or intracranial artery stenosis (P=0.08) compared with those without coronary stenosis.

Conclusions:
1. The rate of associated coronary artery stenosis in patients treated with CAS is much higher than that previously reported. 2. 70% patients had significant coronary artery stenosis and 40% needed treatment for coronary artery stenosis in our series. 3. Evaluation of coronary artery using CT angiography is effective to identify patients with high risk of AMI at the perioperative period of CAS.
Abstract TP218: Use Of A Tablet Device application (iNeglect) to evaluate Neglect patients
Authors: Chung Seok Jong , Park Eunjeong , Song Tae Jin , Song Dongbeom , Kim Young Dae , Lee Hye Sun , Heo Ji Hoe , Nam Hyo Suk
Published: March 2022

Background:
Patients with unilateral neglect after the right hemispheric lesion fail to respond normally to stimuli on the left side. Several paper-based tests for detecting neglect had been widely used. Here, we developed an application that runs on a tablet device to evaluate unilateral spatial neglect and investigated its feasibility in stroke patients.

Methods:
We enrolled acute ischemic stroke patients with neglect (n = 20) who had at least one of visual, auditory or tactile extinction. By comparison, stroke patients who had cortical lesions without neglect (n = 10), and healthy controls (n = 10) were recruited. The iNeglect application running on the iPad device was developed. In the table setting test of the iNeglect, the subjects were requested to drag the 12 food items on the table, and the deviation of each item from the midline was measured automatically. Line bisection tests using paper or iPad were also performed and compared.

Results:
Among neglect patients, mean deviation to the right side were 2.03 ± 2.11 mm of line bisection on paper, 18.47 ± 20.89 mm of line bisection on iPad, and 15.79 ± 18.17 mm of the table setting test. Patients with neglect showed larger deviation to the right side; in line bisection on paper (compared without neglect, p = 0.016 and control, p <0.001), line bisection on iPad (compared without neglect, p = 0.053 and control, p = 0.009), and table setting test (0.80 ± 7.38 mm of without neglect, p = 0.004 and -2.93 ± 6.78 mm of healthy control, p = 0.001). Results of table setting test was well correlated with that of line bisection tests on paper (r = 0.487, p<0.001) and iPad (r = 0.511, p<0.001).

Conclusions:
The iNeglect application was feasible in discriminating the patients with neglect and recognizing the right side deviation. The iNeglect application might be helpful to evaluate neglect patients and to objectify neurological deficit.
Abstract TP219: Implantation With Reveal XT After Cryptogenic Stroke Is A Useful Tool To Detect Previously Undiagnosed Atrial Fibrillation
Authors: Holtzman Matthew C , Foster Nathan , Shah Depak
Published: March 2022

Cryptogenic strokes are those ischemic cerebral events with no clear etiology, many of which have embolic characteristics. It is hypothesized that many of these emboli are due to undiagnosed and asymptomatic atrial fibrillation (AF).
1
Our study selected patients with cryptogenic strokes for implantation with the Reveal XT insertable cardiac monitor with the hope of detecting AF in these patients.

Methods:
Patients with ischemic strokes had MRI or CT performed to visualize the infarct. A neurologist determined as to whether the infarct was lacunar, and due to small vessel disease, or if it was an embolic appearing stroke based on the infarct’s size and location (cortical, wedge shaped infarct, multiple vascular territories, watershed territory). If the infarct appeared embolic, and the patient had no history of AF, a full stroke workup was initiated consisting of fasting lipid panel, bilateral carotid dopplers, MRA or CTA of the head, Transesophageal Echocardiogram (TEE), continuous telemetry and hypercoagualable labs if age of the patient was <50). If the stroke was in the posterior circulation, a CTA or MRA of the neck replaced the bilateral carotid dopplers. Patients who had an embolic appearing stroke with a negative TEE, no episodes of AF on cardiac telemetry, MRA or CTA negative for a focal area of stenosis, and carotid Doppler examinations showing less than 50% ipsilateral stenosis were diagnosed as having a cryptogenic stroke. These patients were then offered implantation with the Reveal XT with follow up by a cardiac electrophysiologist who would adjudicate any triggered episodes of atrial fibrillation.

Results:
Following this protocol, 22 patients were successfully implanted with the Reveal XT device. Of these patients, 9 were discovered to have AF, or 41% yield. Once diagnosed with atrial fibrillation, these patients were then placed on appropriate anticoagulation therapy.

Conclusion:
Based on the above results, the Reveal XT insertable cardiac monitor is useful in detecting AF in patients with embolic appearing cryptogenic strokes with otherwise negative workup, and can ultimately change the patient’s therapeutic regimen. Footnotes
1
Finsterer J, (June, 2010) “Management of Cryptogenic Stroke”
Acta Neurol Belg
. 110(2):135–47.
Abstract TP226: Association Of Alpha2-macroglobulin As A Novel Biomarker With Acute Ischemic Stroke
Authors: Nezu Tomohisa , Hosomi Naohisa , Aoki Shiro , Ohtsuki Toshiho , Yamawaki Takemori , Matsumoto Masayasu
Published: March 2022

Background:
We have identified alpha2-macroglobulin as an acute stroke biomarker by using proteomic technologies with two-dimensional gel electrophoresis (2D-PAGE) and liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). Alpha2-macroglobulin is known as a protease inhibitor, which enhance procoagulant properties by the neutralization of plasmin, plasminogen activators and metalloproteinases. The objective of this study was to evaluate the usefulness of serum alpha2-macroglobulin levels in acute ischemic stroke patients.

Methods:
Patients with acute ischemic stroke (n=159; 93 male and 66 female, 71.6±10.3 years) and patients with no previous stroke (n=77; 38 male and 39 female, 70.7±9.5 years) were consecutively enrolled in this study. Stroke subtype was evaluated based on the TOAST classification. Serum alpha2-macroglobulin levels were measured by nephelometry.

Results:
Serum alpha2-macroglobulin levels at admission in patients with acute ischemic stroke was higher than that in control patients (230.2±5.4 vs. 205.0±7.8 mg/dl, P=0.009). Higher age and white matter lesions by using Fazekas classification were significantly associated with high serum alpha2-macroglobulin levels (P=0.001 and P=0.005). After multivariate logistic regression analysis with sex, age, hypertension, diabetes mellitus, dyslipidemia, and atrial fibrillation, the highest quartile of serum alpha2-macroglobulin levels was independently associated with acute ischemic stroke (OR 1.52, 95% CI 1.13-2.08, P=0.005).

Conclusion:
Alpha2-macroglobulin, which was identified by using proteomics, was associated with higher age and white matter lesions. Additionally, serum alpha2-macroglobulin levels was associated with acute ischemic stroke independently from the other factors. Increased alpha2-macroglobulin may be involved in pathophysiology of acute ischemic stroke.
Abstract TP230: Left Atrial Appendage Volume Is Increased In More Than Half Of Patients With Cryptogenic Stroke
Authors: Taina Mikko , Vanninen Ritva , Hedman Marja , Jäkälä Pekka , Sipola Petri
Published: March 2022

Background:
Ischemic stroke without a well-defined etiology is labelled as cryptogenic, and it accounts for 30 − 40 % of strokes in modern stroke registries. Enlarged left atrial appendage (LAA) is the most typical origin for intracardiac thrombus formation. We studied whether increased LAA volume detected with cardiac computed tomography (cCT) constitutes a risk factor in cryptogenic stroke patients.

Materials and methods:
Consecutive stroke or TIA patients with cryptogenic etiology for stroke after profound clinical, radiological and cardiological investigations were selected for the study. The 1993 TOAST criteriae modified by 2010 EAE recommendations for defining cardiac sources of embolism were used for classification. Eighty-two patients (57 males; mean age 58 years) were identified. Forty control subjects without cardiovascular diseases, matched for age and gender, were selected for pair-wise comparisons (21 males; mean age 54 years). LAA volume adjusted for body surface area was measured three dimensionally by tracing the borders of LAA on CT slices. The upper limit for normal LAA volume was defined as mean + 2 SD in control subjects.

Results:
In control subjects LAA volume was 3.4 ± 1.1 mL/m
2
(range 1.3 − 6.0 mL/m
2
). The upper limit for normal LAA was 5.6 mL/m
2
. Of the patients with cryptogenic stroke/TIA 45 (55 %) had enlarged LAA. In matched pair-wise comparisons LAA volume was 67 % larger in cryptogenic stroke/TIA patients than in control subjects (5.7 ± 2.0 mL/m
2
vs. 3.4 ± 1.1 mL/m
2
;
P
< 0.001).

Conclusions:
LAA is significantly enlarged in more than half of patients with cryptogenic stroke, and thus do not have atrial fibrillation as a preceding risk factor. LAA thrombosis may contribute in the pathogenesis of stroke in patients considered to have cryptogenic stroke after conventional evaluation.
Abstract TP233: Comprehensive Stroke Center Optimization in the United States
Authors: Carr Brendan G , Wolff Catherine S , Mullen Michael T , Kasner Scott T , Dailey Karl A , Albright Karen C , Branas Charles C
Published: March 2022

Background:
Stroke is a time critical disease. Regionalized systems of care are necessary to ensure that patients can be rapidly transported to hospitals with the necessary resources to provide high quality care. The introduction of comprehensive stroke center (CSC) certification presents a unique opportunity to use systems science to guide the development of population-based stroke care for the US. We aim to describe the impact of optimally placed CSCs on access to stroke care nationwide.

Methods:
We defined access as the percentage of people per state who could reach a CSC in 60 minutes or less by ground EMS transport, calculated using road network distances, posted speeds and empirically-derived prehospital care intervals. Hospitals certified as Joint Commission primary stroke centers (PSC) by 12/31/2010 were considered candidate sites. A greedy adding algorithm, in which CSCs were sequentially added to the system while building upon the previously prescribed system, was used to sequentially determine the best locations for up to 20 CSCs per state.

Results:
The average state reached a maximum of 53.3% (IQR 35.0-71.6%) access with a mean marginal increase of 31.0% (IQR 16.2-40.8%) for the 1
st
, 8.8% (IQR 5.1-13.1%) for the 2
nd
, and 4.2% (IQR 0.0-6.8%) for the 3
rd
CSC addition (partial results shown in Figure).

Conclusions:
Operations research techniques can inform the design of efficient stroke care systems by determining optimal locations for CSCs. However, existing candidate sites are clustered and ground transport alone leaves much of the population without access. Collaborative approaches including prehospital helicopter transport and inter-facility transfers need to be developed to ensure access to high quality care for all Americans.
Abstract TP243: IMPACT:
I
nfluence of
M
ultiple
P
rocess of care
A
ssessment times on
C
erebral ischemia
T
reatment and outcomes
Authors: Guzik Amy K , Raman Rema , Ernstrom Karin , Rapp Karen , Meyer Dawn M , Hemmen Thomas , Meyer Brett C
Published: March 2022

Background:
Get With the Guidelines (GWTG) emphasizes a focus on process of care times in the acute stroke evaluation to optimize door to needle time. We looked at acute process of care time points to evaluate individual impact on time to treatment and 90 day outcome.

Methods:
The UCSD SPOTRIAS prospectively collected database was analyzed for patients seen in acute stroke code, excluding inpatient codes. Multivariable regression models using an independent variable of 90 day mRS were used. Groups were defined as ≤/ > GWTG time points: arrival to stroke code 10 minutes, arrival to neurologic exam 15 minutes, arrival to imaging 25 minutes, and arrival to lab results 45 minutes. Models were adjusted for pre-specified covariates: pre-stroke mRS, age, gender, smoking, baseline NIHSS and glucose, and IV tPA.

Results:
We analyzed 2903 patients- 481 treated with IV tPA, and 1023 with 90 day outcomes. All timeline goals led to significantly shorter arrival to decision times (all p<0.0001). These timepoints were also associated with decreased arrival to treatment time in IV tPA treated patients (all p<0.0001). However, after adjusting for baseline characteristics, no significant difference in 90 day mRS was observed in any comparison. Good outcome was more frequent with time to treatment ≤ 60 minutes (50.91% vs 41.76%, p=0.0522).

Conclusions:
Time to decision and treatment were significantly shorter when the Get With the Guidelines timeline was followed. This reinforces that each aspect of the acute stroke evaluation must be efficient to expedite time to treatment. No difference was seen in 90 day outcome despite an expedited acute evaluation, emphasizing the importance of symptom onset to treatment time, and especially onset to arrival time, as integral to patient outcome. Further analyses focusing solely on the acute ischemic stroke subset, particularly those arriving within the tPA treatment window, are ongoing.
Abstract TP248: Vascular Neurologists Increase the Frequency of Intravenous Thrombolytic Administration
Authors: Grysiewicz Rebbeca , Garoza Jonathan , Chan Shu B , Khaja Aslam M , Hoelzel Sandra , Shafi Neelofer , Testai Fernando , Gordon Jeffrey , Ruland Sean
Published: March 2022

Background:
It is estimated that only 1-3% of ischemic stroke patients receive IV r-tPA. There are multiple reported barriers that impede the administration of IV-tPA in ischemic stroke patients. However, one specific barrier continually cited by emergency room physicians is a lack of neurological support. In addition, many general neurologists do not regularly treat stroke patients, and therefore do not feel comfortable administering IV r-tPA. We sought to determine if 24/7 availability of vascular neurologists either at the bedside or via telemedicine would increased the frequency IV r-tPA administration in a local community hospital compared to general neurologists via phone consultation.

Methods:
We reviewed the stroke database and determined how many patients presenting with an acute ischemic stroke received IV r-tPA within 4.5 hours during the 14 months before and the 14 months after the implementation of 24/7 vascular neurology availability. We also collected patient age, time of onset, time of arrival, and NIH stroke scale. The student’s t-test or Fisher’s exact test was used to calculate p values for significance when appropriate.

Results:
Between January 1, 2010 and March 22, 2011, 408 stroke emergencies were activated and 7 patients received IV r-tPA under the consultation of general neurologists. Between March 23, 2011 and May 27, 2012, 291 stroke emergencies were activated and 39 patients received IV r-tPA under the consultation of vascular neurologists (1.7% vs. 13.4%, p<0.0001). The mean NIHSS for patients that received IV r-tPA before the 24/7 vascular neurology availability was 11.80, and the mean NIHSS for patients that received IV r-tPA after the 24/7 vascular neurology availability was 13.86 (p=0.61). In 2012, a change in the time window criteria of when to activate an acute stroke emergency decreased the number of stroke emergencies recorded in the second half of the database.

Conclusion:
The 24/7 availability of vascular neurologists increased the IV r-tPA administration rate by more than 5 fold. Access to stroke expertise significantly improves the number of ischemic stroke patients that receive IV r-tPA within 4.5 hours.
Abstract TP253: Adjuvant Treatment with N-acetyl-seryl-aspartyl-lysyl-proline Extends the Therapeutic Window of Tissue Plasminogen Activator in a Rat Model of Embolic Stroke
Authors: Zhang Li , Chopp Michael , Zhang Zheng Gang
Published: March 2022

N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP) is a peptide normally found in human plasma, which has been shown to exert anti-inflammatory and pro-angiogenic activities in the experimental cardiovascular diseases. The present study evaluated the neuroprotective effect of AcSDKP alone and in combination with delayed thrombolytic therapy on focal cerebral ischemia. Rats subjected to embolic middle cerebral artery occlusion were treated with: 1) AcSDKP (2.4mg/kg for 3 days) starting at 1 (n=6), or 4h (n=5) after stroke; 2) combination treatment of tissue plasminogen activator (tPA, 10mg/kg) and AcSDKP (n=12) starting at 4h after stroke; 3) tPA at 4 h after stroke (n=10); 4) saline (n=10). Plasma and cerebrospinal fluid (CSF) samples were taken 24h post stroke to assess the AcSDKP activity by EIA assay. Infarct volume and the incidence of hemorrhage were measured at 7 days after stroke. Monotherapy with AcSDKP starting 1h after stroke onset significantly (p<0.05) reduced lesion volume (20±4% vs 37±4%) and neurological deficits compared with saline treated rats. In addition, while monotherapy with AcSDKP or tPA at 4h failed to reduce lesion volume (34±8% and 38±1%, respectively), combination treatment with tPA and AcSDKP starting 4h after stroke onset significantly reduced volume (15±2%) and exhibited a robust improvement in neurological outcome compared with monotherapy of AcSDKP or tPA. Combination of AcSDKP and tPA did not increase brain hemorrhage measured 7 days after stroke. Concurrently, the combination treatment significantly reduced the density of transforming growth factor β (TGFβ) positive vessels (30±3/mm
2
) compared with monotherapy of tPA (54±5/mm
2
) or saline (47±4/mm
2
), and completely blocked tPA-induced increase in the density of nuclear transcription factor-κB (NF-κB) positive vessels (9±1/mm
2
vs 13±2/mm
2
in tPA monotherapy group). Treatment with AcSDKP significantly increased AcSDKP levels in plasma (9±3nM vs 3±1nM in control) and CSF (6±2nM vs 3±1nM in control). Our data indicate that: 1) AcSDKP passes the BBB and reduces ischemic cell damage, 2) Combination treatment with AcSDKP and tPA extends the therapeutic window for thrombolysis, and 3) NF-κB and TGFβ signaling are likely involved in the neuroprotective effect of AcSDKP.
Abstract TP256: Targets of Vascular Protection in Acute Ischemic Stroke Differ in Type 2 Diabetes
Authors: Cobbs Aisha , Li Weiguo , Prakash Roshini , Pillai Bindu , Ogbi Safia N , Coucha Maha , Johnson Maribeth , Fagan Susan , Ergul Adviye
Published: March 2022

Background:
Hemorrhagic transformation (HT) is an important complication of acute ischemic stroke particularly in diabetic patients receiving thrombolytic treatment with tissue plasminogen activator (tPA), the only approved drug for the treatment of AIS. The objective of the current study was to determine the effects of acute inhibition of the mediators of HT (i.e., NFkB, peroxynitrite, and matrix metalloproteinases) on vascular injury and functional outcome in a diabetic model of cerebral ischemia.

Methods:
Ischemia was induced by middle cerebral artery occlusion in control and type 2 diabetic Goto-Kakizaki rats. Treatment groups received a single dose of peroxynitrite decomposition catalyst FeTPPs, non-specific NFkB inhibitor curcumin, or broad-spectrum matrix metalloproteinase (MMP) inhibitor minocycline at reperfusion. Post-stroke infarct volume, edema, hemorrhage, neurological deficits, and MMP-9 activity were evaluated.

Results:
All therapies reduced MMP-9 and HT in diabetic groups. In addition, acute curcumin and minocycline therapy reduced edema in these animals. Improved neurological function was observed in varying degrees with treatment as indicated by beam-walk performance, modified Bederson scores and grip strength; however, infarct size was similar to untreated diabetic animals. In control animals, all treatments reduced MMP-9 activity yet bleeding was not improved. Neuroprotection was only conferred by curcumin and minocycline.

Conclusion:
Uncovering underlying mechanisms contributing to the success of acute therapy in diabetes will advance tailored stroke therapies.
Table 1
. Summary of experimental stroke data. SE are shown in parentheses.
a
p<0.05 vs. untreated control,
b
p<0.05 vs. untreated,
c
p<0.05 vs. untreated diabetes,
d
p<0.001 vs. untreated control,
e
p<0.01 vs. untreated control,
*
All values in this data set were below detection.
Abstract TP257: Endothelial Cell and Smooth Muscle Cell Specific Tsc1 Deficiency are Important Mediators of Ischemic Stroke
Authors: Ahn Yong-Joo , Kim Hyung-Hwan
Published: March 2022

Background and Purpose:
To determine the function of Tsc1 in endothelial cells (Tie2CreTsc1
flox/+
) and vascular smooth muscle cells (SM22CreTsc1
flox/flox
) in transient focal cerebral ischemia, we hypothesized that Tsc1 deficiency in endothelial cells and smooth muscle cells may play an important role in ischemic stroke
via
mTOR/S6 signaling pathways.

Methods:
To determine the effect of endothelial cell and smooth muscle cell specific Tsc1 deficiency in transient focal cerebral ischemia, we generated Tie2CreTsc1
flox/+
and SM22CreTsc1
flox/flox
mice. Crossing floxed Tsc1 with Tie2Cre and SM22Cre transgene mice expressing Cre recombinase in endothelial cells (ECs) and smooth muscle cells (SMCs) resulted in mice in which vascular SMC mRNA expression was reduced by approximately 70~80%. Isoflurane-anesthetized Tie2Cre, SM22Cre, Tie2CreTsc1
flox/+
, SM22CreTsc1
flox/+
and SM22CreTsc1
flox/flox
mice (20-22g) underwent 2h focal cerebral ischemia (Middle Cerebral Artery Occlusion; MCAO) induced with a 8.0 nylon monofilament coated with a silicone resin/hardener mixture introduced into the left internal carotid artery up to the anterior cerebral artery.

Results:
Compared to control (Tie2Cre and SM22Cre) mice, Tie2CreTsc1
flox/+
, SM22CreTsc1
flox/+
, and SM22CreTsc1
flox/flox
mice decreased cerebral infarct size (45.5 ± 11.8 mm
3
(
p
<0.001), 51.0 ± 6.1 mm
3
(
p
<0.001) and 31.8 ± 11.9 mm
3
(
p
<0.001)
vs.
92.6 ± 6.1 mm
3
, n=5-10) and improved neurological deficit score (2.0 ± 0.5, 2.4 ± 0.3 and 1.6 ± 0.2 (
p
<0.01)
vs.
3.0 ± 0.2, n=5-10) versus control mice. Infarction volume was reduced
via
activation of mTOR and S6, a downstream target of mTORC1 in both endothelial cell and smooth muscle cell specific Tsc1 deficient mice.

Conclusion:
These results suggest that endothelial cell and smooth cell specific Tsc1 deficiency are important mediators of ischemic stroke
via
mTOR signaling pathways.
Abstract TP258: Oleic Acid Decreased Brain Infarct Volume In Middle Cerebral Artery Occlusion Rats By Peroxisome Proliferator-Activated Receptor γ Activation
Authors: Lee DongHwan , Lee Hoyeon , Lee Donghun , Choi Jingyu , Song Jungbin , Gaire Bhakta , Kim Hocheol
Published: March 2022

OA, a monounsaturated ω-9 fatty acid, is most abundant in all dietary fats and oils, especially olive oil, canola oil and high-oleic sunflower and safflower oil. OA was reported to have an anti-inflammatory effect by inhibiting reactive oxygen species (ROS), p38 MAPK, and Akt/IKK/NF-κB signaling pathways in LPS-stimulated BV2 microglia. The accumulation of FFAs after cerebral ischemia has been thought to contribute to injury-associated secondary brain damage by direct and indirect mechanisms. However, the role of OA has not been paid attention or known for exacerbating neuronal cell death in ischemic conditions.

We hypothesized that OA may exert important role on the neuroprotective effect in ischemic rat brain and this effect exert through PPARγ activation. The infarct volume of systemic administration of OA in transient middle cerebral artery occlusion (MCAo) rat was measured after pretreatment of the PPARγ antagonist, GW9662 in order to determine whether PPARγ activation is critical for this effect, and the effect was compared with non-treated group. The expression of COX-2 and MMP-9 was investigated and the induction of HO-1 was also investigated by immunohistochemistry, RT-PCR and zymography in order to confirm the mechanism via activation of PPARγ.

OA decreased infarct size induced by MCAo as late as 3 h after the injury, and the effect of OA was inhibited by the pretreatment of GW9662, a PPARγ antagonist. OA also inhibited the COX-2 and MMP-9 expression and induced HO-1 gene in MCAo rats.

In conclusion, OA significantly reduces the infarct volume of MCAo rats through anti-inflammatory and anti-oxidative effect by acting, at least partly, as a PPARγ agonist. Given that this compound was administered as late as 3 h after the onset of the ischemic damage, OA might be very useful for stroke therapy.
Abstract TP262: Pulsed Electromagnetic Field (PEMF) Increases Microvascular Flow And Tissue Oxygenation In the Normal Rat Brain
Authors: Bragin Denis E , Statom Gloria , Nemoto Edwin M
Published: March 2022

Introduction:
Pulsed Electromagnetic Field (PEMF) treatment has been shown to improve wound healing through increased nitric oxide levels. Thus, we hypothesized that PEMF improves microvascular (MV) flow and tissue oxygenation in the brain.

Methods:
Using in-vivo 2-photon laser scanning microscopy (2PLSM) over the parietal cortex of the normal rat brain, we measured MV red blood cell (RBC) flow velocity, diameters (range 3 to 15 μm which includes arterioles and venules), and tissue oxygenation (NADH fluorescence) before, during 30 minutes PEMF treatment and for three hours thereafter (three sessions with 30 min intervals). Doppler flux (0.9 mm probe diameter), arterial blood pressure, intracranial pressure, and arterial blood gases were concurrently monitored.

Results:
Microvascular flow velocities and diameters increased after PEMF treatment. Average MV diameters (300 MV measured in each of six rats) increased from 9.1±1.8 μm before to 9.4±2.1 μm during PEMF treatment (n=6, p<0.05). Blood flow velocities also increased by 4.4±1.3 and 2.3±1.1 % during and after PEMF treatment respectively in comparison to baseline (p<0.05). PEMF treatment decreased NADH autofluorescence indicating better tissue oxygenation and increased blood supply (96.1±2.4 and 98.2±1.3 % during and after PEMF treatment, respectively, compared to the baseline, p<0.05). Laser Doppler flux averaged over a brain volume of 1 mm3 was unchanged before and during PEMF treatment.

Conclusions:
Thirty minutes of PEMF treatment induced MV dilation, increased RBC velocity and tissue oxygenation that persisted for 3 hours. Within the 3-hour period, however, MV diameters and RBC velocities gradually returned to baseline. Whether the effects observed are nitric oxide induced remains to be determined.
Abstract TP263: The Effect Of Moderate And Excessive Alcohol Exposure On Male Experimental Stroke Outcomes In Mice Is Androgen-Independent
Authors: Chen Yingxin , Zhang Ling , Libal Nicole L , Murphy Stephanie J
Published: March 2022

Heavy alcohol use is a major stroke risk factor while moderate alcohol use may offer protective benefits. We have shown that moderate ethanol (EtOH) exposure reduces while excessive EtOH exposure increases cortical infarct volume after experimental stroke in male and female mice. The effect of either moderate or excessive EtOH exposure levels in cortex is lost in ovariectomized mice, indicating female sex steroids may be involved in the female response to EtOH exposure and experimental stroke. However, it is unknown if male sex steroids (androgens) might alter the effect of varying EtOH exposure levels on male stroke outcomes. We determined the role of androgens in the male response to EtOH exposure and experimental stroke. Male mice were castrated (CAST) 7-8 days before EtOH exposure and middle cerebral artery occlusion (MCAO) to reduce endogenous androgens. Intact and CAST males were given 0.25 g/kg (moderate dose, n=11) or 2.5 g/kg (excessive dose, n=11) EtOH IP 1 h before 45 min of MCAO. These doses mimic moderate (1-2 drinks daily) or excessive (>4 drinks daily) alcohol use in men based on blood EtOH concentrations. Control male (n=11) and CAST mice (n=10) were given saline (0.015 mL/g) IP 1 h before MCAO. Infarct volume (% contralateral structure) was determined at 72 h reperfusion by analysis of coronal brain slices stained with 2,3,5-triphenyltetrazolium chloride. In contrast to saline treated mice (EtOH vs. saline), acute moderate EtOH exposure reduced (p<0.05) cortical infarct volume in intact (41+3% vs. 54+1%) and CAST (23+5% vs. 34+5%) males. Following acute excessive EtOH exposure, cortical infarct volume was increased (p<0.05) in male (62+2% vs. 54+1%) and CAST (47+4% vs. 34+5%) mice compared to saline treated mice. Clinically, our findings suggest that moderate alcohol use may positively while excessive alcohol use may negatively alter stroke outcomes in men regardless of androgen status. Future studies will need to address the role of androgens in aging male brain as gradual androgen loss during aging (andropause) may not have similar effects on the male brain’s response to EtOH exposure and experimental stroke as an abrupt loss of androgens in CAST mice.
Abstract TP264: Effects of Intra- and Post-Ischemic Normobaric Oxygen Therapy on Long Term Outcomes After Focal Ischemic Stroke
Authors: Esposito Elga , Mandeville Emiri T , Hayakawa Kazuhide , Lo Eng H , Singhal Aneesh B
Published: March 2022

Background:
Several rodent studies have documented neuroprotection with normobaric oxygen (NBO) therapy in acute ischemic stroke. These prior studies have typically utilized transient middle cerebral artery occlusion (MCAO) models with intra-ischemic NBO delivery, and measured outcomes at early time frames (24-48 hours). The effects of intra-ischemic and post-reperfusion NBO on long-term outcomes are not clear.

Methods:
Adult male Sprague-Dawley rats were subjected to right MCAO for 100 minutes and randomly assigned to one of 3 groups in blinded fashion: 30% inspired oxygen (Controls), or 100% oxygen starting 15 minutes after MCAO for either 85 minutes (Intra-ischemic NBO), or 165 minutes (Prolonged NBO, i.e. intra-ischemic plus post-reperfusion hyperoxia). Isofluorane anesthesia was maintained for 180 minutes in all groups. Arterial blood gases, BP and heart rate were monitored periodically. Pathological infarct volumes, body weight, immunohistochemistry (for microglial/astrocyte activation, and angiogenesis), and neurofunctional outcomes (forelimb placement test, body swing test and neuroscore), were quantified after 2 weeks by a blinded investigator.

Results:
At 2 weeks, infarct volumes were significantly reduced with Intra-ischemic NBO (132±92 mm
3
vs. Controls, 257±101 mm
3
, p<0.05), and tended to be reduced with Prolonged NBO (166±99 mm
3
). Intra-ischemic NBO significantly (p<0.05) improved outcomes for weight loss (0±0 grams vs. Controls, 52±55.8 grams), forelimb placement test (2.4±2.3 vs. Controls, 5.3±3.3) and body-swing test (18.6±1.1 vs. Controls, 25.1±4.2), but not neuroscore (1.3±1.2 vs. Controls, 1.4±0.5). These functional outcomes were not significantly different between Controls and the Prolonged NBO group. NBO therapy had no effect on angiogenesis markers. However, Intra-ischemic NBO clearly decreased the expression of Iba1, a marker of activated microglia, and GFAP, a marker of activated astrocytes.

Conclusions:
Intra-ischemic NBO affords long-term neuroprotection. Prolonged NBO does not appear to induce neurotoxicity. These results have clinical implications for using NBO as a stroke neuroprotective strategy.
Abstract TP274: Inactivation of Serpinf2 Saves Lives, Prevents Disability and Hemorrhage in Experimental Thromboembolic Ischemic Stroke
Authors: Houng Aiilyan , Wang Dong , Reed Guy
Published: March 2022

More than 15 million individuals suffer ischemic stroke each year. High levels of serpinf2 (Sf2, a2-plasmin inhibitor, a2-antiplasmin) have been identified as a potential risk factor for human ischemic stroke.

Methods:
We examined the integrated effects of sf2 in a thromboembolic MCA stroke model with translational relevance to human disease. Using a blinded observer, neuronal cell death was quantified by TTC staining; hemorrhage and brain swelling were determined by planimetry. Immunohistochemistry was used to assess apoptosis, matrix metalloproteinase 9 expression and breakdown of the blood brain barrier.

Results:
Increasing the levels of sf2 caused larger infarctions by comparison to control mice (51% larger, p<0.002). Sf2 administration also markedly worsened brain swelling (p<0.05) but it did not cause hemorrhage. Conversely, when mice were given an sf2 inactivator (sf2-i), it markedly reduced stroke infarct size (95%) by comparison to control (p<0.001) and TPA-treated mice (p<0.001). Treatment of mice with an sf2-I also markedly reduced mortality rates by comparison to TPA-treated mice (p<0.0005) or control mice (p<0.004). The survival effect was dose-dependent: lower doses of the sf2-I were less effective than higher doses (p≤ 0.05) but still reduced mortality by comparison to control and TPA (p≤ 0.01). Microscopic examination of the brains of mice surviving the initial stroke period (> 12 hrs.) showed that sf2-i reduced stroke infarct size by comparison to control mice or TPA treated mice (p<0.001). There was less hemorrhage in sf2-i treated mice than occurred in control mice (p<0.001) or than in those receiving TPA (p<0.01). Inactivation of sf2 markedly reduced brain swelling by comparison to controls (p<0.001) and TPA-treated mice (p<0.05). Sf2-i treated mice showed no significant disability in Rotarod behavioral testing when compared to sham mice without strokes.

Conclusions:
Sf2 significantly enhances brain injury in ischemic stroke. Since inactivation of Sf2 prevents disability, hemorrhage and death it may prove to be a safe and effective strategy for treating acute ischemic stroke.
Abstract TP279: Effect of Pre-Treatment with Statins on Ischemic Stroke Severity: Does the Doses Matter?
Authors: Martinez Sanchez Patricia , Fuentes Blanca , Ruiz-Ares Gerardo , Martinez-Martinez Marta , Fernandez-Travieso Jorge , Sanz-Cuesta Borja Enrique , Cuellar-Gamboa Lorena , Diez-Tejedor Exuperio
Published: March 2022

OBJECTIVE:
To examine the effect of pre-treatment with statins, at high (80 mg) and non-high (<80 mg) doses, on ischemic stroke (IS) severity in clinical practice.

METHODS:
prospective study of IS admissions to our Stroke Unit during a 3-year period (2008-2010). Demographic data, vascular risk factors, previous treatments (statins, ACE inhibitors, ARB, antithrombotic drugs), stroke severity (NIHSS), stroke subtype, in-hospital complications, length of stay and functional status at discharge (mRS) were collected. Mild stroke severity was defined as NIHSS <=5 on admission. Good outcome was defined as mRS <= 2 at discharge. Multivariable regression models and matched propensity score analyses were used to quantify the association of statins pretreatment, at high and non-high doses, with a mild stroke severity.

RESULTS:
Of 969 IS patients, 23% were using non-high doses and 4.1% high doses of statins before the stroke event. Statins were associated with lower NIHSS scores on admission (median [IQR], 4 [9] for non-statins patients; 4 [9] for non-high doses of statins and 2 [4] for high doses of statins;
p
=0.010). The frequency of mild stroke on admission was higher in the statin groups (57.9% for non-statins, 63.2% for non-high doses of statins and 77.5% for high doses of statins,
p
=0.026). High doses of statins were related with favourable outcomes at discharge, although this was not statistically significant (66.6% for non-statins group, 64.7% for non-high doses of statins and 75% for high doses of statins,
p
=0.443). After multivariable adjustment, pretreatment with statins was associated with higher odds of mild stroke severity and this effect was greater at high doses (OR=1.637, 95% CI 1.156-2.319 for the non-high doses and OR=3.297, 95% CI 1.480-7.345, for the high doses of statins).

CONCLUSION:
Petreatment with statins is associated with lower stroke severity and this effect could be greater at higher doses.
Abstract TP285: Serum Potassium Levels Influence Ischemic Stroke Outcome
Authors: Moussavi Mohammad , Nizam Aaron , Sodhi Ravjot , Alario Joseph , Dababneh Haitham , Panezai Spozhmy , Kirmani Jawad F
Published: March 2022

Introduction:
In cardiac literature hypokalemia has been shown to be assoicated with poor outcomes. It remains unclear whether specific electrolytes, namely potassium, influence stroke outcomes. Our goal in this retrospective study was to test whether the serum electrolyte level at admission and discharge is related to NIHSS and discharge mRS.

Methods:
We conducted a retrospective analysis of ischemic patients admitted to Neuro-ICU between December 2004 and December 2009 at a community teaching hospital. Patient electrolyte levels were documented at admission and discharge as well as discharge mRS. Patients were then divided into groups based on their admission potassium levels as follows: hypokalemic patients (K+ less than 3.5), normokalemic patients (K+ 3.5-5.0), and hyperkalemic patients (K+ greater than 5) and their means were compared in respect to discharge mRS using SPSS software version 20.

Results:
Of 1350 patients, 543 (mean age = 72.5 +/- 14.2, 56% female) were included. Mean potassium level at admission and discharge were 4.31+/- 0.77 mEq/L and 4.12 +/- 0.50 mEq/L, respectively. There was a significant difference between admission and discharge potassium levels, p <0.001. Hypokalemic patients had a significantly higher mRS score than normokalemic patients, p < .05 at admission (p < 0.05) and at discharge (p < 0.05). Hypokalemic patients had a significantly higher NIHSS than normokalemic patients, p < .05. Hypokalemic patients of age ≥ 65 at admission (p <0.05) and at discharge (p < 0.05) had a significantly higher mRS than normokalemic patients. This effect was not seen in patients < 65 years of age.

Conclusion:
Our study suggests that patients with serum potassium levels below normal levels initially and at discharge have worse outcomes , especially in elderly patients. A larger prospective study is warranted to study the effect of endogenous potassium in long term outcomes of patients with ischemic stroke.
Abstract TP288: Introduction of a 24/7 Acute Care Nurse Practitioner-Based Stroke Code Team Improved Compliance with Time Targets
Authors: Koenig Matthew A , Asai Susan M , Moran Jennifer L , Nakagawa Kazuma , Chang Cherylee W
Published: March 2022

Introduction:
An on-site stroke team improves access to IV tPA and speeds assessment of acute stroke patients. The impact of an acute care nurse practitioner (ACNP)-based team to provide 24/7 on-site stroke coverage was studied at a Primary Stroke Center that previously lacked on-site coverage around-the-clock.

Hypothesis:
We hypothesized that the introduction of 24/7 on-site coverage by an ACNP-based acute stroke team would improve compliance with time targets for rapid assessment of stroke patients.

Methods:
A single Primary Stroke Center in Honolulu, HI prospectively collected data on acute stroke code activations for the Get With the Guidelines - Stroke clinical database over a 33-month period. We retrospectively analyzed data for consecutive periods of 19 months before and 14 months after introduction of a 24/7 on-site acute stroke code team that included an ACNP as first responder. Data included patient characteristics, target times, and tPA utilization.

Results:
During the 19-month period prior to ACNP coverage, 200 acute stroke code activations occurred. The mean age of patients was 67.6 years, 51.5% were male, and the mean initial NIH stroke scale score was 15.3 +/- 5.1. Acute ischemic stroke was diagnosed in 47% of acute stroke code activations and 36.2% of those were treated with IV tPA. During the 14-month period after ACNP coverage began, the number of stroke code activations increased to 276. The mean age of patients was 67.5 years, 44.6% were male, and the mean initial NIH stroke scale score was 12.4 +/- 7.2. Acute ischemic stroke was diagnosed in 53.3% of acute stroke code activations and 33.3% of those were treated with IV tPA. After the intervention, door-to-CT-completion time improved from 45.2 +/- 30.1 to 37.8 +/- 20/8 minutes (p=0.192), door-to-lab-result time improved from 42.2 +/- 11.4 to 34.0 +/- 12.4 minutes (p=0.003), and door-to-needle time improved from 60.8 +/- 30.2 to 55.1 +/- 24.3 minutes (p=0.367). After the intervention, compliance with the 60-minute target door-to-needle time improved from 62.1% to 72.3% (p=0.247).

Conclusions:
Introduction of 24/7 on-site ACNP coverage as first responder for acute stroke code activations resulted in modest improvement of compliance with target times for assessment of acute stroke patients.