bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract P739: Magnetic Resonance Imaging-Based Comparison of Temporal Changes in Brain Microstructure After Microemboli Injection in Control and Diabetic Rats: Relevance to Vascular Cognitive Impairment/Dementia
Authors: Chandran Raghavendar , Nie Xingju , Voltin Joshua , He Lianying , Jamil Sarah , Falangola Maria Fatima , Ergul Adviye , Li Weiguo
Published: March 2021

Diabetes doubles the risk of VCID but underlying reasons remain unclear. We reported that diabetic animals are more prone to microemboli (ME)-mediated tissue damage/demyelination and progressive cognitive decline. The goal of the current study was to determine the temporal and spatial changes in cerebral blood flow (CBF) and brain structure after ME injection using MRI. At 10 weeks after onset of diabetes, control and diabetic rats received cholesterol crystal ME (40-70 μm) injection. MRI scans were performed at baseline, weeks 8 and 12 post-ME. Behavioral tests including novel object recognition (NOR) and Y-maze for cognitive function and gait analysis with CatWalk were conducted at same time points as well as week 16. Diabetic animals had baseline deficits in certain cognitive domains and progressively worsened. ME injection caused infarction in two of the diabetic animals (n=6) but were not detected in controls (n=8). Diffusion Tensor Imaging (DTI) metrics showed lower axial diffusivity (DA) in the cortex of diabetic animals, indicating a degree of axonal damage. Post ME, radial diffusivity (DR) was increased while fractional anisotropy (FA) was decreased in the cortex at week 12. At the dorsal hippocampus, mean (MD), DA and DR were all significantly increased by week 12. These changes may reflect loss of tissue integrity and edema in the cortex and loss of axons and myelin damage in the hippocampus of diabetic animals after ME injection. Diabetic animals also showed a significant increase of CBF at week 8 particularly at the dorsal hippocampus and thalamus, which returned to normal by week 12. These results suggest that ME injury and associated cognitive deficits are greater in diabetes, which also causes cerebrovascular dysfunction, and strategies to improve vascular function can be a preventive and therapeutic strategy for VCID.
Abstract P740: Late Effects of Bilateral Carotid Artery Stenosis in an Aged Mouse Model
Authors: Maniskas Michael E , MacK Alexis , Patrizz Anthony , Li Jun , McCullough Louise D , Urayama Akihiko
Published: March 2021

Bilateral carotid artery stenosis (BCAS) or global hypoperfusion is an experimental model of vascular dementia known to effect cognition. Chronic global hypoperfusion increases astrogliosis within the cortex and hippocampus, leading to reduced cognition. It is unknown if global hypoperfusion leads to respiratory deficits that could contribute to cognitive decline. We hypothesized that chronic global hypoperfusion in cerebral blood flow will lead to brain stem gliosis, respiratory dysfunction and progressive cognitive impairment. Female C57Bl/6 mice aged 18 months underwent BCAS (n=8) or sham (n=8) surgery to investigate changes in respiration (frequency, tidal volume, apneas), cognition (y-maze-spatial working memory and fear conditioning-contextual working memory), and changes in cortical and brain stem astrogliosis. Results demonstrated BCAS mice had decreased respiratory frequency and apneas (p<0.05), decreased cognition in both spatial and contextual working memory (p<0.05), and increased astrogliosis (p<0.01) within the cortex and brain stem. To determine if increased astrogliosis within the cortex and brain stem contributes to changes in respiration and delayed cognitive deficits, we administered a TGF-β inhibitor (Gw788388 Hydrate) through an osmotic pump 7 days post-BCAS or sham surgery and followed the mice for 56 days post-surgery. Results demonstrated a reduction in periodic apneas (p<0.01), cognitive deficits (p<0.05), and amelioration in gliosis (p<0.01) when comparing BCAS and sham mice. In conclusion, this study demonstrated global hypoperfusion leads to disrupted respiratory function, late cognitive deficits, and increased brain stem gliosis, that can be rescued through administration of TGF-β inhibitor. Respiratory instability may contribute to post-stroke cognitive deficits, and could be a therapeutic target to improve outcomes in patients with vascular dementia.
Abstract P747: Gpr68 Play a Protective Role in Ischemic Stroke in Mice
Authors: wang tao , Zhou Guokun , he mingdi , xu yuanyuan , Rusyniak w.g. , XU YAN , JI Yonghua , Simon Roger P , Xiong Zhigang , Zha Xiangming
Published: March 2021

Introduction:
Acidosis is one prevalent phenomenon in ischemic stroke. The literature has shown that protons directly gate acid-sensing ion channels (ASICs) and proton-activated chloride channel, both lead to neuronal injury However, it is unclear whether protons activate metabotropic pathways in brain neurons. There are four proton-sensitive G-protein coupled receptors (GPCRs): GPR4, GPR65, GPR68 and GPR132. It remains unknown whether any of these GPCRs mediate acid-induced signals in brain neurons or whether they contribute to ischemia-induced brain injury.

Methods:
Total RNA from human cortical tissue or mouse brain was isolated using TRIzol and an RNase Kit. Standard RT-PCR was performed to determine the expression of these GPCRs in the brain. An in vitro slice injury model was used for functional screening. To determine the effect of ischemia, WT and knockout male mice were subjected to MCAO. To study brain injury, brains were sectioned coronally at 1 mm intervals and stained by vital dye immersion: (2%) 2,3,5-triphenyltetrazolium hydrochloride (TTC). Locomotor analysis and corner test were used to assess behavior outcome. Adeno-associated virus (AAV) -mediated gene delivery was used to determine the outcome of GPR68 overexpression.

Results:
RT-PCR showed that brain tissue expressed GPR4, -65, and -68. The expression of GPR68 was evident at 30 cycles. In organotypic slices, compared to the WT, deleting GPR4 or GPR65 had no effect while deleting GPR68 significantly increased acidosis-induced neuronal injury. At both 24 hour and 72 hour after 45 minutes MCAO, GPR68 deletion increased brain injury (p=0.0020 for 24hour, p=0.0392 for 72hour, Mann-Whitney U test). WT and GPR68-/- mice did not differ in baseline locomotor activities or corner test. On the third day following MCAO, GPR68-/- exhibited significantly more left rotations (p=0.0287, Mann-Whitney U test) than WT animals. Lastly, mice receiving AAV-GPR68 exhibited an average infarct of 21.97 ± 12.4%, significantly (p = 0.0022, Mann-Whitney U test) smaller than those receiving AAV-GFP (37.2 ± 6.8%).

Conclusion:
These data showed that GPR68 functions as a neuroprotective proton receptor in the brain.
Abstract P77: Acute Stroke Trends and Outcomes During the COVID-19 Pandemic in a Multi-System Hospital System in the Western US
Authors: Ovando Renee , Swearingen Natalie R , Stuchiner Tamela L , Corless Leslie , Moreno Crystal Ann , Zurasky John F , Tarpley Jason W , Raychev Radoslav , Baraban Elizabeth
Published: March 2021

Introduction:
We aimed to evaluate the impact of Covid-19 pandemic on stroke systems of care and outcomes within a large multi-hospital system in the Western US.

Methods:
Retrospective data from 37 hospitals within a large multi-hospital stroke registry was analyzed. All patients with a confirmed discharge diagnosis of stroke or TIA during the pandemic (March and April 2020) were compared to cohorts during the same periods in 2018 and 2019. Analyzed factors included demographics, stroke mechanism, admission NIHSS, reperfusion therapy rates (IV TPA and EVT), reperfusion performance metrics (door-to-CT, door-to-needle, door-to-puncture, door-to-first pass), TICI score, discharge and 90-day mRS, discharge disposition, and length of stay. Analyses were conducted using ANOVA, Kruskal-Wallis, or Person’s Chi-square test, as appropriate, adjusting for multiple comparisons.

Results:
Among the 7,201 analyzed patients, 2,378 (33.0%) were admitted in 2018, 2,613 (36.3%) in 2019 and 2,210 (30.7%) in 2020. Fewer patients were hospitalized with TIA during the pandemic compared to 2018 and 2019 (23.6% vs 36.8% vs 39.6%, p<.001). More patients arrived via EMS (52.2% vs 45.7% vs 45.4 %) and fewer via private car (29.8% vs 37.8% vs 38.7%) (p<.001) during the pandemic. Median door-to-CT (in minutes) (26 vs 35 vs 33, p<.001) time was significantly shorter during the pandemic. Additionally, a greater percentage of patients were treated with EVT during the pandemic (7.5 vs 5.7 vs 5.4, p=.005). Shorter arrival-to-first pass times (in minutes) occurred in 2020 compared to previous years (103 vs 119 vs 115, p=0.091) but this difference did not reach statistical significance. Fewer patients were discharged to a skilled nursing facility during the pandemic (12.7%) compared to 2018 and 2019 (15.1% and 15.2%, p=.012). There were no other significant differences in stroke admission volumes, treatment trends, or outcomes between the pandemic and pre-pandemic periods.

Conclusion:
Fewer walk-in strokes and TIAs were hospitalized during the pandemic while an increased rate of thrombectomy procedures occurred compared to the pre-pandemic era. Despite anticipated delays in acute stroke care, our study demonstrates improvement in key triage and treatment times and similar outcomes.
Abstract P771: Monocyte-Chemoattractant Protein-1 Levels in Human Carotid Atherosclerosis Associate With Hallmarks of Plaque Vulnerability
Authors: Georgakis Marios K , van der Laan Sander W , Asare Yaw , Mekke Joost M , Haitjema Saskia , Schoneveld Arjan , de Kleijn Dominique , de Borst Gert Jan , Pasterkamp Gerard , Dichgans Martin
Published: March 2021

Background:
Monocyte chemoattractant protein-1 (MCP-1) is a chemokine recruiting monocytes to the atherosclerotic plaque. Experimental, genetic, and epidemiological data support a key role of MCP-1 in atherosclerosis. Yet, the translational potential of targeting MCP-1 signaling for lowering vascular risk is limited by the lack of data on plaque MCP-1 activity in human atherosclerosis.

Methods:
We measured MCP-1 levels in human plaque samples from 1,199 patients undergoing carotid endarterectomy from the Athero-Express Biobank. We explored associations of plaque MCP-1 levels with histopathological features of plaque vulnerability, clinical plaque instability (symptomatic vs. asymptomatic plaque), molecular markers of plaque inflammation and remodeling, and with incident vascular events up to three years after plaque removal.

Results:
MCP-1 plaque levels were associated with individual histopathological hallmarks of plaque vulnerability (large lipid core, low collagen, high macrophage burden, low smooth muscle cell burden, intraplaque hemorrhage), as well as with a cumulative vulnerability index (range 0-5, beta: 0.42, 95%CI: 0.30-0.53, p=5.4x10
-13
) independently of age, sex, and conventional vascular risk factors. Furthermore, MCP-1 levels were higher among patients with symptomatic, as compared to asymptomatic plaques (p=0.0001) and were associated with the levels of pro-inflammatory cytokines involved in leukocyte adhesion, as well as with matrix metalloproteinase activity in the plaque. In the follow-up analyses, MCP-1 levels were associated with a higher risk of peri-procedural events (up to 30 days after surgery).

Conclusions:
Our findings highlight a role of MCP-1 in human plaque vulnerability, the leading mechanism underlying vascular events like stroke and myocardial infarction. As such, they suggest that interfering with MCP-1 signaling in patients with established atherosclerosis could lower vascular risk.
Abstract P773: Autotaxin and Lysophosphatidic Acid Impair Blood Brain Barrier and Mitochondria Following Ischemic Stroke
Authors: Bhattarai Susmita , Sharma Sudha , Ara Hosne , Bhuiyan Shenuarin , Miriyala Sumitra , Panchatcharam Manikandan
Published: March 2021

Introduction:
Ischemic stroke is a leading cause of death and a serious cause of long-term disability in the US. r-TPA is the only treatment available for stroke. Only 5% of patients receive it, as others have the risk of intracerebral hemorrhage. Ischemic reperfusion (I/R) following stroke exacerbates the condition and initiates various molecular signals, ultimately interrupting blood-brain barrier BBB so, better therapy is in need. Lysophosphatidic acid (LPA) is a bioactive lipid regulating various essential cellular functions such as migration, proliferation, adhesion. Autotaxin (ATX) produces LPA, which then regulates through its six G-protein coupled receptors.

Methods:
Transient middle cerebral artery occlusion (MCAO) with 90 minutes of ischemia and 24 hours of reperfusion was used as a stroke model in mice. LPA was analyzed in plasma with mass spectrometry and in tissue with immunohistochemistry. AR-2 probe fluorescence measured ATX activity. Seahorse analyzer measured the mitochondrial bioenergetics in brain and mouse brain microvascular endothelial cells (MBMEC). Permeability was studied with Electric Cell Substrate Impedance System.

Results:
ATX was elevated in mRNA level with 1.7 fold increased activity following I/R. LPA showed a significant (P<0.01) increase in the plasma of MCAO mice. LPA in the brain tissue of MCAO mice revealed an increased synthesis of LPA by ATX following I/R injury. Brain mitochondria isolated following I/R injury had significantly (P<0.01) reduced the mitochondrial oxygen consumption rate (OCR). Permeability measured in MBMECs showed LPA treatment increases the permeability. Also, the protein levels of junctional proteins such as βcatenin, Claudin5, VEcadherin, and Zo1 were significantly (P<0.05) decreased with LPA exposure. LPA, as a negative regulator of the BBB, caused permeability through LPA-LPAR1-ROCK dependent pathway. MBMECs show impaired mitochondrial function with decreased OCR and elevated glycolysis towards LPA treatment (P<0.01).

Conclusion:
We have shown that LPA and its regulator enzyme ATX play a significant role in ischemic stroke, increasing BBB permeability, and elevating mitochondrial dysfunction. ATX inhibitors as therapy could improve the condition of stroke patients.
Abstract P777: Statistical Modeling of Proteomic Signaling During Stroke in Patients Undergoing Thrombectomy
Authors: Claypoole Sydney , Frank Jacqueline , Sands Madison , McLouth Christopher J , Roberts Jill , Trout Amanda L , Grupke Stephen , Stowe Ann M , Fraser Justin , Pennypacker Keith
Published: March 2021

Introduction:
The previously published Blood and Clot Thrombectomy Registry and Collaboration (BACTRAC) protocol (clinicaltrials.gov NCT03153683) utilizes mechanical thrombectomy to obtain tissue samples for banking. Peripheral blood proximal to the clot and intracranial blood distal from the clot were isolated. Proteomic and statistical analyses revealed normalized (intracranial-systemic) CCL19 expression was a predictor of infarct volume. Statistical modeling analyses were used determine the CCL19-associated proteomic signaling network occurring during ischemic stroke relating to infarct volume.

Methods:
Arterial intracranial and systemic blood samples underwent analysis for inflammatory proteins using Proximity Extension Assay (PEA) via Olink (Olink Proteomics, Boston, MA). Systemic expression was used as an internal control to normalize expression in the intracranial blood. Bivariate regression was used to examine the relationship between the intracranial normalized CCL19 expression and infarct volume. A backwards stepwise regression was then used to determine a model of predictability of infarct volume by CCL19 and associated inflammatory proteins.

Results:
25 subjects (>18 yrs) with a mean infarct volume of 8,172 ± 82,284 mm
3
and mean infarct time of 513 ± 246 minutes were included in this study. Their median age was 64 (24-91) and 10 (40%) were male. 16 subjects (64%) had hypertension, 15 (60%) had BMI > 25, and 6 (24%) had a previous stroke. The stepwise regression model shows normalized expression of 16 proteins correlated with an increase in infarct volume (p<0.005): CCL20, CXCL1, OSM, CD6, OSMR, TGF-alpha, TRANCE, CXCL10, LIF-R, CCL19, CDCP1, Flt3L, CCL23, CD244, TRAIL, NOTCH1.

Conclusions:
In our model, the expression of these proteins were consistently changed, though the directionality differed. LIF-R, NOTCH1, TRAIL, CD6, CCL23, TGF-alpha, and CCL20 were positively correlated, while the expressions of Flt3L, OSM, OSMR, TRANCE, CD244, CDCP1, CXCL1, CXCL10, and CCL19 were negatively correlated with infarct volume. This model depicts the proteomic signaling occurring during stroke in relationship to infarct volume, which reveals potential biomarkers and therapeutic targets for the early phase of ischemic stroke.
Abstract P781: Ischemic Postconditioning Protects Against Hemorrhagic Transformation Induced by Hyperglycemia in Ischemic Stroke
Authors: Chen Hansen , Cheng Michelle Y , Bliss Tonya , Zhao Heng , Steinberg Gary
Published: March 2021

Background:
Hyperglycemia occurs in over 40% of ischemic stroke patients, which induces hemorrhagic transformation (HT) and worsens stroke outcomes. The management of hyperglycemia with insulin did not show favorable outcomes. Thus, strategies for managing hyperglycemia-exacerbated stroke injury are urgently needed. We previously demonstrated that ischemic postconditioning (IPostC) (repeated transient interruption of cerebral blood flow during reperfusion) can reduce brain infarct size and improve neurological outcomes. In this study, we hypothesized that IPostC can reduce HT in ischemic stroke with acute hyperglycemia.

Method:
Male mice were subjected to middle cerebral artery occlusion (MCAO) for 1 hour, followed by reperfusion to mimic ischemic stroke. Glucose was injected before MCAO to induce hyperglycemia. IPostC was initiated upon reperfusion with 3 cycles of 30-second reperfusion followed by 10 seconds of MCA occlusion. Brain infarct was visualized by TTC staining and quantitated using Image J. Hemorrhagic transformation was evaluated by hemorrhagic scores.

Result:
Acute hyperglycemia significantly increased the brain infarct size (by 25%, p<0.01), brain edema (p<0.001) and hemorrhagic transformation (HT) (average HT scores: 0.75 in MCAO group vs 15.6 in MCAO plus hyperglycemia group, p<0.001), Mice with hyperglycemia also exhibited more severe neurological deficit and higher mortality rate at 24 hours after MCAO. 2) IPostC treatment significantly reduced brain infarct size (p<0.01), brain edema (p<0.05) and attenuated HT (p<0.001). Neurological deficit and mortality rate was reduced with IPostC treatment.

Conclusion:
Our findings suggest that IPostC can counteract the effects of acute hyperglycemia and reduce brain injury, edema and HT after stroke. Grant/Other Support: NIH Grant R01NS064136C
Abstract P783: Alpha
7
-Acetylcholine Receptor Signaling Reduces Neuronal Apoptosis After Subarachnoid Hemorrhage
Authors: Dienel Ari , Veettil Remya A , Matsumura Kanako , Kumar T. Peeyush , Blackburn Spiros , Choi HuiMahn A , McBride Devin W
Published: March 2021

Subarachnoid hemorrhage induces neuronal apoptosis which causes acute and long-term memory deficits. Ourhypothesis is that agonism of α7-acetylcholine receptors attenuates neuronal apoptosis and improves memorydeficits in SAH mice. Mice were randomly assigned into the experimental groups. One cohort was euthanizedone day after SAH to assess neuronal apoptosis and signaling pathways. A second cohort survived for 30 dayspost-SAH to test long-term memory function. Inhibitors and an α7-acetylcholine receptor knockout mouse wereused. Neurobehavioral performance was assessed on days 1-3, 5, 7, and 23-28. All outcomes were performedand all data was analyzed by a blinded investigator. The α7-acetylcholine receptor agonist prevented neuronalapoptosis and improved acute memory deficits caused by SAH via activation of the PI3K/Akt pathway in neurons.Agonism of the α7-acetylcholine receptor was beneficial in both male and female mice, although the protectionin females was significantly better than in male mice. α7-acetylcholine receptor agonism did not provide anybenefit in α7-acetylcholine receptor knockout mice subjected to SAH. Treatment with the α7-acetylcholinereceptor agonist for 3 days after SAH led to improved working memory one month after SAH suggesting thatacutely improving neuronal survival can have long-lasting benefits. The α7-acetylcholine receptor may be atherapeutic target for SAH which can promote neuronal survival acutely after SAH, but also confer long-lastingmemory benefits. The findings of this study support the α7-acetylcholine receptor as a treatment target whichmay attenuate the long-term memory deficits which SAH patients suffer from.
Abstract P785: The B Cell Response to Extracellular Glutamate in the Ischemic Brain
Authors: Torres Vanessa O , Turchan-Cholewo Jadwiga , Kong Xiangmei , Plautz Erik J , Monson Nancy L , Goldberg Mark P , Stowe Ann M
Published: March 2021

Background:
Neuronal networks require significant neurotrophic support for functional plasticity after stroke. We showed that B cells exhibit a cell-specific migration pattern in the post-stroke brain. Post-stroke B cell depletion impedes neurogenesis, increases anxiety, and exacerbates memory deficits in mice; deficits generally mediated by brain regions occurring outside the initial infarct.
We hypothesize that the post-stroke microenvironment can enhance neurotrophic capacities of B cells to promote plasticity.

Methods:
Splenic B cells were isolated from 3-5 mo-old male C57Bl/6J mice. B cell N-methyl-D-aspartate receptor (NMDAR) subunits were identified by confocal microscopy. The acute (8 min) Ca
2+
response to 1uM glutamate (glu) +/- NMDAR antagonists (10uM DAPV (competitive NMDAR inhibitor), 30uM ifenprodil (ifen., GluN2B subunit inhibitor), and 10uM TCN201 (GluN2A subunit inhibitor)) was assessed via flow cytometry in B cells (+/- 5ug/mL LPS). B cell viability and neurotrophin (NT)-related genes were assessed by flow cytometry and qPCR, respectively, in B cells (+/- LPS) treated with glu +/- NMDAR antagonists for 24h. Data were analyzed in Graphpad Prism.

Results:
B cells express functional GluN2A- and GluN2B-containing NMDARs that influx Ca
2+
in response to extracellular glu (*p<0.05). While LPS did not impact NMDAR-dependent Ca
2+
influx in most B cell subsets, Ca
2+
influx was significantly reduced by NMDAR antagonists in LPS-stimulated B cells (Effector B cells (DAPV *p<0.05, ifen **p<0.01), Bregs (DAPV *p<0.05, Ifen *p<0.05), B220
+
antibody-secreting cells (ifen *p<0.05, TCN201 *p<0.05)). Furthermore, a 24h glu treatment increased NT (BDNF: 2.28-fold, IL-10: 27.16-fold), NT receptor (TrkB: 1.33-fold) and NMDAR (GluN2A: 2.01-fold, GluN2B: 1.27-fold) expression in LPS-stimulated B cells (vs. untreated controls).

Conclusions:
Our studies show that B cells respond to glu via NMDARs. Our data suggests that exposure to physiologic levels of glu enhance NMDAR-dependent signaling and upregulate NTs and NT receptors. These results are the first to indicate a glu-induced neurotrophic role for B cells in the ischemic brain. Future studies will determine whether B cell-derived NTs can protect neurons after stroke.
Abstract P790: Landiolol Attenuates Global Cerebral Edema Following Experimental Cardiac Arrest in Mice
Authors: Iwai Tomoyuki , Nakayama Shin
Published: March 2021

Introduction:
Cerebral edema following cardiac arrest and cardiopulmonary resuscitation (CA/CPR) is associated with unfavorable neurologic outcome. The Na
+
-K
+
-2Cl
-
water cotransporter NKCC1 is suspected to be a critical mediator of edema formation after ischemia. It is reported that β1 adrenoreceptor antagonists protect neurons following brain ischemia in rodents. β1 adrenoreceptor antagonists inhibit the Na
+
-K
+
-ATPase, which can inhibit driving force of NKCC1 that theoretically reduces cerebral edema following ischemia-reperfusion injury. In this study, we examined whether landiolol, a selective β1 adrenoreceptor antagonist, attenuates cerebral edema following CA/CPR.

Methods:
Isoflurane-anesthetized adult male mice (C57BL/6J, 25-30g) were randomized into landiolol group or control group. After 7-min CA followed by CPR, landiolol (0.5ml, 830μg/ml) was administered by continuous infusion intravenously for 4 hours. Animals in control group were given normal saline (0.5ml) in the same manner. Twenty-four hours after CA/CPR, the brain was removed to assess brain water content using wet-to-dry method. The primary outcome was measurement of the brain water content. Heart rate and arterial blood pressure were recorded. Measured parameters were analyzed by one-way ANOVA with post hoc Tukey-Kramer test using SPSS® statistics 25. Differences were considered statistically significant at a P value < 0.05.

Results:
Brain water contents was increased in control group mice after CA/CPR (n=10) compared with those in sham operated mice (n=5) (79.5±0.85% vs 78.3±0.14%, P=0.003). Compared with control group, landiolol treatment significantly reduced brain water content in mice subjected to CA/CPR (n=12) (78.9±0.51% vs 79.5±0.85%, P=0.04).

Conclusion:
Landiolol attenuated brain edema following CA/CPR. These results may suggest selective β1-blocker could be alternative treatment for neuroprotection in patients who suffered CA/CPR.
Abstract P797: Sex Specific Plasma Protein Changes During Thrombectomy
Authors: Trout Amanda L , Frank Jacqueline , Maglinger Benton , Roberts Jill , Stowe Ann M , Turchan-Cholewo Jadwiga , Grupke Stephen , Fraser Justin , Pennypacker Keith R
Published: March 2021

Introduction:
Sex differences in stroke have been apparent with premenopausal females having a lower incidence of stroke with better outcomes than postmenopausal females and males. We examined sex-specific outcomes and changes in plasma proteins following emergent large vessel occlusions. The previously published Blood and Clot Thrombectomy Registry and Collaboration (BACTRAC), clinicaltrials.gov NCT03153683, allows for analysis of plasma proteins both systemically and distal to the thrombus.

Methods:
Plasma samples, processed in accordance with the BACTRAC protocol, were sent to Olink to run cardiometabolic and inflammatory panels. Demographics are reported as mean±SEM. Significance determined in Prism with Mann-Whitney, t-test, or pair mixed-effect analysis.

Results:
We evaluated 34 subjects, >18 yrs old (20 females, 14 males) enrolled in BACTRAC. There was no significant difference in age (68.9±2.7, 65.4±4.5 yrs, respectively) or comorbidities (hypertension, diabetes, cholesterolemia). Interestingly, males had a larger (p<0.1) change in Modified Rankin Scale (mRS, premorbid-discharge, 3.4±1.8, 2.2±1.6, respectively) with larger infarcts (86,666±30,889 mm
3
, 36,228±10,943 mm
3
, respectively). This coincided with a lower (p<0.05) CTA collateral scores for males compared to females (0.64±0.67, 1.1±0.13, respectively). 12 proteins were significantly (p<0.1) higher in females, compared to males (5 proteins upregulated in both the systemic and intracranial, 3 systemic specific, and 4 intracranial specific). Males had 15 proteins significantly higher than females (3 proteins upregulated in both the systemic and intracranial, 12 systemic specific, and 0 intracranial specific). The most significant intracranial protein for females is coagulation factor XI (F11) and males is transforming growth factor beta-1 (TGFB1). Analysis of an additional 16 subjects has begun to validate the sex specific proteins.

Conclusions:
Unexpectedly, males have larger infarcts and less independence following large vessel occlusions in BACTRAC. We hypothesize this is due to fewer collaterals which leads to sex specific signaling patterns. Additional analysis of the plasma and subjects in BACTRAC are needed to target sex specific therapeutic.
Abstract P82: The Impact of SARS-COV-2 on Stroke Epidemiology and Care: A Meta-Analysis
Authors: Katsanos Aristeidis H , Palaiodimou Lina , Zand Ramin , Yaghi Shadi , Kamel Hooman , Navi Babak B , Turc Guillaume , Romoli Michele , Sharma Vijay , Mavridis Dimitris , Shahjouei Shima , Catanese Luciana , Shoamanesh Ashkan , Vadikolias Konstantinos , Tsioufis Konstantinos , Lagiou Pagona , Alexandrov Andrei V , Tsiodras Sotirios , Tsivgoulis Georgios
Published: March 2021

Background:
Emerging data indicates an increased risk for cerebrovascular events with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus and highlights the potential impact of coronavirus disease (COVID-19) on the management and outcomes of acute stroke. We conducted a systematic review and meta-analysis to evaluate the aforementioned considerations.

Methods:
We performed a meta-analysis of observational cohort studies reporting on the occurrence and/or outcomes of patients with cerebrovascular events in association with their SARS-CoV-2 infection status. We used a random-effects model. Summary estimates were reported as odds ratios (ORs) and corresponding 95% confidence intervals (95%CI).

Results:
We identified 16 cohort studies including 44,004 patients. Among patients with SARS-CoV-2, 1.3% (95%CI: 0.9-1.8%; I
2
=88%) were hospitalized for cerebrovascular events, 1.2% (95%CI: 0.8-1.5%; I
2
=85%) for ischemic stroke, and 0.2% (95%CI: 0.1-0.4%; I
2
=69%) for hemorrhagic stroke. Compared to non-infected contemporary or historical controls, patients with SARS-CoV-2 infection had increased odds of ischemic stroke (OR=3.58, 95%CI: 1.43-8.92; I
2
=43%) and cryptogenic stroke (OR=3.98, 95%CI: 1.62-9.77; I
2
=0%). Odds for in-hospital mortality were higher among SARS-CoV-2 stroke patients compared to non-infected contemporary or historical stroke patients (OR=5.60, 95%CI: 3.19-9.80; I
2
=45%). SARS-CoV-2 infection status was not associated to the likelihood of receiving intravenous thrombolysis (OR=1.42, 95%CI: 0.65-3.10; I
2
=0%) or endovascular thrombectomy (OR=0.78, 95%CI: 0.35-1.74; I
2
=0%) among hospitalized ischemic stroke patients during the COVID-19 pandemic. Diabetes mellitus was found to be more prevalent among SARS-CoV-2 stroke patients compared to non-infected contemporary or historical controls (OR=1.39, 95%CI: 1.04-1.86; I
2
=0%).

Conclusion:
SARS-CoV-2 appears to be associated with an increased risk of ischemic stroke, particularly the cryptogenic subtype. SARS-CoV-2 infection in stroke substantially increases the mortality risk.
Abstract P832: Stroke Disease-Specific Quality of Life Trajectories After Rehabilitation Discharge and Their Sociodemographic and Clinical Predictors: A Longitudinal, Multicenter Study
Authors: Pucciarelli Gianluca , Simeone Silvio , Brugnera Agostino , Greco Andrea , Petrizzo Antonello , Vellone Ercole , Alvaro Rosaria
Published: March 2021

Introduction:
Research on the trajectory of survivors’ quality of life over time has generally focused on the first six months post-stroke, and results are inconsistent. Indeed, while some studies found an improvement of the stroke survivors’ quality of life from one to six months post-stroke, other studies showed an improvement during inpatient rehabilitation but a worsening at six months after discharge.

Aim:
To investigate the longitudinal growth trajectories of disease-specific quality of life dimensions and their predictors over one year.

Methods:
A multicentric longitudinal design were used for this study. Four hundred and fifteen stroke survivors (mean age 70.6
+
12.2 years; 81% ischemic stroke) were recruited after discharge from rehabilitation hospitals and were followed up every three months for one year. Changes in stroke impact scale dimension scores were evaluated using hierarchical linear models and linear, logarithmic, quadratic, and cubic time slope.

Results:
We observed a significant linear and quadratic increase in most stroke impact scale dimensions from the baseline to 12-month follow-up. The communication dimension was stable over time, while the memory dimension increased only linearly. Higher physical dimensions scores were predicted by lower age, hypercholesterolemia, and better physical functioning at baseline, while higher communication was predicted by lower age, better physical functioning, and a diagnosis of peripheral vascular disease. Better memory was predicted by lower age, married status, better physical functioning, and left-hemisphere stroke. Better participation was predicted by lower age and better physical functioning. No predictors were observed for emotion.

Conclusions:
Disease-specific quality of life significant increase from the baseline to 12-month follow-up, especially in physical dimensions. Lower age, hypercholesterolemia, better physical functioning and diagnosis of peripheral vascular disease seem to be predictors or better quality of life. Through the analyses of predictors, we identified stroke survivors who are more at risk and who need more tailored interventions to improve quality of life.
Abstract P836: Barbershop Mediator-Ship: A Pilot Study of a Grass-Root Community Based Stroke Awareness Campaign
Authors: Ayanbadejo Michael Omoniyi , Stoll Nancy M , Taylor Syntyia , Guterman Lee R
Published: March 2021

Background:
Minorities in the United States have disproportionately higher risk of stroke, early-onset, and more severe strokes than non-Hispanic Whites. Hypertension (HTN) is an independent and modifiable risk factor for stroke. Recent prevalence estimates of HTN in minorities in Niagara Region is not available. Health campaign to barbershops is well-established to be effective for HTN management in black men. This pilot study was conducted to screen for HTN in Barbershops to determine the prevalence of HTN in black men in the Niagara Region.

Methods:
Barbershops were randomly selected by convenience, and patron’s participation (≥18 years) were voluntary. Blood pressure (BP) screening and stroke education campaign were conducted concurrently in partnership with 7 barbershop owners in the Niagara Region from September 13, 2019 to February 10, 2020. Participant’s age, race, gender, and BP using automated BP machine were recorded. BP readings were stratified into 3 groups based on severity: High risk (BP ≥ 140/90mmHg), intermediate risk/caution (BP 120-139/80-89mmHg) and low risk (BP ≤ 120/< 80mmHg). Hypertension was defined as BP ≥ 140/90. Data was stored in Excel and analysis performed with SPSS (Statistical Package for the Social Sciences).

Results:
Of the 57 that participated in this study, approximately 75.4% (n=43) were male; 89.4% (n=51) were Black, 5.3% (n=3) were Hispanic and 5.3% (n=3) were other race/ethnicity. Participants’ ages ranged between 18-71 years with a mean age of 36.4 years (95% CI [32.9, 39.8]). Mean systolic BP was 132.14 mmHg (95% CI [128.00, 136.28]) and mean diastolic BP was 86.35 mmHg (95% CI [81.21, 91.50). Approximately 70.0% of total participants were in the high and intermediate risk group categories, with participants younger patients (i.e. age ≤ 40 years) accounted for 73.0% of the high risk group.

Conclusion:
The prevalence of high blood pressure among minorities in Niagara Region is high and above previous estimates reported in the 2017 ACC/AHA guideline (41% to 55%). Barbershops may provide future opportunities for screening and recruiting subjects for interventions that reduce BP and its risk factors. Further studies should be conducted in larger populations to reduce the uncertainties around the prevalence estimate of HTN
Abstract P837: Use of Structured Data Entry in Electronic Health Records Increases Compliance With Stroke Standards and Decreases Time of Chart Abstraction
Authors: Noah Patty , Hackett Chris , Pope Leslie , Buchinsky Kelly , Tayal Ashis H , Cerejo Russell
Published: March 2021

Introduction:
Comprehensive Stroke Centers (CSC) provide a high level of care and are held to rigorous standards. Meeting these standards can be challenging in a tertiary care center where multiple services admit the stroke patient population. This also hinders the compliance in meeting these standards as well as created a delay in data abstraction due to nonuniform documentation. A Cerebrovascular Navigator (CV Navigator) is a structured data entry form developed within the electronic health records (EHR) platform to document clinically relevant data in an effort to increase compliance with CSTK measures and to decrease the time for abstraction.

Method:
The CV Navigator was developed by a team of physicians, nurses, abstractors and informatics personnel. The team specifically focused on CSC measures as per Joint Commission. The CV Navigator captured data required for abstraction for submission into Get with the Guidelines (GWTG) database. We compared compliance for two years, before (2015-2016) and after (2017-2018) implementation of the CV Navigator at our comprehensive stroke center.

Results:
During the study 5869 (2842 before, 3027 after) acute stroke patients were admitted. Utilizing the CV Navigator simplified data abstraction which decreased GWTG submission from three months to two weeks post discharge. Compliance for documenting severity measurement (CSTK-3) significantly increased from 66.7% before (n=375/562) to 87.6% after implementation of CV Navigator (n=496/566), OR =3.53 (95%CI 2.60 - 4.80), p< 0.001. Compliance with documentation of why procoagulant reversal agent was not given (CSTK-4) increased from 81.2% (n=39/48) to 94.1% (n=48/51), but the difference was not statistically significant OR =3.69 (95%CI 0.94 - 14.58), p=0.07.

Conclusion:
Use of structured data entry improves compliance with documentation of stroke standards and has immensely reduced abstraction times.
Abstract P841: The Impact of a Dedicated Pediatric Stroke Discharge Plan Upon Parent Preparedness for Clinic: Before and After the Start of Covid-19
Authors: Nederveld Cindy , Thompson Vivian , Murray Jacqueline , Armstrong Jennifer L , Barry Megan , Bernard Timothy J
Published: March 2021

Background:
The Colorado Pediatric Stroke Program provides comprehensive, multidisciplinary care for pediatric stroke patients and their families. The team, which includes dedicated inpatient and outpatient nurse coordinators, instituted a plan to support the transition from the inpatient to outpatient setting.

Purpose:
A survey was used to determine family preparedness for clinic and ease of scheduling their appointment. The data were collected before and after enacting remote scheduling and telehealth visits due to the COVID-19 pandemic.

Methods:
Our team provided educational materials and an outpatient appointment time to families at time of discharge starting in 2019. In January 2020, the stroke clinic staff surveyed parents and guardians about their preparedness for clinic. Telehealth encounters were initiated due to COVID-19 in March 2020, with staff conducting RedCAP surveys by telephone. The survey measured several components of visit preparedness and satisfaction including: understanding of diagnosis, reason for referral prior to clinic visit, familiarity with the stroke team prior to clinic visit, and ease in appointment scheduling. We compared results before and after March 2020 via two-tailed chi-square analysis or two-tailed Fischer’s test.

Results:
Prior to telehealth, families favorably reported responses with 92% (47/52) knowing the reason for referral, 86% (42/49) receiving educational material prior to clinic, and 84% (42/50) reporting familiarity with our team. All patients (50/50) reported that scheduling was easy. Only scheduling ease had a significant change during the pandemic, with 11% (2/11) of patients reporting difficulties with scheduling after starting telehealth (
P=0.03
).

Conclusion:
Childhood stroke is a disease with significant morbidity and mortality, requiring close follow-up care. Families report robust preparedness for clinic after the implementation of a comprehensive discharge plan. Although small numbers, remote scheduling and telehealth transition may present previously unseen barriers to scheduling during the pandemic. During abrupt changes in clinical operations additional scheduling resources may be needed to ensure continuity of care.
Abstract P844: The Use of Innovative Technology to Reduce Time of Notification Activation to Confirmation Response of Endovascular Team
Authors: Willett Melissa , Lee Brenda , Cherry Jane , Bruce Nhu , Newton Takiyah , Riley Krystle , Moye Stacy
Published: March 2021

Background:
It is well recognized that time to treatment inversely affects good outcome in acute stroke patients. The sooner patients are evaluated by a trained stroke physician, the more likely they will receive approved acute stroke treatments and interventions. At our Comprehensive Stroke Center, the code stroke team is made up of individuals and providers from multiple disciplines and in the activation of a code stroke, timing is the key element and we sought to improve this notification process through the use of a unifying single, alert system.

Purpose:
The goal of this project was to reduce our team activation time. We introduced an application called PerfectServe which allows for the entire stroke team to be alerted and the immediate notification of the neuro-interventional radiology team, when a suitable candidate is identified, without having to rely on a multistep process.

Methods:
Implementation of interventional radiology stroke intervention team using PerfectServe application notifications alongside our neurology and neuro-interventional radiology providers and enabling them to see real time updates of stroke patients and communicate plans of care. Retrospective analysis using a T-test analysis technique analyzed the data related to a one step process (PerfectServe application) and a previously utilized multiple step process (Everbridge application) times in minutes.

Results:
The one-step PerfectServe application significantly decreased the team notification alert to response confirmation by 10 minutes (
p
=0.05).

Conclusions:
The one-step PerfectServe application activation process provided more effective communication, team activation times, and better door to treatment times.
Abstract P845: Impact of T-Pa Pre-Pull Criteria in Collaboration With Telestroke Nurse
Authors: Snider Emily , Helms Anna Maria
Published: March 2021

Background and Purpose:
“Target: Stroke Phase III” aims to improve stroke outcomes through the reduction of door-to-needle (DTN) times within 60 minutes in 85% of cases. After a recent data review, DTN times exceeded 60 minutes in the majority of alteplase (t-PA) cases at facilities monitored by our Telestroke (TS) program. With our TS nurses (RNs) being a unique resource to quickly assess Code Stroke patients and identify eligibility for t-PA we were able to implement an ‘Alteplase Pre-Pull’ protocol to instruct the bedside staff to pull t-PA and have it at bedside prior to the teleneurologist’s assessment.

Methods:
Data was retrospectively collected from July-December 2019 (pre-mixed) and compared to data from January-June 2020 (pre-pulled). TS RNs were educated on pre-pull protocol titled “Less Than 3, Pull Me”. For patients presenting within three hours of symptom onset, TS RN would recommend bedside staff to pull t-PA and have at bedside: this would shave valuable minutes off DTN times if found to be t-PA eligible. TS RN would continue to assess for exclusions.

Results:
Significant improvements in DTN times due to pre-pulling t-PA. Average DTN time (total-241 patients July-December 2019) improved from 57 minutes to 51 minutes (231 patients Jan-June 2020). Average DTN for pre-pulled patients decreased by 3 minutes from 51 to 48 minutes. Average door to activation decreased from 12 to 7 minutes.

Conclusion:
Pre-pulling t-PA using the “Less Than 3, Pull Me” protocol significantly reduced DTN times by 6 minutes from 57 to 51 minutes. Activation-to-needle decreased by 1 minute from 46 to 45 minutes indicating that early activation leads to faster DTN times. Early recognition of symptoms by bedside staff is essential to decreasing DTN times. The second half of this study took place amid the COVID-19 pandemic impacting bedside staff due to limited resources. In summary, pre-pulling t-PA has allowed us to shave 6 life-saving minutes off DTN times equating to 11.4 million neurons (Puig, 2018).
Abstract P862: Successes and Impact of a Statewide Stroke Education Campaign for Healthcare Providers
Authors: Jones Olivia N , Pietrzak Janna , Picou Kylie , Cook Mindy , Santana Adela , Alexander Jerilyn , Reile Kirsten , RICHTER SAMANTHA , Quirk Lynde J , Carlblom Megan , Wiseman JuLann , Nissen Holly H , Johnson Sue , Khan Yosef
Published: March 2021

Introduction:
The North Dakota Mission: Lifeline Stroke program is a 3-year initiative which aims to improve statewide stroke systems of care. Due to complexities in recognizing and treating stroke patients, effective education of prehospital and hospital health care providers on guideline-based assessments and treatment methods were identified as an essential intervention. In person lectures, conferences, workshops, stroke simulation trainings, online courses, webinars, and a stroke certification program were deployed throughout the project.

Purpose:
The purpose of the post-education survey was to determine the impact, value, and success of different types of education provided during the project.

Methods:
North Dakota healthcare professionals (n=221) completed a 20-question online survey about their experiences participating in the stroke trainings provided from 2017 to 2020.

Results:
Survey respondents consisted of 76 Emergency Medical Service (EMS) providers and 145 hospital-based healthcare professionals. The majority of hospital-based staff respondents were nurses (80.1%), while most EMS-based respondents were paramedics or EMTs (75.0%). Half of all respondents (49.8%) participated in 2 or more educational offerings. Respondents were asked to rank the educational offerings in which they participated in by order of the benefit to their everyday practice. The two highest ranking educational offerings were the Advanced Stroke Life Support Class (mean rank=1.6) and Simulation in Motion (SIM) ND (mean rank=2.3). More than 90% of respondents stated that these trainings were extremely or very applicable to their everyday practice. When asked about the overall impact of all the educational offerings they participated in, almost all (92.6%) respondents indicated they agree that because of the trainings they have a better understanding of the key issues related to caring for stroke patients.

Conclusions:
Overall, the comprehensive survey provides concrete evidence and feedback that multi-modal education campaigns are well-received and effective in furthering awareness of guideline-based stroke assessments and treatment methods. Activities with a kinesthetic learning approach were found to be especially well-received.