bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract P788: Association Between Elevated Plasma Ykl-40 and Short, Long-Term Prognosis of Ischemic Stroke: From a Large Nationwide Stroke Registry
Authors: Qin Haiqiang , Liu Gaifen , Zhang Yijun , Yu Miaoxin , Wang Anxin , Zhang Guitao , Wang Yongjun
Published: March 2021

Aim:
YKL-40 is a novel biomarker that is associated with both acute and chronic inflammations. Elevated plasma concentrations of YKL-40 have been reported in patients with ischemic stroke. This study investigated the association of plasma YKL-40 concentrations at admission and short, long-term prognosis after ischemic stroke.

Methods:
This study is a prespecified biomarker sub-study of the third China National Stroke Registry (CNSR3), which is a prospective,national multi-center of 171 sites concerning consecutive patients of ischemic stroke and TIA within 7 days since onset with specimens collected at baseline. Plasma YKL-40 levels were detected by ELISA and patients were stratified into terciles according to Plasma YKL-40 concentrations. The multivariate Cox regression model was used to investigate the association of YKL-40 concentration and death and recurrence at 3 months, 6 months and 12 months after ischemic stroke, with potential confounders adjusted.

Results:
A total of 8013 first-ever ischemic stroke patients, with an average of 61.7±11.5 years, were included in this study. The YKL-40 concentrations of lower, middle and upper group were 30.36 ±8.53 mg/L, 64.89±13.49 mg/L, and 164.42±50.35 mg/L respectively. Higher YKL-40 concentration at admission was associated with combination events of death and recurrence, death as well as recurrence at 3-month, 6-month and 12-month since onset of ischemic stroke when compared with lower YKL-40 concentration. However, after adjusting for age, gender, smoking, drinking, hypertension, diabetes, low-density lipoprotein, and C-reactive protein, higher YKL-40 concentration at admission was just statistically associated with combination events and death, but not stroke recurrence at 3-month, 6-month and 12-month when compared with lower YKL-40 concentration (table 1).

Conclusions:
The elevated YKL-40 at admission was associated with short and long-term death, but not recurrence after ischemic stroke.
Abstract P793: Extracellular Vesicles Enhance Blood-Brain Barrier Integrity by Nf-κB Dependent Regulation of Abcb1 in Stroke Mice
Authors: Zhang Lin , Kuang Yaoyun , Zheng Xuan , Psychogios Marios , Doeppner Thorsten R
Published: March 2021

Extracellular vesicles (EVs) derived from neural progenitor cells (NPCs) enhance post-stroke neurological recovery, albeit the underlying mechanisms remain elusive. Since previous research described an enhanced post-stroke integrity of the blood-brain barrier (BBB) upon systemic transplantation of NPCs, we wondered if NPC-derived EVs affect BBB stability and which cellular mechanisms might be involved in the process. Using an in vitro co-culture model of brain endothelial cells (ECs) and astrocytes, cells were treated with EVs or PBS and exposed to oxygen-glucose-deprivation (OGD) injury. The readout parameters focused on the expression of ABCB1, an ATP-binding cassette (ABC) transporter expressed on ECs contributing to BBB integrity. Further in vitro analysis examined the pro-inflammatory NF-κB pathway, the permeability and the transcellular electrical resistance (TER) of cultured ECs. In vitro data was finally confirmed using a rodent stroke model. Cultured ECs displayed increased ABCB1 levels when exposed to OGD, which was reversed by treatment with EVs. The latter was due to an EV-induced inhibition of the NF-κB pathway. Using a BBB co-culture model of ECs and astrocytes exposed to OGD, EVs stabilized the BBB and ABCB1 levels without affecting TER. Likewise, EVs yielded reduced Evans blue extravasation, decreased ABCB1 expression as well as an inhibition of the NF-κB pathway and downstream matrix metalloprotease-9 activity in stroke mice. The EV-induced inhibition of the NF-κB pathway resulted in a post-stroke modulation of immune responses. Our findings suggest that EVs enhance post-stroke BBB integrity via ABCB1 and MMP-9 regulation, attenuating inflammatory cell recruitment by inhibition of the NF-κB pathway.
Abstract P795: Activating Transcription Factor 3 Improves Stroke Recovery Through Reduction of Neuronal Damage and Neuroinflammation
Authors: Wang Zhanqiang , Pan Peipei , Liang Rich , Li Qifeng , Pan Janothon , Guan Zhonghui , Su Hua
Published: March 2021

Background and Purpose:
Activating transcription factor 3 (ATF3), a member of the ATF/CREB family, is upregulated in the early phase of various stresses including ischemic stroke. The role of ATF3 in ischemic stroke injury has not been fully elucidated.

Hypothesis:
ATF3 improves stroke outcomes through reduction of neuronal damage and neuroinflammation.

Methods:
Permanent distal middle cerebral artery occlusion (pMCAO) was performed in 8-week-old male and female C57BL/6J (WT) and ATF3 knockout (ATF3
-/-
) mice. The sensorimotor functions were analyzed 3 days after pMCAO through adhesive removal and corner tests. Infarct volumes and injured neurons were quantified on Nissl stained and Fluoro-Jade C (FJC) stained sections. The cell-specific expression of ATF3 was analyzed by co-staining ATF3 antibody with antibodies specific to NeuN (Neuron), CD68 (microglia/macrophage) and GFAP (astrocyte). The expression of ATF3 in injured neurons was analyzed by ATF3 and FJC double labeling.

Results:
ATF3 expression was detected exclusively in neurons in the infarct area 1 day after pMCAO. There were a few ATF3
+
CD68
+
microglia/macrophages at the peri-infarct regions 2 and 3 days after pMCAO. Almost all FJC
+
neurons were ATF3 positive. No ATF3 expression was detected in astrocytes. Compared to WT mice, ATF3
-/-
mice took longer time to remove the adhesive from their right paws (p<0.001) in adhesive removal test and more left turns in corner test (p<0.001) 3 days after pMCAO. ATF3
-/-
mice also had a larger infarct volume (p = 0.014), more FJC
+
neurons (p=0.002) and CD68
+
microglia/macrophages (p=0.003) in the peri-infarct regions than WT mice.

Conclusions:
Deletion of ATF3 exacerbates neuronal injury, neuroinflammation, and sensorimotor dysfunction in stroke mice, suggesting that upregulation of ATF3 at early stage of stroke improves ischemic stroke recovery through reduction of neuronal damage and neuroinflammation.
Abstract P796: Integrated Analysis of Gait Parameters and Gene Expression Profiles in a Murine Model of Subarachnoid Hemorrhage
Authors: Wong George K
Published: March 2021

Objective:
Gait variability analysis has been adopted in clinical settings to characterize the presentation of various neurological diseases. However, literature and practice lack a comprehensive murine model assessment of the gait deficits that result from subarachnoid hemorrhage (SAH). Further, correlations between gait parameters and the gene expression profiles associated with SAH have yet to be identified. The present study quantitatively assesses gait deficits through a clinically relevant murine model of SAH to determine associations between gait deficits and SAH-related gene expressions.

Methods:
A total of 159 dynamic and static gait parameters from the endovascular perforation murine model for simulating clinical human SAH were measured using the CatWalk system. Pearson’s correlation analysis was applied, and 88 genes associated with SAH were identified from the Ingenuity Pathway Analysis database to aid the investigation of the relationship between gait variability and gene expression profiles.

Results:
Eighty gait parameters and the mRNA expression levels of 35 of the 88 SAH-associated genes exhibited significant change in the SAH models (p < 0.05). Totals of 42 and 38 gait parameters correlated with the 35 SAH-associated genes positively and negatively with Pearson’s correlation coefficients of > 0.7 and < -0.7, respectively. p-SP1
453
expression in the motor cortex in SAH animal models displays a significant correlation with a subset of gait parameters associated with muscular strength and coordination of limb movements.

Conclusion:
This examination of gait variability and its strong correlation to gene expression profiles provides a quantitative and reliable assessment of the SAH model’s motor performance. This research provides valuable insights into the study of disease progression and offers novel therapeutic interventions in the murine modeling of SAH. p-SP1
453
expression could act as a biomarker to monitor SAH pathological development and a therapeutic target for SAH.
Abstract P798: Antimicrobial Protein Reg3a and Network Inflammatory Proteins Are Predictive of Infarct Volume and Functional Impairment in Ischemic Stroke
Authors: Sands Madison , Frank Jacqueline , McLouth Chris , Maglinger Benton , Roberts Jill , Trout Amanda L , Grupke Stephen , Stowe Ann M , Fraser Justin , Pennypacker Keith R
Published: March 2021

Introduction:
Regenerating Family Member 3 Alpha (REG3A) is an antimicrobial protein secreted by the intestine and pancreas. REG3A is involved in immune-mediated inflammatory responses and helps maintain homeostasis of the gut microbiome. REG3A is elevated in patients with ischemic stroke, but its role within the gut-brain axis during stroke remains unclear. Our aim was to examine the association of plasma REG3A levels with other signaling proteins in systemic plasma during stroke, and its correlation with clinical outcomes of ischemic stroke.

Methods:
Intracranial and systemic plasma samples from n=25 thrombectomy subjects underwent Proximity Extension Assay via Olink Proteomics. REG3A levels and inflammatory markers were examined using bivariate regressions. Stepwise regression determined the predictability of infarct volume by REG3A. Two-tailed t-tests were used to examine the relationship between the National Institutes of Health Stroke Scale (NIHSS) and levels of REG3A.

Results:
Increased expression of systemic REG3A correlated with increases in infarct volume (p=.009, R=.514). Stepwise regression predicting infarct volume yielded a model including REG3A and systemic proteins such as CCL19, IL15, and IL1α (P<.001, R=.980). NIHSS scores corresponding to moderate-severe/severe strokes had increased intracranial REG3A (p<.05) and increased ratios of intracranial:systemic REG3A expression (p=.05).

Conclusions:
Within a network of proteins, REG3A is predictive of increased infarct volume and decreased function. Studies suggest that IL17 and IL6 induce REG3A expression. Subsequent REG3A can interact with NFkB, which transcriptionally regulates CCL19, IL1α, and IL15. In the intestine, REG3A regulates microbial synthesis of fatty acids and inflammatory processes. Fatty acids suppress cytokines such as IL6 and IL1α and are reportedly neuroprotective in stroke. Increase of systemic REG3A may reflect cellular responses to gut dysbiosis and inflammation triggered from ischemic stroke. Future studies will examine prognostic and therapeutic potential of the REG3A pathway in large vessel occlusive stroke.
Abstract P799: Nicotine Along With Oral Contraceptive Exposure Alters Brain Lipid Metabolism and Exacerbates Ischemic Injury in Female Rats
Authors: Siegel Jonathan , Diaz Francisca , Raval Ami P
Published: March 2021

Background:
Smoking-derived nicotine (N) and oral contraceptives (OC) synergistically exacerbate both global and focal ischemic brain damage in females. While the underlying mechanisms remain elusive, our published study showed that OC exacerbate N toxicity via altered mitochondrial electron transport chain function. Because mitochondria play a central role in cellular metabolism, we examined the metabolic fingerprint of adolescent and adult female rat brains exposed to N +/- OC.

Methods:
Adolescent (6 weeks old) and adult (12 weeks old) Sprague-Dawley female rats were randomly (n = 8/group) exposed to either saline, N (4.5 mg/kg) +/- OC for 16-21 days. Following treatment, brain tissue was harvested for unbias metabolomic analysis (performed by Metabolon Inc.). The metabolomic profile was complemented with western blot analysis and enzyme activity measurements.

Results:
Pathway enrichment analysis showed significant alterations in lipid metabolism. Adolescent but not adult females treated with N, OC and N+OC compared to saline showed significant increases in carnitine conjugated fatty acid metabolites such as arachidonoylcarnitine (C20:4), docosahexaenoylcarnitine (C22:6) and stearoylcarnitine (C18). These changes in fatty acyl carnitines were accompanied by an increase in a subset of free fatty acids, suggesting elevated fatty acid β-oxidation in the mitochondria to meet energy demand. In support, 3-hydroxybutyrate (BHBA) was significantly lower in OC and N+OC treatment group in adolescent animals, implying a complete shunting of acetyl CoA for energy production via TCA cycle. BHBA is a ketone body that increases in concentration as lipid oxidation rates increase with acetyl CoA accumulation. Reduced BHBA levels may also suggest mitochondrial dysfunction in response to OC and N+OC treatment.

Conclusion:
The observed changes in the metabolic fingerprint and fatty acid metabolism reflect a general alteration in energy metabolism with nicotine treatment exclusively in young animals and these changes are enhanced by N+OC treatment. Discerning the exact effects of N +/- OC on overall brain metabolism and the molecular mechanisms affecting mitochondrial function at different ages will open a new window for future therapeutic intervention.
Abstract P803: Pituitary Adenylate Cyclase-Activating Polypeptide via Cyclic-AMP Inhibits Nogo-A by Internalizing Its Receptor NgR1
Authors: GOPALAKRISHNA Rayudu , Lin Charlotte Y , Oh Andrew , Mack William J
Published: March 2021

Introduction:
After a stroke, axonal regeneration is inhibited by diverse axonal growth inhibitors, such as Nogo-A. They bind to the Nogo-A receptor 1 (NgR1) and induce the collapse of growth cones and inhibit neurite outgrowth. Since NgR1 is the receptor for a variety of axonal growth inhibitors, it is a crucial target for the prevention of axonal growth inhibition. Pituitary adenylate cyclase-activating polypeptide (PACAP) has neuroprotective and neurotrophic activities and increases neuritogenesis and synaptic plasticity. It enhances functional recovery after stroke in various animal models.

Methods:
Neuroscreen-1 (NS-1) cells were selected for this study as they produce rapid and robust neurite outgrowth with NGF. Cell surface NgR1 was detected using the indirect immunofluorescence method. The internalization of NgR1 was quantitated using the biotinylation method and Western immunoblotting.

Results:
Using the indirect immunofluorescence method, we found that PACAP (PACAP-38) induced a rapid decrease in the cell surface expression of NgR1 in NS-1 cells. The biotinylation method revealed that PACAP induced the internalization of NgR1. This internalization of NgR1 was blocked by pretreatment of NS-1 cells with SQ 22536, an inhibitor for adenylate cyclase, suggesting that cAMP plays a crucial role in the internalization of NgR1. The protein kinase A (PKA)-specific inhibitor KT5720 did not block PACAP-induced NgR1 internalization, whereas the exchange protein directly activated by cAMP (Epac)-specific inhibitor ESI-09 blocked this internalization. Collectively, this data suggests that PACAP-induced NgR1 internalization is independent of PKA but is dependent on Epac. The PACAP-induced decrease in cell surface expression of NgR1 and its internalization desensitized NS-1 cells to Nogo-66-induced growth cone collapse and enhanced neuritogenesis.

Conclusion:
Cyclic-AMP and Epac are involved in the PACAP-induced desensitization of neuronal cells to Nogo-A and increase in neuritogenesis. Since PACAP crosses the blood-brain barrier, it may be a useful therapeutic agent to overcome axonal growth inhibitors and enhance functional recovery after stroke.
Abstract P806: Sirtuin1 Plays a Critical Role in Reversing Skeletal Muscle Atrophy in Cerebral Ischemic Stroke
Authors: Mohamed Junaith S , Ferrandi Peter J , Hector Paez G , Pitzer Christopher R , Alway Stephen E
Published: March 2021

Stroke is a leading cause of mortality and long-term disability in patients worldwide. Skeletal muscle is the primary systemic target organ of stroke that severely induces muscle wasting and weakness, which contributes more to the long-term functional disability in stroke patients than any other disease. Currently, no approved pharmacological drug is available to treat stroke-induced muscle loss. Rehabilitative therapy is the only available option to improve muscle function in stroke patients. However, higher muscle fatigability and lower muscle strength from extensive muscle wasting in post-stroke patients provide poor rehabilitative outcomes. As a result, about two-thirds of stroke survivors persist in a state of insufficient recovery and experience physical disability that drastically reduces their health and quality of life. The major challenge in the drug discovery effort for treating post-stroke muscle wasting is the lack of our understanding of the molecular and/or cellular mechanisms that underlie the muscle wasting in stroke. To understand the molecular origin of stroke-induced muscle atrophy, gene expression profiling and associated biological pathway enrichment studies were performed in a mouse model of cerebral ischemic stroke using high-throughput RNA sequencing and extensive bioinformatic analyses. RNA-seq data revealed that the elevated atrophy in skeletal muscle observed in response to stroke was primairly associated with the altered expression of genes involved in the muscle protein degradation pathway. Further analysis of RNA-seq data identified Sirtuin1 (SirT1) as a critical protein that plays a significant role in regulating post-stroke muscle mass. SirT1 gain-of-function in skeletal muscle significantly reversed stroke-induced muscle atrophy
via
inhibiting the activation of the ubiquitin proteasomal pathway and restoring autophagy function. Collectively, this study identified suppression of SirT1as a novel mechanism by which stroke induces muscle atrophy.
Abstract P807: Vitamin B12 Deficiency Impairs Balance and Coordination After Photothrombotic Damage to the Sensorimotor Cortex in Adult Male and Female Mice After Ischemic Stroke
Authors: Yahn Gyllian , Bottiglieri Teodoro , Wasek Brandi , Jadavji Nafisa
Published: March 2021

Introduction:
The majority of the world’s population is growing older, in 2000, 10% of the total population of the world was over 60 years old and is projected to increase to 21% by 2050. Brain vasculature is unique, and its aging has been scarcely investigated at the cellular, and molecular levels, as well as in the context of age-related comorbidities. Nutrition is a modifiable risk factor for stroke, as people age their ability to absorb some nutrients decreases. A primary example is vitamin B12, the majority of older adults are deficient in vitamin B12 because of changes in breakdown and absorption of the vitamin. Furthermore, a vitamin B12 deficiency results in elevated levels of homocysteine which is a risk factor for cardiovascular diseases, such as stroke. Using a mouse model system, the aim of this study was to understand the role of vitamin B12 deficiency in ischemic stroke outcome and investigate mechanistic changes in the brain.

Hypothesis:
Vitamin B12 deficient mice will exhibit worse stroke outcome compared to control diet mice through increased apoptosis.

Methods:
At 10-weeks of age male and female C57Bl/6J mice were put on control (0.025 mg/kg of vitamin B12) or vitamin B12 deficient (0 mg/kg of vitamin B12) diets for 4-weeks prior to ischemic damage. At 14 weeks of age we induced ischemic stroke in the sensorimotor cortex using the photothrombosis model, all animals received damage. Animals continued on diets for 4 weeks after damage. At 18 weeks of age we assessed stroke outcome using the accelerating rotarod and forepaw placement task. After the collection of behavioral data, we euthanized animals and collected brain and liver tissue to assess histological and biochemical measurements. Plasma was used to measure total homocysteine and methylmalonic acid.

Results:
All animals maintained on the vitamin B12 deficient diet had increased levels of total homocysteine in plasma and liver tissue. Male and female mice maintained on a vitamin B12 deficient diet had impairments in balance and coordination on the accelerating rotarod compared to animals maintained on a control diet.

Conclusions:
Vitamin B12 deficiency impacts motor function in older adult male and female mice. We are investigating damage volume and potential mechanisms within the damage brain tissue.
Abstract P810: Dysregulation of Dipeptidyl Peptidase and Adipokines in Atherosclerosis and Ischemic Stroke
Authors: Wesley Umadevi V , SUTTON IAN , Lang McDaniel , Dempsey Robert J
Published: March 2021

Introduction:
Atherosclerosis and stroke remain the leading causes of death and functional disabilities. Stable carotid atherosclerosis (CA) plaques can rupture inducing ischemic stroke and functional impairment. However, there are gaps in our understanding of the molecular factors in cerebro-vascular diseases.

Methods:
Using pre-clinical animal models of atherosclerosis and ischemic stroke, we investigated the association of specific proteases and adipokines using cellular, molecular, proteomic, and biochemical approaches. We analyzed blood, brain, and aortic tissues obtained from wildtype, normal and high fat diet fed APO-E deficient mice with and without plaques, and . We examined the differential expression of levels of DPPIV and adipokines in plasma using a targeted proteome profiler antibody array. The levels of mRNA were assessed in APOE-/- aortic and brain tissues using pathway specific PCR arrays.

Results:
In a pre-clinical animal model of focal ischemic stroke, we found that DPPIV is significantly increased in the ischemic brain. Genetic ablation of DPPIV gene, decreased the ischemic brain infarct size in a middle cerebral artery occlusion induced ischemic mouse model. Furthermore, we observed upregulation of DPPIV expression in aortic root lesions and carotid arteries of atherogenic apolipoprotein E deficient (ApoE-/-) mice as compared to wild type animals. Circulating DPPIV levels in plasma were also significantly higher in ApoE-/- and stroke induced animals. In the plaque tissue, DPPIV was over-expressed in macrophages as indicated by its co-localization with Mac-2, and in endothelial cells (EC). Oxygen glucose deprivation induced in vitro ischemia also upregulated DPPIV expression in macrophages and EC. DPPIV decreased EC viability/mitochondrial potential, and disrupted endothelial function as shown by impaired pro-angiogenic structure formation. DPPIV expression was associated with increased levels of apoptotic and inflammatory adipokines/cytokines.

Conclusion:
DPPIV and adipokine dysregulation is associated with atherosclerosis and ischemic stroke. Imbalanced production of these factors may further worsen post-stroke outcome, and are potential targets for clinical intervention.
Abstract P811: Oral Curcumin Treatment Facilitates Recovery of Function in a Rhesus Monkey Model of Cortical Injury
Authors: Pessina Monica A , Bowley Bethany G , Medalla Maria , Rosene Douglas L , Moore Tara L
Published: March 2021

Curcumin is a primary component of the spice turmeric, and is a potent anti-inflammatory and anti-oxidant compound. In rodent models of brain damage from stroke or trauma, curcumin acts primarily on microglia and astrocytes to inhibit pro-inflammatory signaling pathways and to reduce inflammation and levels of reactive oxygen species (ROS). Further, rats with cortical injury treated with curcumin have smaller lesions and fewer neurological impairments than those treated with vehicle. However, it is not clear whether curcumin exerts the same biological effect in primate brains as in rodent brains, and the effects of curcumin have not yet been extensively tested in monkey models of brain injury. Data from our laboratory has demonstrated that curcumin enhances spatial working memory and motor function in normal aging rhesus monkeys given daily doses of dietary curcumin over two years. The question remains as to whether chronic dietary curcumin can enhance neuroprotection and dampen or ameliorate functional motor deficits after cortical injury. Thus, we administered curcumin to adult, male rhesus monkeys daily for two weeks prior to and 12 weeks following induced cortical injury to the hand-representation of primary motor cortex (M1). Monkeys given daily treatment with oral doses of curcumin, but not those given vehicle, demonstrated significantly enhanced recovery of function in terms of time to retrieve a food reward on our hand dexterity task (HDT). In addition, treated monkeys returned to pre-injury finger-thumb grasp patterns on the HDT, while monkeys that received vehicle developed a compensatory whole hand grasp pattern and never returned to pre-injury grasp. These findings provide evidence that the anti-inflammatory compound, curcumin, is an effective treatment for facilitating recovery of function following cortical injury. Studies investigating the effect of curcumin on the microglia and astrocytes in the brains from these monkeys will provide evidence of the role of curcumin in reducing inflammation and ROS following injury.
Abstract P815: Decoding the Cross-Talk Between Grafted Neural Stem Cells and Host Brain to Predict the Molecular Mechanisms of Stem Cell-Induced Functional Recovery After Stroke
Authors: Tigchelaar Seth S , Azevedo-Pereira Ricardo L , Dong Chen , liang xibin , Bliss Tonya , Steinberg Gary
Published: March 2021

Stroke is a leading cause of long-term disability and death in the united states. The development of new therapies for stroke are sorely needed. There is great hope that stem cell therapy will create a paradigm shift in the treatment of stroke patients. A barrier to ensuring clinical success of stem cell therapy is the paucity of understanding of the mechanisms by which stem cells exert their beneficial effects. Using a novel mRNA purification method, we identified 50 genes encoding extracellular space proteins, expressed by human neural stem cells (hNSCs) whose expression positively correlated with functional recovery. In this study, we focus on one of the paracrine factors from grafted hNSCs that correlated best with functional recovery, to investigate its therapeutic potential in promoting recovery after stroke.

Male nude rats underwent stroke using the distal middle cerebral artery occlusion (dMCAo) model. One week following stroke, osmotic pumps were prepared and loaded with recombinant MTN-2. The osmotic pumps were inserted into the peri-infarct area and infused recombinant MTN-2 for 5 days. Post-stroke, animals were assessed for functional recovery for 5 weeks using both the Montoya staircase test and the whisker-paw reflex test to assess for forelimb function, dexterity, side bias, and placing deficits.

After 5 weeks, brain tissue was isolated to assess glial cell morphology. Brain sections were stained with GFAP and IBA1 to visualize astrocytes and microglia, respectively. Confocal images were processed and analyzed using the Bitplane Imaris image analysis software. Output measurements of number of cells/mm2, cell volume, cell branching, and process length and thickness were obtained to characterize the changes in astrocytic and microglial response to injury and paracrine factor treatment.

By identifying paracrine factors that are responsible for the regeneration of brain tissue following implantation of hNSCs in stroke brain, this work will increase the likelihood of successful clinical translation of stem cell therapy for stroke. Moreover, elucidating these molecular pathways important for brain recovery may ultimately identify novel therapeutic targets and offer hope to millions of Americans who live with the devastating effects of stroke.
Abstract P816: Nurse-Driven Rapid Covid-19 Testing in Emergency Department Stroke Patients
Authors: Aggabao Stacey , Thorsen Tawnae , Gupta Atul , Dhanji Raeesa , Gaffney Denise , McCartney David L , Mkrtumyan Alvina , Punsalang Lorina , Le Duy , Ajani Zahra , Cheng Pamela , Cline Trevor E , Sangha Navdeep S
Published: March 2021

Introduction:
The COVID-19 pandemic presents obstacles to time sensitive emergencies, such as stroke care. In acute strokes, knowing the COVID-19 status may help to preserve personal protective equipment (PPE) in patients in whom a thrombectomy may be indicated and helps to decrease unnecessary exposure. This study aims to demonstrate that rapid evaluation of a patient’s COVID-19 status is feasible without delaying treatment times.

Methods:
An intradisciplinary team was convened to create a workflow for rapid COVID-19 testing. The Abbott Rapid® COVID-19 swab kit and assay were stocked in the ED Pyxis, utilizing the narcotic count feature to ensure all swabs were accounted. Upon activation of Code Stroke, the ED RN donned PPE and swabbed the patient’s naso-oral pharynx. The collected swab was labeled, placed in a bio-hazard bag, sanitized and handed to a second RN outside of the room. The specimen was taken to a pre-alerted lab technician who prepped the assay after hearing the code stroke. After specimen collection, the patient followed the normal code stroke pathway and was taken to the CT scanner. Metrics were analyzed for the pre COVID-19 (January through April) and during active COVID-19 (May through July) periods.

Results:
There were 136 code strokes from January thru July 2020. 81 were during pre-COVID vs. 55 during active-COVID. 47 of 55 (96%) were swabbed, 2 (4%) of whom were positive. There was no difference between pre-COVID and active-COVID door to CT initiated time (16 mins [IQR 13-24] vs. 22 mins [IQR 13-25] p=0.75), door to CT resulted time (21 mins [IQR 15-26]) vs. 23 mins [IQR 16-29] p=0.63). 18 patients received tPA pre-COVID and 5 during active-COVID with no difference in DTN (pre: 37.5 mins [IQR 30-43] vs. active: 28 mins {IQR 26-41] p=0.37). Door to CT initiated was faster for those who had their COVID swab performed pre-CT (14 mins [IQR 11.5-16.5] p=0.034) vs. post-CT (20 mins [IQR 17-28]). Likewise, door to CT resulted was also faster pre-CT: 24 mins [IQR 19-32] vs. post-CT: 17 mins [IQR 15-23] (p=0.04).

Conclusion:
The COVID-19 rapid swab code stroke process was feasible and did not delay treatment times.
Abstract P817: The Mediation Effects of Perceived Social Support on the Association Between Optimism and Depressive Symptoms Among the Stroke Survivors and Caregiver Dyads
Authors: Chung Misook L , Miller Jennifer L , Lee Suk Jeong , King Rosemarie B
Published: March 2021

Background:
Depressive symptoms are a common psychological outcome in post-stroke management among stroke survivors and their caregivers. Optimism and social support are known to protect against depressive symptoms. However, little is know about how optimism and perceived social support contribute to depressive symptoms among stroke survivor-caregiver dyads. The purpose of this study was to examine the mediating effect of perceived social support on the relationship between optimism and depressive symptoms among stroke-survivor and caregiver dyads.

Methods:
A total of 105 stroke survivor and caregiver dyads completed a survey two years after first stroke. Depressive symptoms, optimism, and perceived social support were assessed using the Center for Epidemiologic Studies-Depression, the Revised Life Orientation Test, and the Interpersonal Support Evaluation List. The dyadic actor-partner interdependence mediation analysis with distinguishable dyads was used to test the mediation effect on dyadic data.

Results:
Stroke survivors (mean age 58.7 years, 56% male) and their caregivers (mean age 56.7 years, 61% female) reported similar levels of depressive symptoms, optimism, and perceived social support,. Figure 1 presents the results. Individuals with higher levels of optimism had higher levels of perceived social support. Higher levels of optimism in caregivers were significantly associated with lower levels of depressive symptoms of both caregivers and stroke survivors. Perceived social support significantly mediated the relationship between optimism and depressive symptoms for stroke survivors. Caregivers’ perceived social support was also a significant mediator between caregivers’ optimism and stroke survivors’ depressive symptoms.

Conclusion:
The findings suggest that interventions to improve dyad members’ social support would be beneficial to improve depressive symptoms of dyad members even for those who have lower levels of optimism.
Abstract P819: Individualized Patients’ Risk of Post Rt-pa ICH in Acute Ischemic Stroke by Using a Simple Predictive Model
Authors: Pengtong Waitayaporn , Kongmuangpak Mananchaya , Noitamyae Niraya , Hiranshayangoon Nongnapas , Sriprayoon Pimchanok , Wongmayurachat Kanokkarn , Nittayaboon Kittiya , Nopmaneejumruslers Cherdchai , Nilanont Yongchai
Published: March 2021

Background and Purpose:
A simple and reliable prediction of post intravenous recombination tissue plasminogen activator (rt-PA) intracerebral hemorrhage (ICH) is useful for stroke team to inform individual risk and improve hospitalization care. We aim to develop and validate a simple predictive score model to assess the 24-hour risk of ICH post rt-PA.

Methods:
This retrospective study included 739 acute ischemic stroke patients who received intravenous rt-PA between October 2005 and June 2020 at Siriraj Hospital, Bangkok, Thailand. Multiple logistic regression was used to evaluate the value of independent variables associated with any ICH and symptomatic intracerebral hemorrhage (SICH) measure by the European Cooperative Acute Stroke Study II (ECASS II) definition. Adjusted ORs of independent variables were converted to point score, summated of point score provide a probability of ICH and SICH. The predictive scores were internal validated in 95 patients and performance tested with an area under a receiver operating characteristic curve (AUC-ROC).

Results:
From a total of 739 patients, 19.2% had an ICH in which 5.9% was SICH. The predictive model of ICH included hyperdense middle cerebral artery sign (HDMCA) (3 points), initial blood glucose > 180mg/dl (3 points), coronary artery disease (CAD) (2 points), international normalized ratio (INR) > 1.0 (2 points) and 10 year increase of age ( 1 point per 10 year increase; age ≤ 20 year = 1). The performance of the predictive model showed AUC-ROC was 0.72 (95% confidence interval, 0.60 - 0.82) in the derivative cohort and AUC-ROC was 0.74 (95% confidence interval, 0.66 - 0.85) in the validation cohort.

Conclusions:
This simple predictive model provides a better prediction of a 24-hour risk of ICH post rt-PA in AIS among Thai patients. An individualized ICH risk post rt-PA can assist frontline physicians and relatives in rt-PA decision making process. Further external validation and prospectively confirmed in a larger cohort is recommend.
Abstract P820: Fast Prediction of the Dysphagia Severity Using Clinical Signs in Acute Ischemic Stroke Patients
Authors: Ye Ting , Dong Yi , Huang Shengyan
Published: March 2021

Objective:
The purpose of this study was to compare the clinical signs in patients with acute ischemic stroke(AIS) and identify which of them was associated with the severity of dysphagia.

Methods:
This was a prospective observational study enrolled AIS within 14 onset days. All patients had swallowing evaluations by the modified Volume Viscosity Swallowing Test (the modified V-VST). Five clinical signs suggestive of swallow function impaired were directly observed in the patients who failed the test. We compared the performance of clinical signs between different completing volumes at three viscosity series. The area under curves (AUCs) were made to show the ability of specific clinical signs in predicting the dysphagia severity in patients with AIS.

Results:
184 hospital-based AIS patients who failed the modified V-VST were enrolled from June 2017 to December 2019. 123 patients were identified as moderate swallow function impaired and 61 patients were identified as serious. Larynx movement and tongue movement were significant different clinical signs at all of three viscosities (p≤0.001). The AUC of larynx movement in predicting severity of dysphagia was 0.733( 95% CI 0.658-0.808,P<0.001).

Conclusions:
Larynx movement and tongue movement were easy clinical signs for medical staffs to assess the dysphagia severity quickly. Additionally, larynx movement showed stronger ability to predict the severity of dysphagia in AIS patients.
Abstract P821: A New Era for Cerebral Angiograms: TransRadial Approach in NeuroInterventional Radiology
Authors: Gasparovic Taylor , Cook Sarah M , Morrow Benjamin , Roach Eileen , Spiering Kate , Henry Stephanie
Published: March 2021

Background:
Historically, femoral artery access has been the standard for neurointerventional radiology (NIR) procedures. However, recent advances in cerebral angiography have resulted in new arterial access locations, such as the TransRadial (TR) approach which has become more frequently utilized by proceduralists at our facility. This change necessitates staff competency when caring for TR-approach patients. In 2019, our facility received a recommendation for improvement (RFI) from The Joint Commission during the Comprehensive Stroke Center recertification survey related to incomplete post-TR-approach documentation. Upon initiation of TR-approach documentation audits, the team discovered documentation compliance rates of 46.2% for both TR wristband deflation volumes and wristband removal.

Purpose:
Due to the lack of knowledge associated with the novel TR-approach, the purpose of this project was to standardize post-NIR nursing care for patients who underwent a TR-approach cerebral angiogram. The goal was to observe a 25% increase in TR-approach care documentation elements by January 2020.

Methods:
Education created by the NIR manager was shared with nursing leadership and bedside nursing staff. Audits completed by the stroke quality nurse and NIR manager immediately followed to measure compliance with documentation of TR wristband deflation volumes and wristband removal. The NIR team collaborated with informatics leadership to develop a NIR documentation band within our electronic documentation system, resulting in a centralized location for documentation of all required TR-approach details. The two items specifically lacking compliance were included in the NIR documentation band build.

Results:
Audits demonstrated a 28.4% increase in compliance of TR wristband removal documentation and an 18.6% increase in compliance in TR wristband deflation protocol documentation.

Conclusion:
As a result of the RFI, our facility developed a protocol for post-TR-approach nursing care that can ultimately improve patient safety and outcomes, as well as be easily replicated at other facilities seeking to improve NIR patient care.
Abstract P822: In-Hospital Stroke Treated With IV tPA at a Comprehensive Stroke Center Compared to Primary Stroke Centers Pre and Post Telestroke Implementation
Authors: Khrlobyan Manya , Shi Jiaxiao M , Ajani Zahra , Le Duy , Cheng Pamela , Rho Howard J , Ly An , Gaffney Denise , Sangha Navdeep S
Published: March 2021

Introduction:
In-hospital strokes (IHS) often have delayed recognition time and a delay in physician assessment, playing a role in unfavorable outcomes. Telestroke (TS) participation is linked to lower odds of hospital mortality and is safe and effective in treating acute ischemic stroke. We implemented a TS program for IHS patients at primary stroke centers (PSC) and assessed tPA time metrics, complications and 90-day functional outcomes as compared to a robust in hospital stroke system of care at a comprehensive stroke center (CSC).

Methods:
Using a network database, data for all in-hospital code strokes were retrospectively abstracted between 2010-2020 at a CSC and 11 PSC’s. The CSC was compared to PSC’s pre and post implementation of a TS program. Data were analyzed using Wilcoxon rank-sum test, chi-square and exact tests.

Results:
We identified 193 patients, 77 at the CSC, 71 at pre-tele PSC’s, and 45 at post-tele PSC’s. Symptom-recognition-time (SRT) to neurology evaluation (median 15min {IQR 10-27} vs 75min {IQR 45-126, p=<0.0001) and SRT to IV t-PA (median 65min {IQR 46-91} vs 94min {IQR 73-112}, p=<0.001) were all faster at the CSC vs pre-tele PSC’s. There was no difference in rate of complications (p=0.05). When stroke mimics were excluded, CSC patients had a favorable 90-day mRS of 0-1 (24 patients, 35% vs 11 patients, 19%, p=0.04). After implementation of TS at PSC’s, there was no difference in tPA time metrics, except SRT to neurology evaluation remained faster at CSC (median 15min {IQR 10-27} vs 31min {IQR 18.5-52.5}, p=0.0002). There was no difference in rate of complications (p=0.21) and mRS at 90 days (p=0.82).

Conclusions:
Implementation of a TS program for IHS at PSC’s may improve tPA time metrics and 90 functional outcomes to the standards of CSC’s without increasing complication rates. Our study was limited by retrospective design and small sample size.
Abstract P824: Ready, Set, Go! Covid-19 Pandemic Drives Creation of Fast Track Alteplase Protocol
Authors: Cook Sarah M , Spiering Kate , Roach Eileen , Molyneaux Bradley , Henry Stephanie
Published: March 2021

Background:
In response to the pandemic, our facility recognized the need to safely decompress ICUs to create space for critically ill COVID-19 patients. Stroke leadership identified select recipients of Alteplase to have care safely de-escalated from ICU to stepdown status earlier than the traditional protocol allowed. Per previous protocol, all stroke patients recovered in ICU for 24 hours post-Alteplase with 36 neurological and vital sign assessments completed. Acting upon the need to ensure patient safety and create inpatient ICU bed availability, the multidisciplinary stroke leadership team created the Fast Track Alteplase Protocol.

Goals:
Project goals included decreasing ICU utilization and minimizing nursing encounters at the patient bedside to decrease potential COVID-19 exposures.

Methods:
Protocol qualifications include both pre-Alteplase NIH Stroke Scale scores less than 10 and no large vessel occlusions or flow limiting stenosis present on imaging. Once in the protocol, to qualify for transfer out of ICU, an NIH Stroke Scale score less than 10 throughout ICU stay, non-contrast head CT or MRI to evaluate infarct burden, not require continuous anti-hypertensive medications to maintain systolic blood pressure cap, and not demonstrate hemodynamic or respiratory concerns must be achieved and completed. We developed education for nurses and physicians in ED, ICU, and stepdown patient care areas and tip sheets to guide nursing care and documentation associated with the new protocol. Electronic orders were quickly developed and integrated as a new subphase specific to the Fast Track Alteplase Protocol within an existing stroke order set.

Results:
The protocol decreased the number of encounters between nursing and patients from 36 to 12 interactions (66.7%) and planned time in the ICU from 24 to 12 hours (50%). The median time comparison of ICU length of stay for Fast Track vs. traditional protocol was 12 hours and 26 min vs 35 hours and 15 minutes respectively.

Conclusion:
The protocol achieved both goals of decreasing the amount of time stroke patients are in the ICU and number of nursing encounters reducing the possibility of patient and staff exposure to COVID-19.
Abstract P825: Virtual Stroke Support Group: Innovative Approach to Continued Care in Times of Covid-19
Authors: Veenstra Adrienne , DuVerneay Jamie , Packard Laurel , Khan Muhib
Published: March 2021

Background and Purpose:
Post-stroke patients and their caregivers need continued physical and emotional support to adapt to the ‘new normal’. Stroke Support Groups are an effective educational platform for survivors and caregivers to discuss chronic post stroke issues. Stay at home orders and social distancing measures instituted to decrease the spread of COVID-19 made it difficult to conduct an in-person stroke support group. However, social isolation related to home quarantine would exacerbate the emotional toll associated with stroke. Therefore, we decided to proceed with a virtual stroke support group to provide continued education and emotional support to our stroke survivors and caregivers.

Methods:
Microsoft Teams Virtual Platform was utilized to conduct virtual stroke support group. Sessions were conducted once a month. Stroke Survivors and Caregivers were sent a link to their email to log into the virtual platform. The sessions were moderated by a recreational therapist and various speakers provided educational sessions.

Results:
Five virtual stroke support group sessions have been conducted. Topics discussed were COVID-19 check-in and discussion, Planning for an Uncertain Future, Brilliant Brain Party: Celebrating Neuroplasticity, Two Sides to Every Story: Left and Right Brain and How Humor Can Help Your Recovery. An average of 10 participants attend each of these sessions. Participants find these sessions valuable. It allows them to be part of the stroke community when they are unable to travel due to long distance, inclement weather and transportation availability. Challenges include lack of experience with technology, familiarity with conference call etiquettes and lack of visual cues related to emotional topics.

Conclusion:
Virtual Stroke Support Group is an innovative approach to keep stroke survivors and caregivers engaged in their care. We plan to have the option of virtual attendance available long term in addition to in-person attendance in the future.
Abstract P826: Does Telemedicine Impact Stroke Clinic Follow-Up During the Covid-19 Pandemic
Authors: Okpala Munachi N , Okpala Nnedinma , Cohen Audrey S , jaime frances , Trigazis Cynthia , HINOJOSA EVELYN , Monday Kimberly , Sharrief Anjail Z
Published: March 2021

Introduction:
The COVID-19 pandemic has led to rapid implementation of telemedicine (TM) care in outpatient neurology clinics. Early follow-up after acute stroke hospitalization has been associated with decreased readmission and improved care transitions. Stroke survivors may face multiple barriers to in-person follow-up, including inability to drive, limited mobility, and reliance on working caregivers; therefore TM may be preferred. We sought to evaluate the impact of TM care provision during the COVID-19 pandemic on patient follow-up.

Methods:
Using our clinic EMR, we included patients scheduled for stroke hospitalization follow-up in the Stroke Transitions, Education, and Prevention (STEP) clinic from 10/1/2019 till 7/31/2019. We calculated arrival rates, no-show rates, and cancellation rates for the pre-COVID time period (10/1/19 - 3/13/20) and the period following the implementation of TM services (3/17/20 - 7/31/20).

Results:
We identified 593 eligible patients with 282 patients scheduled in the pre-COVID period and 311 patients in the COVID period. Arrival, cancellation, and same day no-show rates were 63.1%, 23.0%, and 12.4% in the pre-COVID period and 54.0%, 37.9%, and 7.07% in the COVID period, respectively. The arrival rate decreased significantly (p=0.03) and the cancellation rate increased significantly (p<0.001); the same day no-show rate also decreased significantly (p=0.04).

Conclusion:
Despite the availability of TM services, the arrival rate for stroke patients scheduled for follow-up during the pandemic decreased significantly, largely because of cancellations. Low no-show rates do not explain the full picture of follow-up. Increased cancellations might be explained by several factors including barriers to technology, apprehension regarding TM, reliance on caregivers to participate in TM visits while practicing social distancing. Identification of barriers to TM follow-up should be further investigated to prevent the deleterious impact of poor care transitions on stroke patients.