bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract WP217: Increase Of Exosome Uptake By Activated Neurons In The Peri-infarct Region Improves Neurological Outcomes After Stroke
Authors: Zhang Yi , Zhang Li , Liu Zhongwu , Li Chao , Chopp Michael , Zhang Zheng Gang
Published: February 2023

Background:
We hypothesized that an increase of exosome uptake by activated neurons in the peri-infarct region enhances functional outcome. We tested this hypothesis by administering exosomes derived from cerebral endothelial cells (CEC-exos) to ischemic rats in conjunction with whisker stimulation.

Methods and Results:
Male adult rats were subjected to a transient right middle cerebral artery occlusion (tMCAO). Neuronal activation in the barrel cortex of the peri-infarct region after left whisker stimulation was confirmed by c-fos positive neurons. CEC-exos at a dose of 1x10^11 particles/injection were administered (i.v.) to tMCAO rats 15 min after whisker stimulation at every other day for 2 consecutive weeks, starting 1 day after tMCAO. Ischemic rats treated with CEC-exos alone or whisker stimulation alone significantly (p<0.05) improved sensorimotor functions (modified neurological severity scores, mNSS, 6±1 in CEC-exos or stimulation; foot-fault, FF, 11±1% in CEC-exos, 14±1% in stimulation) compared to ischemic rats treated with PBS (mNSS, 10±1; FF, 25±2%, n=7/group). However, combination of whisker stimulation with CEC-exos resulted in a super-additive (p<0.05) effect to improve sensorimotor functions (mNSS, 3±1, FF, 6±1%, p<0.05, n=7) compared to the monotherapies. Confocal microscopic analysis showed that stimulation significantly (p<0.05) increased neuronal uptake of CEC-exos (21±3 vs 3±1 exosomes/cell in CEC-exos alone, n=200 neurons/group), which was associated with significant (p<0.05) reduction of axonal inhibitory protein Sema6a in axons of activated neurons (relative levels 0.11±0.02 vs 0.31±0.07 in CEC-exos alone, n=3) . Increased neuronal uptake of CEC-exos was further confirmed at the ultra-structural level.

Conclusion:
Activated neurons in the peri-infarct areas preferentially increase uptake of CEC-exos, which contributes to significantly enhanced and robust improvement of neurological outcome during stroke recovery.
Abstract WP220: Platelet Inhibition Prevents Delayed Cerebral Ischemia After Subarachnoid Hemorrhage In Mice
Authors: Hong Sungha , Dienel Ari , Torres Kiara , Thomas Sithara , Thankamani Pandit Peeyush , Blackburn Spiros , McBride Devin
Published: February 2023

Subarachnoid hemorrhage (SAH) induces delayed cerebral ischemia (DCI) in about 30% of patients which is characterized by functional decline. As microthrombi is a cause of DCI, platelets may be a therapeutic target for preventing microthrombi formation and development of DCI. Clinical trials of anti-platelets have been inconclusive for their effect on outcome. However, clinical trials used different anti-platelets. Since platelets have numerous receptors which can each prevent thrombosis, there is no clear choice to target for SAH. Here, we utilize 6 platelet antagonists to identify if any receptor is a therapeutic target for DCI after SAH. Our hypothesis is that P2Y receptor inhibition will prevent microthrombi and reduce DCI after SAH. Male and female mice were randomly assigned into sham, SAH+vehicle, SAH+P2Y antagonism, SAH+PAR4 antagonism, SAH+PAF antagonism, SAH+TPβ-R antagonism, and SAH+GPIIb/IIIa antagonism. Mice were euthanized 2 (n=10/group) or 7 days (n=15/group) post-SAH. All outcomes were performed and data was analyzed by a blinded investigator. Behavior was assessed daily. Brain microthrombi were counted. Both male and female SAH mice treated with inhibitors of PAF and TPβ-R had significantly better day 1 function than vehicle-treated mice. Significantly better function on day 1 was also observed in only male mice treated the P2Y antagonists or GPIIb/IIIa antagonist. Neither sex had improved behavior for the PAR-4 inhibitor. Mice exhibiting better function had fewer brain microthrombi with the exception of the GPIIb/IIIa antagonist which reduced microthrombi in female mice but did not correspond with improved behavior. This suggests there may be another deleterious mechanism which is more prevalent/detrimental in females that is not prevented by GPIIb/IIIa inhibition, such as platelet degranulation. However, this needs to be further investigated. Additionally, inhibition of TPβ-R reduced the incidence of DCI compared to vehicle-treated mice. In conclusion, an anti-platelet drug for SAH needs to be chosen carefully as not all antagonists have a beneficial effect after SAH; of vital importance is that anti-platelet drugs may not have similar beneficial effects in both sexes.
Abstract WP222: Temporally Differentially Expressed MikroRNAs In Serum Predict Recovery In Different Acute Brain Injuries
Authors: Sajanti Antti , Hellström Santtu , Li Yan , Cao Ying , Girard Romuald , Frantzen Janek , Umemori Juzoh , Koskimaki Fredrika , Lyne Sean B. , Falter Johannes , Rantamäki Tomi , Nazir Kenneth , Gajera Bharat , Posti Jussi , Roine Susanna , Takala Riikka , Kolehmainen Sulo , Heino Iiro , Rahi Melissa , Rinne Jaakko , Nieminen Anni , Castren Eero , Koskimaki Janne
Published: February 2023

Background:
Brain plasticity is important processes in recovering after different types of acute brain injuries such as aneurysmal subarachnoid hemorrhage (aSAH), ischemic stroke (IS) and traumatic brain injury (TBI). Knowledge gaps still exist which miRNAs contribute to recovery of the acute brain injuries.

Hypotheses:
Temporally differentially expressed (DE) miRNAs after acute brain injuries may have association to outcome irrespective the type of the acute brain injury. MiRNAs that are DE across different type of brain injuries may reveal important conserved associations that can reflect important biological mechanisms and serve as a biomarker.

Methods:
Prospective cohort (n=24) consisted of IS (n=8), aSAH (n=8) and TBI (n=8) patients. Two serum samples were collected per patient (early 24-48h and late 120-192h after injury). Outcome was measured 90 days after injury (mRS favorable 0-3 (n=15), unfavorable 4-6 (n=9). MiRNAs were extracted from the samples (total n = 48 samples). Sequencing was performed and DESeq2 was used to identify DE miRNAs. The miRNA putative target genes were predicted with miRWalk. Normalized expression values of identified DE miRNAs were used and linear canonical discriminant analysis (LDA) was performed. Canonical scores were used to build combinatory biomarker with logistic modelling predicting outcome.

Results:
We identified 22 temporally DE miRNAs (p<0.05) that were in common across all acute brain injury types when compared between favorable and unfavorable groups. From this pool miRWalk target analysis identified 4 miRNAs (hsa-miR-146b-3p, hsa-miR-485-3p, hsa-miR-5010-5p, hsa-miR-485-5p) that targeted to known plasticity mechanism. LDA of these four miRNAs resulted an equation with canonical scores: 0.636 x [hsa-miR-146b-3p] + 0.576 x [hsa-miR-485-3p] + 0.652 x [hsa-miR-5010-5p] + 0.372 x [hsa-miR-485-5p]. The receiver operating characteristic curve generated showed AUC = 94.1%, 95% CI = (0.849, 1.00), p = 0.016

Conclusions:
Results show that combinatory biomarker of identified miRNAs perform well across different type of brain injuries. Validation in larger cohort is justified. Identified common miRNAs also provide new targets for mechanistical validation in disease models of TBI and stroke.
Abstract WP223: Identification Of Cerebral Amyloid Angiopathy With A Leukocyte Gene Expression Profile
Authors: Munsterman Danielle , Falcione Sarina , Long Rebecca , Joy Twinkle , Clarke Mike , Beaudin Andrew E , Camicioli Richard , Smith Eric E , Jickling Glen
Published: February 2023

Introduction:
Cerebral amyloid angiopathy (CAA) is a cerebral small vessel disease featuring beta-amyloid deposits within the cerebral vasculature. It is a major cause of cognitive decline and intracerebral hemorrhage in the elderly. This study evaluated whether gene expression profiles in peripheral blood can differentiate patients with CAA from vascular risk factor and healthy controls.

Methods:
In 27 patients with CAA blood cell gene expression was compared to 55 controls. Total RNA was isolated from PAXgene tubes and measured by RNA sequencing. Differentially expressed genes between CAA and controls were identified by ANOVA adjusting for age and sex. Functional pathway analysis identified pathways associated with CAA. A prediction model to distinguish CAA from controls was developed using linear discriminant analysis with feature selection by forward selection. Model performance was evaluated by 10-fold leave-one-out cross validation.

Results:
686 differentially expressed genes were identified (p<0.05, fold change >|1.2|), of interest
ADAM15, CAMK1D, CAP1
and
TGFB1
. Canonical pathway analysis identified cell movement of phagocytes, activation of phagocytes, CREB, degranulation of leukocytes, immune response of cells, inflammatory response, and IL-23 signaling. A 24 gene panel differentiated patients with CAA from controls with >95% sensitivity and specificity. The identified genes reveal differences in immune system regulation in patients with CAA compared to vascular risk factor and healthy control patients. Differences identified include a potential shift in beta-amyloid uptake by phagocytes (
TGFB1, CREB, CAMK1D
), an increase in vascular extracellular matrix disruption (
ADAM15, CAP1
), and a possible alteration in amyloid precursor processing (
BRI3BP, SORCS3
).

Conclusion:
Differences in peripheral leukocyte gene expression are present in patients with CAA compared to control patients. These relate to differences in immune activation and signaling associated with CAA. The differences in blood cell gene expression shows promise to distinguish CAA from controls, though further evaluation in larger cohorts is required to further evaluate potential diagnostic utility of this gene expression profile.
Abstract WP227: Endothelin Receptor A (eta) Inhibition By Intranasal Administration Of Bq-123 In Hypoperfused Diabetic Rats Exerts Different Effects In Various Domains Of Cognition
Authors: Abdul Yasir , JAMIL SARAH , Ergul Adviye
Published: February 2023

Cerebrovascular dysfunction leading to brain hypoperfusion is an early event in vascular cognitive impairment & dementia (
VCID
). Postmortem brain levels of endothelin (ET)-1, the most potent vasoconstrictor, closely correlate with blood barrier breakdown and hypoperfusion in individuals with VCID. The prevalence of diabetes in people with dementia is as high as 39%. We have reported that there is upregulation of circulating and brain ET-1 in diabetic male rats that later develop cognitive impairment and all the cell types of the neurovascular unit express ETA receptors. We hypothesized that inhibition of brain ETA receptors can prevent cognitive decline in diabetes.

Methods:
Experimental design is depicted in Fig 1. The impact of unilateral common carotid occlusion (UCCAO) on ETA receptor expression and brain hypoxia was assessed by immunohistochemistry. A battery of cognitive tests was performed.

Results:
Bioavailability of drug in brain post intranasal delivery was confirmed by LCMS. UCCAO increased the expression of HIF1a and ETA receptors in most of the cell types of NVU. Mobility of diabetic animals was significantly reduced (1522±272.8cm control vs 1051±61.17cm diabetic; p<0.05) without affecting the velocity. Other behavior outcomes are summarized in Fig 1.

Conclusions:
While hypoxic conditions increased the ETA receptor expression in the brain, in contrast to our hypothesis, ETA inhibition worsened recognition memory and promoted anxiety with no effect on short-term learning and spatial memory. The intranasal drug delivery approach may offer a novel approach to further investigate the complex role of the ET system without systemic side effects of ETA inhibition.
Abstract WP228: Stroke Risk Quantification For Patients With A Left Ventricular Assist Device
Authors: Sahni Akshita , McIntyre Erin E , Pal Jay D , Mukherjee Debanjan
Published: February 2023

Introduction:
Stroke is a leading cause of death and disability and a significant complication for heart failure patients on Left Ventricular Assist Device (LVAD) support. Most of these stroke cases are embolic in nature. Yet, specifics of embolus transport to the brain by the flow driven by an LVAD are poorly understood; precluding a clear understanding of post-implant stroke risks in these patients. Here we demonstrate an innovative stroke risk descriptor using in silico embolus transport analysis.

Methods:
Cardiac gated CTA images with LVAD graft were obtained for 6 patients. 3 patients reported post-LVAD stroke and the other 3 did not. 3D computer models of the LVAD graft, aortic arch, and branch vessels to the head were created using SimVascular. Blood flow from LVAD was computed for each model using LVAD flow rate and mean blood pressure as inputs. A custom fluid-particle interaction model for embolus transport was used to obtain the distribution of emboli entering the arch from the LVAD. A combination of normalized embolus distribution was used to create a stroke risk descriptor and compared across the stroke and non-stroke cases. Two sets of descriptors were defined using: (a) embolus distribution to the head; and (b) distribution to the head as well as accumulation at aortic root near the dysfunctional aortic valve.

Results:
We present results from 5,000 different embolism scenarios using representative thromboembolic particles of 1 mm diameter. For descriptor category (a) defined in Methods, the computed average for post-LVAD stroke cases was 0.35 as compared to 0.24 for those without post-LVAD stroke. For risk of embolic events in the brain including embolus accumulation in aortic root (i.e. descriptor category (b) in Methods) the reported averages were 0.38 and 0.27 for stroke vs no-stroke cases.

Conclusions:
The results indicate that our descriptor is a good surrogate for identifying stroke risks post-LVAD implantation, with stroke cases correlated with high values of the descriptor. The results also indicate that emboli traveling from LVAD graft into the arch, as well as emboli accumulating in regions of stasis at the aortic root may both contribute to stroke risks in patients with an LVAD. Continued investigations with bigger patient cohorts are needed.
Abstract WP23: Stroke Survivors Experience During The Covid-19 Pandemic: A Phenomenological Investigation
Authors: Kimmel Barbara , Anderson Jane , Walder Annette , Ovalle Anette , Venkatasubba Rao Chethan P
Published: February 2023

Background and Purpose:
Stroke occurs suddenly and can be a life-changing experience. Nearly 800,000 people in the United States each year suffer a stroke leading to major disability. Support of treatment of acute and follow-up care involves complex, evidence-based interventions to reduce death, stroke recurrence, post stroke disability and risk factors management. In 2019, American Heart Association released a policy guiding implementation of stroke systems of care. However, COVID-19 pandemic lockdowns changed public perceptions of when to seek stroke care. Little is known about care transformation due to pandemic. This study describes stroke survivors lived experience and challenges faced while seeking post-stroke care during pandemic across.

Methods and Analysis:
A qualitative phenomenological methodology was used to conduct the study. We enrolled 15 participants who had telemedicine follow-up visits and conducted in-depth interviews using study guide. Two independent reviewers used Giorgi descriptive method to search for essence of lived experience of surviving stroke and themes related to follow-up care using telemedicine.

Results:
Lived experience included variety of reactions due to an acute event such as life uncertainly, confusion and frustration, loneliness and worries. Unexpected challenges of care access and quality due to special COVID protocols and limited or no family support during hospital stay, emerged as additional themes. Themes related to follow-up care included post-stroke care coordination challenges, pros and cons of telemedicine encounters and practical aspects of using technology.

Conclusions:
Having a stroke during pandemic, created unexpected challenges that transformed post-stroke care. Individual approach was most important in dealing with challenges. Positive changes occurred while using telemedicine except in cases where full medical exam was needed. Patients recommended using hybrid approach for post-pandemic visits (in-person and telemedicine). Knowledge gained from this study can be used in a wider context of limitations imposed by other civilization-related epidemics.
Abstract WP234: Mitochondria Therapy Mitigates Neuroinflammation And Provides Neuroprotection Against Ischemic Stroke In Mice
Authors: Salman Mohd , Stayton Amanda S , Bajwa Amandeep , Ishrat Tauheed
Published: February 2023

Background:
Ischemic stroke is the second prevalent life-threat problem associated with long-lasting neurological disabilities and a high mortality rate worldwide. Despite this, therapeutic options remain limited. Recently, mitochondria transplantation therapy has emerged as a potential approach for increasing brain protection. This study aimed to investigate the protective role of mitochondria transplantation against ischemic stroke-induced behavioral deficits and molecular alterations in a photothrombotic stroke model.

Methods:
Ischemic stroke was induced by a Rose Bengal photothrombosis method in young adult C57BL/6 mice. Repeated doses of isolated liver mitochondria (100μg/mouse) were administrated intranasally at 1 h, 3 h, 24 h, and 48 h post-stroke. After 72 h, mice were tested for behavioral outcomes and euthanized, and tissues were harvested to measure infarct volume, brain edema, and molecular analysis.

Results:
Mitochondria-treated mice showed a significant improvement in behavioral outcomes, reduction in infarct size, and brain edema compared to the vehicle-treated group. Additionally, mitochondria significantly inhibited the protein expression of NOD-like receptor protein-3, phospho-nuclear factor kappa-B, cleaved-interleukin-1β, apoptosis-associated speck-like protein, glial fibrillary acidic protein, and ionized calcium-binding adapter molecule-1 proteins. Furthermore, mitochondria treatment showed a lower expression of nitrotyrosine, and 4-hydroxynonenal and higher expression of endothelial nitric oxide synthase and sulfotransferase-4A1 proteins, oxidative stress markers (
Table 1
).

Conclusion:
Taken together, these data indicate that mitochondria reveal neuroprotection through the attenuation of inflammation against stroke. Further investigations into the role of neuroprotection of mitochondria transplantation are needed to determine whether it can be an effective therapy for stroke patients.
Abstract WP237: Maternal Dietary Choline Deficiencies During Pregnancy And Lactation Reduce Cerebral Blood Flow In 3-month-old Female Mice Offspring Following Ischemic Stroke To The Sensorimotor Cortex
Authors: Jadavji Nafisa M , Pull Kasey , Folk Robert , Gusek Brikena , Esfandiarei Mitra
Published: February 2023

A maternal diet that provides adequate nutrition during pregnancy and lactation is vital to the neurodevelopment of offspring. One-carbon metabolism plays an important role in the closure of the neural tube of the developing embryo; however, the impact of maternal one-carbon dietary deficiencies on offspring neurological function later in life remains relatively unknown. Stroke is one of the leading causes of death globally, and its prevalence is expected to increase in younger age groups as the incidence of various risk factors for stroke increases. The aim of our study was to determine the impact of maternal nutritional deficiencies on cerebral flow and peripheral hemodynamics after ischemic stroke in adult offspring. Adult female C57BL/6J mice were placed on either control (CD), choline (ChDD) or folic acid (FADD) deficient diets for four weeks to deplete stores prior to mating and were maintained on the assigned diet during pregnancy and lactation. Female offspring were weaned on to a CD for the duration of the study. Ischemic stroke was induced in the sensorimotor cortex of 2- and 10-month-old female offspring using the photothrombosis model. Six weeks after induction of stroke, cerebral and peripheral blood flow was measured using the Vevo2100 Pulse Wave Doppler tracing modality. Three and half-month-old female offspring from a ChDD mothers had reduced blood flow in the posterior cerebral artery compared to CD mice, this effect disappeared in 11.5-month-old offspring. In 11.5-month-old females we observed changes in peripheral hemodynamics, but not in young animals. The findings of our study suggest that a maternal dietary deficiency in choline results in reduced blood flow in adult female offspring after ischemic stroke, but the long-term effects are not present. This result points to the key role of the maternal diet in early life neuro-programming, while emphasizing its effects on both fetal development and long-term cerebrovascular health.
Abstract WP239: Intestinal Alkaline Phosphatase: A Novel Regulator Of The Gut-brain Axis In Acute Ischemic Stroke
Authors: Macom Rhiannon , Lewellyn Kennedi , Tillema Abigail , Abdelgelil Betty , Rahimpour Shokofeh , Brown Candice
Published: February 2023

While strokes are typically associated with the brain, it is widely known that stroke outcomes are influenced by communication between the brain and peripheral organs. The gastrointestinal (GI) tract comprises a critical organ system that is affected during and after stroke, and the interaction between the GI tract and the brain in stroke is attributed to the modulation of the gut-brain axis. Intestinal alkaline phosphatase (IAP; gene:
Akp3
) is a brush border enzyme localized in the intestinal epithelium that regulates intestinal homeostasis by modulating inflammation and intestinal integrity. We hypothesized that IAP regulates the early post-stroke changes within the gut-brain axis, and that loss of IAP disrupts the gut-brain axis to worsen post-stroke outcomes and disrupt immune responses. We utilized 4-6 month-old male and female mice with a genomic deletion of
Akp3
and their wild type (WT) littermate controls. Following the induction of photothrombotic stroke (PTS), stroke-injured mice and their sham controls were for evaluated for bacterial load, intestinal permeability, intestinal motility, neurological deficits, cerebral blood flow, and immune responses over the next 24 hours. Statistical analysis of Clark’s neurological score, laser speckle flowmetry, and 2,3,5-Triphenyltetrazolium chloride (TTC) staining at day 1 post stroke showed a main effect of stroke but no differences between genotypes. While no differences in intestinal motility were observed due to stroke or genotype, gut permeability to 3kD-FITC dextran quantified at 3.5 hours post-stroke was higher in
Akp3-/-
mice compared to WT mice. Further analysis of bacterial burden showed that anaerobic bacteria in the ileum were diminished in
Akp3-/-
mice post-stroke compared to WT counterparts. Quantification of immune cell populations in cervical lymph nodes and spleen showed that
Akp3-/-
mice displayed baseline decreases in monocyte and dendritic cell populations that were either maintained or further decreased at 24-hours post-stroke, suggesting that Akp3-/- mice are unable to mount an appropriate innate immune response in acute stroke. Taken together, the current results support the hypothesis that IAP shapes early outcomes and modulates the gut-brain axis in ischemic stroke.
Abstract WP240: TRPM2 Channel Deletion In Neurons Reduces Injury Following Ischemic Stroke And Improves Post-stroke Cognitive Function
Authors: Coakley Kelley A , Orfila James E , Apolinario Tiria D , Loehfelm Alexis M , Herson Paco S
Published: February 2023

Background:
Emerging evidence implicates post-stroke cognitive impairment as a major contributor to long-term disability. Therefore, optimal therapeutic targets reduce acute ischemic injury and enhance post-stroke brain function. Strong data demonstrates that a novel TRPM2 channel antagonist (tat-M2NX) provides neuroprotection and improves synaptic function, thereby reducing post-stroke cognitive impairment (PSCI).

Hypothesis:
Knockout of neuron-specific TRPM2 channel expression reduces infarct volume and enhances functional recovery following MCAO

Methods:
Transient MCAO (60 min) was performed on adult (8-10 week) male and female TRPM2 neuron-specific KO (TRPM2fl/fl, CaMKII Cre) and TRPM2 floxed controls (TRPM2fl/fl)Hemispheric infarct volume analyzed from MRI (T2) images 3 days post-injury by a blinded investigator. Extracellular field recordings of CA1 neurons were performed in acute hippocampal slices prepared 7 days after recovery from MCAO to analyze synaptic placticity (LTP).

Results:
We observed that neuronal-specific TRPM2 channel knockout reduces acute ischemic injury (infarct volume) in male animals, while having minimal effect on female mice. Consistent with the hypothesis that neuronal TRPM2 channels contribute to ischemia-induced synaptic dysfunction, recordings obtained in brain slices from neuronal TRPM2 channel KO mice (TRPM2fl/fl-CaMKII CRE) mice 7 days after recovery from 60 min MCAo exhibited intact hippocampal plasticity compared to control TRPM2fl/fl mice not expressing CRE. Male sham control mice exhibit robust LTP of 163±10.4% (n=3) compared to 115±5.6% (n=4) in TRPM2fl/fl mice after MCAO. Neuronal KO exhibited 175±9.8% (n=2). Similarly, female mice had control LTP of 170±6.8% (n=4) compared to 125±6.8% (n=3) in TRPM2fl/fl mice after MCAO. Neuronal KO exhibited 208±7.8% (n=5, p<0.05 ANOVA compared to TRPM2fl/fl MCAO).

Conclusion:
Our data highlight that TRPM2 channels expressed in neurons contribute to both acute injury following transient ischemic stroke and subacute/chronic functional recovery.
Abstract WP243: Csf1r Antagonism Abolishes Ischemic Preconditioning Mediated Protection In White Matter
Authors: Hamner Margaret , McDonough Ashley , Nielson Cara , Gong Davin , Todd Levi , Rojas German , Reh Thomas , Ransom Bruce R , Weinstein Jonathan R
Published: February 2023

Background:
Ischemic preconditioning (IPC) is a robust protective phenomenon whereby brief ischemic exposure confers protection against a subsequent prolonged ischemic challenge. IPC has been studied primarily in gray matter predominant models, however, stroke significantly impacts white matter (WM). We have previously reported development of a WM IPC model in the mouse optic nerve (MON), a fully myelinated CNS WM tract. We identified innate immune signaling pathways as required for axonal protection, however the cell type(s) responsible for IPC in WM are unknown. Here we characterize the effects of microglial depletion on IPC-induced protection against OGD-mediated injury to: (i) axonal compound action potential (CAP) recovery, (ii) axonal structural integrity, (iii) oligodendrocyte viability and (iv) nodes of Ranvier (NoR) in MON.

Methods:
Following microglial depletion by pharmacologic treatment with colony stimulating factor 1 receptor (CSF1R) inhibitor PLX5622, MONs were exposed to transient ischemia in vivo, acutely isolated, and subjected to oxygen-glucose deprivation (OGD) ex vivo to simulate a severe ischemic injury. Functional and structural axonal recovery was assessed by electrophysiology with recording of CAP and immunofluorescent/confocal microscopy followed by quantitative stereology.

Results:
Microglial depletion eliminated IPC-mediated protection of axonal function but intriguingly had no effect on recovery after acute ischemic injury alone (i.e. in the absence of IPC). Microglial depletion abrogated IPC-mediated protective effects on both axonal integrity and the survival of mature (APC+) oligodendrocytes after exposure to OGD. IPC-mediated protection was determined to be independent of retinal injury. Effects on NoR remain under investigation.

Conclusions:
Based on these findings, we conclude that preconditioned, but not naïve, microglia are critical in the endogenous IPC-induced protective response against ischemic injury that occurs in WM. Thus, preconditioned microglia are a critical cellular target for future therapeutics designed to enhance WM recovery from acute ischemic injury (stroke). Furthermore, our data suggest that IPC-mediated protection in WM is anatomically intrinsic to WM.
Abstract WP246: Ischemic Outcome In Young And Adult Offspring After Maternal Dietary Deficiencies In One-carbon Metabolites During Pregnancy And Lactation
Authors: Jadavji Nafisa M , Clementson McCoy , Hurley Lauren , Jauhal Jesse , Coonrod Sarah , Bennett Calli , Pull Kasey , Pascual Agnes , Wasek Brandi , Bottiglieri Teodoro , Malysheva Olga , Caudill Marie
Published: February 2023

Maternal one-carbon metabolism, including dietary levels of folic acid and choline, play an important role in early life programming. There is a well-established connection between the fetal environment and the health status of offspring. However, there is a gap in knowledge on how maternal nutrition will affect the health status of the offspring after a cardiovascular event like ischemic stroke. The aim of our study was to investigate the role of maternal dietary deficiencies in folic acid or choline on stroke outcome in 3- and 10-month-old male and female offspring. Adult female mice were fed a folic acid deficient diet (FADD), a choline deficient diet (ChDD), or a control diet (CD) four weeks prior to pregnancy to deplete stores, they were continued on diets during pregnancy and lactation. Male and female offspring were weaned onto a control diet and at 2 or 10 months of age were subject to ischemic stroke within the sensorimotor cortex via the photothrombosis ischemic damage model. At 3 or 11 months of age, motor function was measured in offspring and tissue was collected for analysis. Mothers maintained on either a FADD or ChDD had reduced levels of
S
-adenosylmethionine in liver tissue compared to controls. In offspring after ischemic stroke, motor function was impaired in 3-month-old male and female offspring from deficient mothers compared to control diet offspring. In 11-month-old mice there was no impact of maternal diet on motor function, but we observed sex differences. Male middle-aged adult mice had worse motor function compared to female offspring. In brain tissue, there was no impact of maternal diet on ischemic damage volume in 3-month-old animals. Interestingly, maternal diet impacted ischemic damage in 10-month-old male and female offspring. Neurodegeneration and choline metabolism in ischemic brain tissue was also impacted in 3 and 11-month-old offspring. The findings of our study suggest that a maternal diet deficient in either choline or folic acid impacts stroke outcome in young animals compared to middle-aged animals. These results points to the important role of the maternal diet in early life programming, while emphasizing its effects on both fetal development and long-term cerebrovascular health.
Abstract WP28: Closing The Revolving Door: Reducing Stroke Readmissions
Authors: Robertson Betty , Steiner Nili , Wolber Nicole , Izzo Rachel , Castro Marissa , Figueroa Sonia , Paletz Laurie B
Published: February 2023

Stroke is a leading cause of long-term disability where its impact and consequences can be pervasive. Although stroke management has evolved over the years, post stroke complications can lead to readmissions. It is estimated that approximately 90% of readmissions are unplanned resulting in an annual cost of $17.4 billion.The Centers for Medicare and Medicaid Services (CMS) in the attempt to limit preventable readmissions has adjusted hospital reimbursement based on these rates to establish accountability. As a Comprehensive Stroke Center, we instituted benchmarks in the attempt to decrease our re-admission rates. We recognize that the transition from in patient to outpatient services can create a vulnerable period that increases the risk for readmissions.

Smart aim:
To decrease 30-day readmission rates in the Stroke population at Cedars Sinai Medical Center

Implementation process:
We provided an inpatient pharmacist to implement stroke prevention medication education with an addition follow up phone call to address questions and confirm compliance. Secondly ensuring personalized Stroke education to patient and the families allowing assessment of needs prior to discharge. Thirdly calling our patients 7 days from discharge identifying if follow up appointments were made, prescription being taken and status in recovery.

Results:
From July 2020 to June 2021 the readmission rate was 9.5 %. Starting July 2021 to March 2022 we implemented the above modalities. This resulted in a decreased rate of 6.8% for this period.

Conclusion:
All the measures implemented made a significant improvement in the 30-day unplanned readmission rate for stroke patients. We recognized that inpatient and outpatient medication reconciliation provided one of the most significant factors that improved these rates. Proper medication education for patients and families improved adherence and in turn aids in secondary stroke prevention. Since this measure shows significant improvement, tracking and reviewing 90-day readmissions going forward seems prudent. Recognizing risk during this period allows the healthcare worker to intervene in anticipation of patients’ needs allowing for better patient outcomes and satisfaction as well as lessen the economic toll of care.
Abstract WP33: Bedside Insertion Of Implantable Loop Recorders Prior To Hospital Discharge Improves Detection Of Atrial Fibrillation After Cryptogenic Stroke And May Reduce Stroke Recurrence
Authors: Johnson Jennifer R , Georgiana Larry
Published: February 2023

Atrial fibrillation (AF) is responsible for 15-20% of ischemic strokes. AF can be asymptomatic and remain undetected following acute stroke, initially classifying the event as cryptogenic. Implantable loop recorders (ILRs) provide long-term cardiac monitoring and are superior to traditional methods for detecting AF in patients with cryptogenic stroke. ILR placement is often performed by a cardiologist in an outpatient setting. Our institution identified that some patients were missing or cancelling appointments for device implantation. Failure to detect AF is associated with a greater risk of stroke recurrence. An interdisciplinary inpatient process was developed to place ILRs at the bedside on the stroke unit, prior to discharge. The purpose of the program was to increase patient compliance with ILRs, improve detection of asymptomatic AF, and reduce incidence of stroke recurrence through timely initiation of oral anticoagulants. To evaluate the program and provide recommendations, measures of success included rates of patient compliance with ILR implantation using inpatient vs. outpatient procedure and the percentage of patients who received a diagnosis of AF after ILR placement. Using 18 months of pre-implementation data as a benchmark, the average implant rate increased in the first 12 months following implementation. Of 97 patients who received ILR placement, nine (9%) have received a diagnosis of AF. Since three-year ILR monitoring has shown significantly higher AF detection than 30-day cardiac monitoring after cryptogenic stroke, more patients with AF may yet be identified. This presentation will demonstrate an increase in ILR implant rates and AF detection and highlight positive results using advanced practice professionals to perform the procedure. The program produced financial benefit and mitigated access to care barriers, with no poor outcomes or compromise in quality, and no negative impact on inpatient length of stay. In conclusion, bedside insertion of ILRs prior to discharge after cryptogenic stroke is a safe, efficient, cost-effective process that increases patient compliance when compared to outpatient return visits, improving detection of AF and prompt initiation of oral anticoagulants, and may reduce stroke recurrence.
Abstract WP37: Prehospital Stroke Scales Outperform National Institutes Of Health Stroke Scale In Predicting Large Vessel Occlusion In A Large Telestroke Network
Authors: English Stephen W , Chhabra Nikita , Hanus Abigail , Basharath Rida , Miller Monet , Butterfield Richard , Zhang Nan , Demaerschalk Bart M
Published: February 2023

Introduction:
Prehospital telestroke is increasingly utilized in mobile stroke units and telemedicine-enabled ambulances for acute ischemic stroke (AIS). While the NIHSS remains the standard for telestroke assessment, simpler scales have been validated to help paramedics recognize large vessel occlusion (LVO) strokes but have not been evaluated in a traditional telestroke network. We aimed to determine the accuracy of common LVO scales in a large academic telestroke practice.

Methods:
This retrospective study included all telestroke consults performed in a large academic telestroke network from 2019 to 2020. Patients were excluded if no NIHSS or vessel imaging was performed. We recorded presenting NIHSS, site of vessel occlusion, and discharge diagnosis. LVO was defined as an acute occlusion of the internal carotid artery and/or M1 middle cerebral artery. The NIHSS was used to calculate 7 LVO scales (RACE, C-STAT, FAST-ED, 3I-SS, PASS, VAN, and G-FAST). Diagnostic performance was assessed by calculating sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV), and accuracy using the established thresholds of each scale. These results were compared to NIHSS at thresholds of 6, 8, and 10. Area under curve (AUC) was calculated using c-statistics by treating scales as continuous variables.

Results:
A total of 625 patients were included, 373/625 (59.7%) of which were diagnosed with AIS at discharge. LVO was identified in 78/625 (12.5%) patients. VAN was the most sensitive prehospital stroke scale (83.3%), whereas 3I-SS ≥ 4 was the most specific (95.2%). Both the RACE and FAST-ED scales demonstrated superior accuracy and AUC compared to the NIHSS (Table 1).

Conclusions:
To our knowledge, this is the first study assessing LVO scale accuracy in a large telestroke network. As use of prehospital telestroke grows, this study highlights several scales that may allow for faster prehospital triage decisions without sacrificing accuracy.
Abstract WP42: Real-world Utilization Of Advanced Imaging Based Patient Selection For Thrombectomy
Authors: Sevilis Theresa , Fowler Mariecken , Avila Amanda , Boyd Caitlyn , Gao Lan , Heath Gregory W , Ayub Hira , Devlin Thomas
Published: February 2023

Introduction:
Multiple clinical trials support an extended treatment window for thrombectomy for large vessel occlusions (LVO) and the treatment of distal occlusions, leading to increased numbers of patients requiring advanced imaging during acute stroke evaluation. Across hospital systems, there is great variation in advanced imaging protocols for acute stroke patients. The goal of this study is to provide a descriptive analysis of the real-world practices in facilities across the United States.

Methods:
Acute stroke consultations seen by TeleSpecialists, LLC physicians in the emergency department in 227 facilities (27 states) from July 1, 2021 to December 31, 2021 were extracted from the TeleCare
TM
database. The encounters were reviewed for age, ethnicity, stroke risk factors, last known normal (LKN), arrival time, thrombolytics candidate, door to needle (DTN) time, advanced imaging, LVO, if Neurointerventionalist (NIR) accepted case, premorbid modified Rankin Score (p-mRS), and NIHSS score. Comparison of baseline characteristics and time benchmarks between advanced imaging group (computed tomography angiography (CTA) with optional CT perfusion (CTP)) vs no advanced imaging group (CT only) was performed. Analysis of the location of the occlusion and of the specific vessels being accepted for intervention was performed.

Results:
There were 29,187 acute stroke consultations seen with 12,641 (43.3%) receiving advanced imaging. The median DTN time for advanced imaging group was 44 minutes (33, 59) vs 41 minutes (30.5, 54) with no advanced imaging group, p = 0.158. There was a higher NIHSS score and lower p-mRS in the advanced imaging group. Analysis of patients with LVO showed lower DTN times, higher NIHSS scores, lower p-mRS, and shorter LKN to arrival times in the patients accepted for thrombectomy. Majority of cases accepted for thrombectomy were left M1 (31.4%) or right M1 (26.6%) occlusions. A significantly lower percentage of patients accepted for intervention had left M2 (10%) and right M2 (6%) occlusions.

Conclusion:
Advanced imaging in a large real-world data set of acute stroke patients did not significantly delay DTN times. The ability to maintain DTN times is likely related to thrombolytics being prioritized and a parallel process.
Abstract WP43: Characteristics And Management Of Hospitalized Retinal Artery Occlusion Patients In The Era Of Updated Guidelines: A Population-based Study
Authors: LaPorta Joseph C , Robinson David , Stanton Robert J , Kleindorfer Dawn O , Ferioli Simona , Aziz Yasmin , Sucharew Heidi , Haverbusch Mary , Kissela Brett M
Published: February 2023

Background:
Retinal artery occlusion (RAO) is a stroke equivalent that causes significant morbidity. There has been growing emphasis on urgent in-hospital evaluation of these patients, both to facilitate potential thrombolytic therapy and expedite workup; however, little is known regarding its effect on systems of care. We thus examined presenting characteristics and management of hospitalized RAO patients using the Greater Cincinnati Northern Kentucky Stroke Study (GCNKSS).

Methods:
The GCNKSS is a population-based study of stroke in a 5-county region with a population of 1.3 million representative of the USA in terms of Black race, income, and education. All cases of RAO among Black individuals from July 2019-December 2020 and among White individuals from 2020 were chart abstracted using ICD codes. All cases underwent physician adjudication. Demographic and clinical data were recorded.

Results:
We identified 57 hospitalizations with acute RAO among 55 patients. Characteristics of their hospitalization and demographics are shown (Table). Notably, 19% (11/57) of patients presented in a thrombolytic window of ≤3.5 and average time from symptom onset to evaluation was 17 hours. Most patients initially interacted with a subspecialist (53%) and presented to the ED in delayed fashion. One patient received thrombolytic therapy, four (7%) patients underwent carotid revascularization, and no patients had newly identified atrial fibrillation, cardiac thrombus, or endocarditis.

Discussion:
Our population-based study found only a minority of patients presented within a thrombolytic window, suggesting that systems of care need to promote more rapid evaluation of these patients. Very few patients received select intervention, but the high impact of carotid revascularization may warrant urgent evaluation of even low risk patients. Further study of long-term outcomes in this patient population is called for.
Abstract WP44: Long Functional Outcomes After Acute Stroke Treatment After Implementation Of Mobile Stroke Unit Program
Authors: Khan Arham A , Ferra Katherine , Reinsel Ruth , Fiorella David , Mathew Jason
Published: February 2023

Background:
Mobile stroke units (MSU) were developed as a tool to facilitate rapid delivery of acute stroke treatments and improving patient functional outcomes. Currently, there is limited data on the functional outcomes of patients receiving acute stroke treatments after being transported by MSU. In 2019, Stony Brook University Hospital (SBUH) implemented 2 mobile stroke units to assist with rapid delivery of acute stroke treatments. We sought to compare the long-term functional outcomes of patients who received acute stroke treatment after transport by our MSU versus conventional transportation prior to MSU implementation.

Methods:
This is a retrospective study of patients who received either tissue plasminogen activator (t-PA) and/or thrombectomy between the years 2017-2020 (n=316). Patients were separated into two groups; Either receiving care via MSU to SBUH (n=107) or receiving care after arrival/transfer to SBUH via conventional transportation (n=165). Time interval from door to t-PA administration and door to groin puncture were measured. T test for independent samples were used to measure differences in time among both groups. Long term functional outcomes were measured using modified Rankin Scale (mRS) at 90 days. Patients were trichotomized into three outcome groups, mRS 0-1, 2-4, and 5-6. Chi square was used to analyze differences among the outcome groups.

Results:
The MSU patients had a significantly shorter Door to TPA time than the control group: (28 min±22 min vs. 63 min ±40 min respectively, t=4.770, 74 df, P<0.001). MSU patients had significantly shorter Door to groin puncture time than the control group (69 min ± 57 min vs 155min ± 271 min. respectively, t=2.807, 234 df, P<0.001). In MSU group (44), 41% had favorable mRS 0-1 compared to control group 23% (31) with mRS of 0-1. MSU group had 36% (44) moderate mRS 2-4 compared to control group 45% (31) with mRS of 2-4. MSU group had 23% (41) severe mRS 5-6 compared to control group 33% (31). X
2
=9.770, 2df, p <.01

Conclusions:
MSU transported patients had shorter door to t-PA and thrombectomy times compared to patients using traditional EMS transfer system in Suffolk County. This improvement translated into more favorable long-term patient outcomes as seen with more MSU patients with lower 90 day mRS.
Abstract WP47: Telemedicine And Remote Research Practice Use In Clinical Trials Among StrokeNet Sites
Authors: Staugaitis Abbey , Ramezani Solmaz , Frasure Jamey , Khatri Pooja , Broderick Joseph P
Published: February 2023

Background:
A hybrid of remote and in-person conduct of research may improve recruitment and retention rates in clinical trials. However, little is known about the current state of remote research practices (RRPs) in stroke trials. Our objective was to characterize the use of telemedicine and RRPs among sites, including Regional Coordinating Centers (RCCs), within NIH StrokeNet.

Methods:
All NIH StrokeNet clinical sites were sent a standardized questionnaire surveying their voluntary adoption of telemedicine and RRPs in stroke clinical trial recruitment both locally and remotely at affiliated stroke hospitals. The survey was distributed to attendees of the spring StrokeNet conference. The survey results are described using descriptive statistics.

Results:
Overall, 39 StrokeNet sites (16 RCCs [64.0%]) responded to the survey between April 2022 and July 2022. Thirty-one sites (79.5%) used telemedicine in clinical trials in the following settings: outpatient (66.7%), Emergency Department (46.2%), and inpatient (41.0%). Telemedicine was most commonly utilized for follow-up assessment (51.3%), trial screening (43.6%), obtaining informed consent (43.6%), and guiding the study intervention (33.3%). Reported rates of electronic informed consent use was as follows: 30 sites (76.9%) for acute stroke trials, 22 (56.4%) for secondary stroke prevention trials, and 15 (38.4%) for stroke recovery trials. Only 9 sites (23.1%) reported remotely enrolling patients at affiliated telestroke hospitals and 8 sites (20.5%) initiated study interventions remotely.

Conclusions:
Telemedicine and e-consent were used at many responding StrokeNet clinical trial sites. Future research is needed to understand the added value of telemedicine and RRPs in clinical research, barriers to adoption, and ideal future state.