bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 19: Long-lasting Post-stroke Memory Dysfunction In Aged Mice Is Like Due To Exacerbated Hippocampal Inflammation And Synapses Removing
Authors: Pan Peipei , Li Qifeng , Wang Zhanqiang , Liang Rich , Huo Kang , Ding Eric , Beon Chandler , Press Kelly , Su Hua
Published: February 2022

Background and Purpose:
Stroke can cause memory dysfunction. Long-term memory dysfunction of mice with tibia fracture (BF)+stroke is associated with accumulation of CD68
+
cells in the hippocampus, which can be alleviated by activation of alpha-7 nicotinic acetylcholine receptor (α-7 nAchR). Microglia maintain normal memory via removing excessive synapses. We hypothesize that aged mice would develop long-lasting memory dysfunction after stroke, which is associated with increased CD68
+
cells and synapses removing in the hippocampi.

Methods:
Permanent distal middle cerebral artery occlusion (pMCAO) was performed in young (2-month-old) and aging (15-18-month-old) mice, or 6 hours before pMCAO in young mice. The memory functions were analyzed weekly for 8 weeks by Y-maze and at 8 weeks post pMCAO by NOR tests. Atrophic volumes, CD68
+
cells and microglial phagocytosis of synapses were quantified at 8 weeks after pMCAO.

Results:
Aged mice had larger atrophic volumes, more CD68
+
cells in the hippocampi ipsilateral to stroke side than young mice, and also had more CD68
+
cells in the ipsilateral hippocampus than the contralateral. In Y-maze test, the aged stroke mice made fewer spontaneous alternations from 3 to 8 weeks after pMCAO than the young stroke mice and sham aged mice. In NOR test, aged stroke mice spent less time on the novel object than young stroke mice and sham aged mice. α-7 nAchR agonist treatment reduced the number of CD68
+
cells in the hippocampi in the BF+stroke mice. Almost all CD68
+
cells were synaptophysin positive. Therefore, increased CD68
+
cells in the ipsilateral hippocampus will increase synaptic removal. Reduction of neuroinflammation could reduce synaptic loss and improve post-stroke memory function.

Conclusions:
Increased CD68
+
cells in the hippocampus is associated with long-lasting post-stroke memory dysfunction in aged mice, and reduced neuroinflammation could improve post-stroke memory function.
Abstract 20: Targeted Ablation Of STAT1 Enhances Resolution Of Inflammation By Microglia/macrophages And Promotes Long-term Recovery After Ischemic Stroke
Authors: Shi Yejie , Li Sicheng , Pu Hongjian , Liu Yaan , Wang Rongrong , Ye Qing , Stetler Ruth A
Published: February 2022

Introduction:
Identification of key molecules that control conversion of resting microglia/macrophages (Mi/MΦ) to a detrimental or beneficial phenotype may help develop novel therapies to ischemic stroke. The transcription factor STAT1 contributes to acute (< 24h) neuronal death after brain ischemia/reperfusion (I/R), but its role in Mi/MΦ and impact on long term stroke outcome remain unknown.

Hypothesis:
Activation of STAT1 dictates proinflammatory responses of Mi/MΦ at subacute stage (3-5 d) after I/R. Selective deletion of STAT1 reprograms Mi/MΦ into an inflammation-resolving phenotype and improves long term stroke outcome.

Methods:
We generated mice with tamoxifen-induced, Mi/MΦ-specific knockout (mKO) of STAT1. Brain injury, inflammation and various behavioral deficits were assessed after 1 h MCAO and 1-35 d reperfusion. Mi/MΦ phenotype was examined
in vivo
(FACS followed by RNA-seq) and
in vitro
(primary microglia).

Results:
STAT1 was activated (phosphorylated) in Mi/MΦ 3 d after I/R in WT but not in STAT1 mKO mice. STAT1 mKO did not alter 24-h infarct size (TTC; p>0.05, n=8), but attenuated Mi/MΦ release of HMGB1 and increased arginase 1-producing Mi/MΦ 3d after I/R (immunostain, n=6), suggesting boosted inflammation-resolving responses of Mi/MΦ. RNA-seq further revealed downregulated proinflammatory genes and a concomitant elevation of phagocytosis-related genes in STAT1 mKO Mi/MΦ 3d after I/R (n=3, FDR<0.05). Consistently, phagocytosis of dead neurons was enhanced in STAT1 mKO mice 3d after I/R (n=7) or in cultured STAT1 KO microglia (n=4). As a result, STAT1 mKO mitigated brain inflammation 5d after I/R (ELISArray; 11 out of 27 markers, p<0.05, n=6), and improved motor/cognitive functions for 35d in mice of both sexes (p<0.01 vs WT, n=10-11).

Conclusions:
Mi/MΦ-targeted STAT1 KO does not offer acute neuroprotection but primes Mi/MΦ toward an inflammation-resolving phenotype, thereby facilitating long term functional recovery after stroke.
Abstract 21: Genetic Deletion Of MicroRNA-15a/16-1 In Pericytes Stimulates Cerebral Angiogenesis And Promotes Long-term Functional Recovery After Ischemic Stroke
Authors: Sun Ping , Xu Yang , Zhou Chao , Yin Kejie
Published: February 2022

Introduction:
Post-stroke cerebral angiogenesis actively participates in tissue repair and plays a vital role in the long-term functional recovery in stroke patients. Accumulating evidence shows that certain microRNAs (miRs) regulate cerebral angiogenesis after CNS disorders. We have demonstrated that endothelium-targeted deletion of miR-15a/16-1 promotes post-stroke angiogenesis by enhancing activity of pro-angiogenic factors and their receptors. Here we further investigate the effects of pericyte-derived miR-15a/16-1 on post-ischemic cerebral angiogenesis and outcomes.

Methods:
Inducible pericyte-specific miR-15a/16-1 cKO mice and WT littermate controls were subjected to 1h MCAO and 28d reperfusion. Neurobehavioral outcomes were determined by the foot fault, rotarod, adhesive tape removal, and Morris water maze tests. Brain atrophy was measured by MAP2 immunostaining. Cerebral blood flow (CBF) was monitored by laser speckle imaging. Brain capillary density, functional microvessels, and neurons were examined by CD31/BrdU, tomato lectin/BrdU, and NeuN/BrdU double immunostaining, respectively.
In vitro
angiogenesis assays, including BrdU cell proliferation, scratch assay, and capillary tube formation were analyzed in mBMEC cutures treated with conditional medium from primary mouse vascular pericytes (mBVPs) with lentivirus-mediated miR-15a/16-1 knockdown. Pro-angiogenic factors were detected by qPCR and western blotting.

Results:
Pericytes-miR-15a/16-1 cKO mice exhibit improved sensorimotor and cognitive outcomes, increased CBF recovery, and reduced brain atrophy compared to WT controls. The number of newly-generated cerebral microvessels, functional microvessels, and neurons in the peri-infarct brain regions of Pericyte-miR-15a/16-1 cKO mice are higher than WT controls. Treatment of conditional medium from miR-15a/16-1 silencing pericytes significantly increases endothelial cell proliferation, migration, and tube formation, respectively. Mechanistically, lentiviral silencing of miR-15a/16-1 in primary mBVPs remarkably enhances the expression of both FGF2 and VEGFA.

Conclusions:
Our findings suggest that pericytic miR-15a/16-1 negatively regulates post-stroke cerebral angiogenesis.
Abstract 26: Timing The Optimal Transfer Modality For Suspected Large-vessel Stroke Patients: A Post-hoc Analysis Of The Racecat Trial
Authors: Garcia-tornel Garcia Alvaro , Rubiera Marta , Olive-gadea Marta , Requena Manuel , boned sandra , Muchada Marian , Pagola Jorge , Rodriguez-luna David , deck matias , Juega Jesus M , Rodriguez-Villatoro Noelia , tomasello alejandro , Piñana Carlos , Hernandez David , Purroy Francisco , Perez de la Ossa Natalia , Abilleira Sonia , Molina Carlos A , Ribo Marc
Published: February 2022

Introduction:
Current recommendations for regional stroke destination suggest that patients with an acute severe stroke should be triaged based on estimated time to arrival to a thrombectomy-capable center. We aimed to evaluate which time period available at the time that patient is triaged is able to discriminate which transfer modality should be chosen.

Methods:
We built and ordered logistic regression model adjusted for multiple comparisons with the RACECAT trial population using time periods available during triage: time from onset to emergency medical services (EMS) evaluation, estimated time of arrival to the thrombectomy-capable center and between centers distance. Estimated times were computed using a distance matrix API. Primary outcome was disability at 90 days, as assessed by the shift analysis on the modified Rankin score.

Results:
Of the 1369 patients evaluated, median time from onset to EMS evaluation, estimated time to arrival to the thrombectomy-capable center and between centers distances were 65 minutes (interquartile ratio (IQR) 43 to 138), 61 minutes (IQR 36 to 80) and 62 minutes (IQR 36 to 73), respectively. In patients transferred to local stroke centers, delay in EMS evaluation was associated with higher degrees of disability (for each 30 minutes delay, adjusted common odds ratio (acOR) 1.035, 97.5% confidence interval (CI) 1.005 to 1.066), with no influence in patients directly transferred to thrombectomy-capable centers (for each 30 minutes delay, acOR 0.999, 97.5% CI 0.981 to 1.018) (p
interaction
=0.048). In patients evaluated by EMS above 120 minutes after stroke onset, direct transfer to a thrombectomy-capable center was associated with lower degrees of disability (acOR 1.494, 95% CI 1.026 to 2.174).

Conclusion:
In the RACECAT trial, delay in EMS evaluation was associated with higher degrees of disability in patients transferred to local stroke centers and may serve as a potential biomarker for prehospital triage optimization.
Abstract 38: Magnitude Of Blood Pressure Change After Endovascular Therapy And Outcomes: Insight From Bp Target Trial
Authors: Anadani Mohammad , Maier Benjamin , Escalard Simon , Labreuche Julien , de Havenon Adam H , Sabben Candice , LAPERGUE Bertrand , Gory Benjamin , Richard Sebastie , Sibon Igor , Desilles Jean-philippe , BLANC RAPHAEL , Piotin Michel , Mazighi Mikael ,   BP TARGET
Published: February 2022

Background:
To assess the association between systolic blood pressure change (ΔSBP) at different time intervals after successful reperfusion with radiographic and clinical outcomes.

Methods:
This is a post hoc analysis of the Safety and efficacy of intensive blood pressure lowering after successful endovascular therapy in acute ischaemic stroke (BP TARGET) multicenter trial. ΔSBP was defined as end of procedure SBP minus mean SBP at different time intervals (15-60 minutes, 1-6 hours, 6-24 hours post-procedure). The primary outcome was the poor functional outcome (90-day modified Rankin Scale 3-6).

Results:
We included a total of 267 patients (130 in the intensive treatment group). Compared to patients with favorable outcome, patients with poor outcome had lower ΔSBP (less SBP reduction) at all times intervals. After adjusting for potential confounders including baseline SBP, both ΔSBP
15-60M
and ΔSBP
6-24H
were associated with lower odds of poor outcome (adjusted odds ratio [aOR] per 5mmHg SBP reduction, 0.89; 95% confidence interval [CI] 0.81 to 0.99, and aOR 0.82; 95% CI 0.73 to 0.92, respectively). Concerning safety outcomes, patients with intraparenchymal hemorrhage (IPH) had lower ΔSBP at all time intervals. ΔSBP
15-60M
was associated with lower odds of any IPH (aOR per 5mmHg SBP reduction 0.91, 95% CI 0.83 to 0.99). Conversely, ΔSBP was not associated with mortality or neurological deterioration at any time interval.

Conclusion:
After successful reperfusion, ΔSBP had a linear relationship with poor outcome and the risk of poor outcome was higher with less reduction from the baseline SBP.
Abstract 40: Endovascular Treatment With Or Without Intravenous Alteplase For Acute Ischemic Stroke Due To Basilar Artery Occlusion
Authors: Nie Ximing , Liu Liping
Published: February 2022

Background and Purpose:
It remains controversial if endovascular treatment (EVT) can improve the outcome of patients with acute basilar artery occlusion (BAO). This study aims to compare the functional outcomes between EVT with and without intravenous thrombolysis (IVT) first in patients with acute ischemic stroke (AIS) caused by BAO.

Methods:
AIS patients with BAO who underwent EVT within 24 hours of onset were enrolled in this multicenter cohort study, and the efficacy and safety were compared between the IVT+EVT and direct EVT. The primary outcome was the 90-day functional independence (modified Rankin Scale of 0-2). All outcomes were assessed with adjusted odds ratio (aOR) from the multivariable logistic regression. In addition, a meta-analysis was performed on all recently published pivotal studies and incorporating these studies on functional independence after EVT in BAO patients.

Results:
Of 310 BAO patients enrolled, 241 (78%) were treated with direct EVT and 69 (22%) with IVT+EVT. Direct EVT was associated with a worse functional outcome (aOR, 0.46 [95% CI, 0.25-0.87]; P =0.02). IVT+EVT was associated with a lower percentage of patients who needed ≥ 3 passes of the stent retriever (10.14% vs 20.75%). The meta-analysis regression revealed a potential positive correlation between bridging with IVT first and functional independence (r, 0.14 [95% CI: 0.05-0.24]; P<0.01).

Conclusions:
This study showed that compared to direct EVT, EVT with standard IVT first was associated with better functional outcomes in BAO patients treated within 24 hours of onset. The meta-analysis demonstrated the similar favorable efficacy of IVT first followed by EVT in BAO patients.
Abstract 42: The Effect Of Anesthesia On Thrombectomy Outcomes Is Modified By Collateral Flow:
Pooled Patient Level Analysis From EXTEND-IA, EXTEND-IA TNK Part I And II, And SELECT
Authors: Sarraj Amrou , Albers Gregory , Hassan Ameer , Abraham Michael G , Blackburn Spiros , Hussain Muhammad , Tekle Wondwossen , Ortega-Gutierrez Santiago , Aghaebrahim Amin N , Haussen Diogo C , Toth Gabor , Budzik Ronald , Pujara Deep K , Hicks William J , Vora Nirav , Edgell Randall C , Slavin Sabreena , Lechtenberg Colleen G , Maali Laith N , Qureshi Abid Y , Rosterman Lee , Aertker Benjamin , Abdulrazzak Mohammad A , Mir Osman , Parsha Kaushik N , Reddy Sujan S , Alenzi Bader , Cai Chunyan , Almaghrabi Tareq S , Shaker Faris , Kamal Haris , Arora Ashish , Yassi Nawaf , Sharma Gagan J , Kleinig Timothy J , Shah Darshan , Wu Teddy Y , Martin-schild Sheryl B , Day Arthur L , sitton clark W , Mitchell Peter J , Gupta Rishi , Lansberg Maarten G , Nogueira Raul G , Donnan Geoffrey A , Davis Stephen , Grotta James C , Campbell Bruce C
Published: February 2022

Background:
The effect of anesthesia choice on endovascular thrombectomy (EVT) outcomes is unclear. Collateral status on perfusion imaging may help identify the optimal anesthesia choice.

Methods:
In a pooled patient level analysis of EXTEND-IA, EXTEND-IA TNK, EXTEND-IA TNK part II and SELECT, EVT Functional outcomes (mRS distribution) were compared between general anesthesia (GA) vs non-general anesthesia (non-GA). Further, we assessed the impact of collateral flow on perfusion imaging evaluated by hypoperfusion intensity ratio (HIR) - Tmax10 sec/Tmax6 sec) on the association between anesthesia type and EVT outcomes.

Results:
Of 731 treated with EVT, 305 (42%) received GA and 426 (58%) non-GA. The baseline characteristics were similar, except for presentation NIHSS (median [IQR] GA 18 [13-22], non-GA 16[11-20], p<0.001) and ischemic core volume (GA 14.1mL [3-37] vs non-GA 9mL [0-31], p=0.002). GA was associated with longer LKW to arterial access (203min [158-267] vs 186min [138-252], p=0.002), but similar procedural time (36min [23-59] vs 34min [22-54], p=0.36). Non-GA was independently associated with improved functional outcomes (adj cOR 1.42, 95%CI 1.05-1.93, p=0.024) and lower mortality (17% vs 11.3%, p=0.025). Patients with poor collaterals (HIR≥0.4) had improved functional outcomes with non-GA (adj cOR 1.53, 95%CI 1.02-2.29, p=0.038), while no difference was observed in those with good collaterals-HIR<0.4 (adj cOR 1.38, 95% CI 0.84-2.27, p=0.21).

Conclusion:
GA was associated with worse functional outcomes after EVT, particularly in patients with poor collaterals. These findings have implications for randomized trials of GA vs non-GA.
Abstract 43: Comparative Effectiveness Of Routine Tenecteplase Thrombolysis In Acute Stroke Compared With Alteplase: An INternational Collaboration (CERTAIN Collaboration): Rates Of Symptomatic Intracranial Hemorrhage
Authors: Warach Steven J , Ranta Anna , Song Shlee S , Gibson Daniel , Wallace Adam , Beharry James , Bladin Christopher , Kleinig Timothy J , Harvey Jackson , Doss Vinodh T , Marescalco Ruth , Fink John N , Kim Joosup , Cadilhac Dominique A , Wilson Duncan , Figueroa Sonia , Pech Marco A , Paletz Laurie B , Castro Marissa , Sahlein Daniel , Lafranchise E F , Sandall Justin , Geraghty Scott R , Cullis Paul A , Malisch Tim , Neill Terry A , LaMonte MP , Campbell Bruce , Wu Teddy Y
Published: February 2022

Introduction:
Despite pharmacological and practical advantages for tenecteplase (TNK) over alteplase (ALT), no differences were observed in percent of symptomatic intracranial hemorrhage (sICH) in randomized trials (fewer than 900 total patients for either treatment). We compared rates of sICH in patients treated with either drug, using a large, multicenter, international registry.

Methods:
The CERTAIN collaboration is an ongoing registry of deidentified patient-level data of thrombolytic treated ischemic stroke from various hospitals/programs in New Zealand, Australia, and the United States that have used ALT or TNK since July 1, 2018. Standardized data were abstracted and harmonized from local or regional clinical registries. We defined sICH as clinical worsening of at least 4 points on NIHSS, attributed to parenchymal hematoma, subarachnoid or intraventricular hemorrhage. We used logistic regression for binary variables, adjusting sICH differences for age, baseline NIHSS, thrombectomy, and source hospital network and Mann-Whitney test for continuous baseline variables.

Results:
A total of 7891 patients were included in the initial analysis. The TNK group was older, more likely to be male, had higher NIHSS, and more frequently underwent mechanical thrombectomy (Table. Sample Characteristics). The sICH rate was 3.71% for ALT and 2.13% for TNK: adjusted OR (95%CI) = 0.49 (0.31-0.76) p=0.002. For patients not undergoing thrombectomy after thrombolytic, the sICH rate was 3.00% for ALT and 1.74% for TNK, adjusted OR (95%CI) = 0.48 (0.27-0.87), p=0.016. For thrombectomy treated cases, sICH rate was 6.80% for ALT and 2.80% for TNK, adjusted OR (95%CI) 0.60 (0.31-1.16), p=0.129.

Conclusion:
In this preliminary analysis from a large, multicenter registry, ischemic stroke treated with tenecteplase was associated with a lower rate of sICH than with alteplase. An updated analysis with patient data from additional sites will be presented at the Conference.
Abstract 6: A Comparison Of The Modified Rankin Scale And Stroke Impact Scale-ADL For Measuring Function After Stroke
Authors: Cramer Steven C , Saver Jeffrey L , McGee Breann , Cao Madelyn , Jubb Ashley , Holman Alison ,   The STRONG Study Team
Published: February 2022

Introduction:
The modified Rankin Scale (mRS) of clinician-rated global disability is commonly used to measure functional outcome after stroke but has limitations such as low granularity and ceiling effects. Measures of functional outcomes with higher resolution could provide improved insights into outcomes and therapeutic efficacy. Here we evaluated the performance of the mRS in relation to the Stroke Impact Scale v2.0 Activities of Daily Living score (SIS-ADL), a valid, reliable, patient-reported measure of post-stroke function.

Methods:
Patients in the STRONG Study were examined 90 d post-stroke. In addition to the mRS, exam included the SIS-ADL, which asks patients to rate the difficulty of performing 10 ADLs using a 5-level Likert Scale. SIS-ADL scores range from 0-40; higher scores indicate better function.

Results:
For 499 patients, age = 61.5±14.8 (mean±SD), acute NIHSS = 4 [2-9] (median [IQR], day 90 mRS median = 2 [1-3], and day 90 SIS-ADL median = 35 [26-39]. The d90 SIS-ADL correlated with d90 mRS (r = -0.74, p<.0001). The mean SIS-ADL value decreased with increasing mRS scores, as expected, but there was substantial overlap in SIS-ADL scores across mRS levels (Figure) to a degree beyond the minimal clinically important difference (5.9 points). The SIS-ADL was sensitive to mild deficits, identifying persistent ADL problems in 30/66 (45.5%) patients with a perfect mRS score of 0.

Conclusions:
In a population of mild-moderate stroke, the SIS-ADL identified a wide range of patient-reported functional deficits within each mRS level and was sensitive to functional deficits not identified by the mRS. The SIS-ADL complements the mRS for measuring functional outcome after stroke and may be useful for study design and sample size estimates for acute stroke and stroke recovery trials.
Abstract 71: Cognitive Impairment And The Risk Of Incident Stroke In Hypertensive Patients
Authors: de Havenon Adam H , Sharma Richa , Falcone Guido J , Sheth Kevin N
Published: February 2022

Background:
Research has shown that post-stroke cognitive impairment is associated with worse functional outcome and stroke recurrence, but has not fully explored if cognitive impairment is associated with the risk of first-ever clinical stroke.

Methods:
We performed a post-hoc analysis of non-stroke SPRINT trial participants randomized to either a systolic blood pressure target <140mm Hg versus <120mm Hg. The primary outcome was incident stroke (ischemic and hemorrhagic). The study exposure was the baseline Montreal Cognitive Assessment (MoCA) score, into categories of <20, 20-25, and 26-30. We fit Cox models adjusting for age, race, sex, randomization arm, baseline blood pressure, atrial fibrillation, prior TIA, diabetes, and smoking. We verified the proportional hazards assumption of our Cox model.

Results:
We included 9126 patients (mean age 67.9, males 64.4%, non-Hispanic white 57.8%), of which 169 (1.8%) developed incident stroke during a mean follow-up of 3.8±0.9 years. The rate of stroke in the MoCA categories was 32/2713 (1.2%) for MoCA 26-30, 85/4649 (1.8%) for MOCA 20-25, and 50/1764 (2.8%) for MoCA <20 (p<0.001). In the adjusted Cox model, compared to the reference of MoCA 26-30, the hazard ratio for stroke was 1.42 (95% CI 0.94-2.14, p=0.099) in MoCA 20-25 and 2.22 (95% CI 1.38-3.56, p=0.001) in MoCA <20. The Kaplan-Meier curve for the MoCA stratification is presented in Figure 1.

Conclusion:
Severe cognitive impairment (MoCA <20) is a significant risk factor for incident stroke in hypertensive patients. Further research is needed to understand the mediators of this observation, in particular the control of vascular risk factors during follow-up.
Abstract 73: Blood-based Biological Aging Measures Are Easy-to-access Biomarkers For Detection Of Incident Stroke
Authors: Waziry Reem , Belsky Daniel , Kothari Meeraj , Gu Yian , Boehme Ameila
Published: February 2022

Introduction:
The relationship between biological age and stroke remains unclear. We assessed the role of six DNA methylation and physiology-based biological aging measures as biomarkers of stroke risk.

Methods:
Participants (N=3520, mean age=69±9 years) in the US Health and Retirement Study’s 2016 Venous Blood and DNA methylation studies. Biological aging measures included: Horvath, Hannum, GrimAge, Levine, Pace of Aging (POA) and Phenotypic Age. The clocks and POA were based on DNA methylation and Phenotypic age was based on serum physiology biomarkers (albumin, creatinine, glucose, C reactive protein, lymphocyte percent, mean cell volume, red blood cell distribution width, alkaline phosphatase, and white blood cell count). All measures were regressed on chronological age and residual values were computed. Multivariable logistic regression and three-way decomposition models were conducted. Total, direct and indirect effect of modifiable risk factors (smoking, BMI, blood pressure, diabetes mellitus, and education) on stroke through biological aging was assessed.

Results:
A total of 291 incident strokes were included. Individuals who were biologically older had higher odds of stroke with statistically significant estimates for GrimAge (DNA methylation-based) OR (95%CI): 1.32(1.07, 1.62), P=0.009 and PhenoAge (physiology-based) OR: 1.39(1.15, 1.69), P=0.001. In tertiles analysis (lowest tertile as reference), the odds of a new stroke were two to three times higher in biologically older individuals: GrimAge OR 3rd tertile: 2.42(1.08, 5.42), P=0.03; PhenoAge OR: 3.49(1.60, 7.65), P=0.002. Modifiable factors that showed highly significant indirect effect on incident stroke through biological aging are smoking, high blood pressure, diabetes mellitus and education (college or above).

Conclusions:
Biologically older individuals have 2 to 3 folds higher odds of new stroke occurrence compared to biologically younger individuals. The time lag between biological aging acceleration and manifestation of clinical disease is an opportunity for interventions targeted towards primary stroke prevention.
Abstract 74: Area Deprivation Index, Stroke Outcomes, And Structural Changes To Improve Access To Thrombectomy
Authors: Marayati Naoum Fares , Morey Jacob , Zhang Xiangnan , Weiss Kevin , Rossitto Christina , Chada Deeksha , Dangayach Neha S , Fifi Johanna
Published: February 2022

Introduction:
In New York City (NYC), expanding the reach of thrombectomy-capable stroke centers (TSC) is key to combating socioeconomic disparities in stroke care. The Area Deprivation Index (ADI), a validated, neighborhood-level composite measure (scored 1-100) that includes income, education, employment, and housing quality, has informed healthcare delivery but has not been used to identify disadvantaged neighborhoods with poor access to stroke care. We sought to evaluate the impact of establishing Mount Sinai Queens Hospital (MSQ) as a TSC in 2017 on transfer times and to explore the association between ADI and stroke care access.

Methods:
Thrombectomy patient pick-up addresses were obtained through Emergency Medical Services runsheets from June 2016 to July 2021 and matched to census-tract level ADI scores from Neighborhood Atlas. Preliminary analyses compared both ADIs and time to stroke care access in both Queens and Manhattan. The primary outcome measure was the duration between ambulance arrival and groin puncture. Simple linear regression and T-tests were used to assess the association between ADI and time to groin puncture by borough.

Results:
Among 517 cases between 2016-2021, the average ADI of pick-up locations was 10.35 (range: 1 - 70.5). Across all centers, higher ADI (greater deprivation) was significantly associated with increased time to groin puncture (p = 0.024). Notably, Queens patients were picked up in census tracts with higher ADI (p=0.0289) but had a faster pick up to groin puncture time (p=0.006).

Conclusions:
Across urban census tracts, a higher ADI was associated with delays in access to thrombectomy. Thrombectomy centers in areas with higher ADI can play a role in reducing healthcare disparities for stroke patients.
Abstract 77: Collateral Status And Recanalization After Endovascular Treatment For Acute Ischemic Stroke
Authors: Uniken Venema Simone , Dankbaar Jan , Wolff Lennard , van Es Adriaan , Sprengers Marieke , van der Lugt Aad , Dippel Diederik W , Van Der Worp H B
Published: February 2022

Background:
Successful recanalization and good collateral status are associated with good clinical outcome in patients with acute ischemic stroke treated with endovascular treatment, but the relationships among them are unclear.

Methods:
We analysed data from the MR CLEAN Registry, a multicenter prospective cohort study of patients with acute ischemic stroke who underwent endovascular treatment in the Netherlands. Collateral status was assessed using a common 4-point visual grading scale. Successful recanalization was defined as an extended Thrombolysis in Cerebral Infarction score ≥ 2B. Functional outcome at 90 days was determined with the modified Rankin Scale score. We assessed, in multivariable (ordinal) logistic regression models, the associations between 1) collateral status and successful recanalization, 2) successful recanalization and functional outcome, 3) collateral status and functional outcome. An interaction term (successful recanalization*collateral grade) was added to the latter model, to assess effect modification. Subgroup analyses were performed for patients treated with intravenous thrombolysis.

Results:
We included 2717 patients, 1898 (70%) with successful recanalization. There was no relationship between collateral status and successful recanalization. Successful recanalization (acOR 2.15, 95% CI 1.84-2.52) and better collateral grades (Grade 1, acOR 2.12, 95% CI 1.47-3.05; Grade 2, acOR 3.46, 95% CI 2.43-4.92; Grade 3, acOR 4.16, 95% CI 2.89-5.99) were both associated with a shift towards better functional outcome. There was no significant interaction between collateral status and successful recanalization. Results were similar for patients treated with intravenous thrombolysis.

Conclusions:
Collateral status is not associated with the probability of successful recanalization after endovascular treatment and does not modify the association between successful recanalization and functional outcome.
Abstract 78: A Single Center Comparison Of Transradial And Transfemoral Approaches For Carotid Angioplasty And Stent Placement
Authors: Kumar Nitish , Bhagavan Sachin , ISHFAQ Muhammad F , Yelam Anudeep , Obi Chinedu , Jaura Attiya , French Brandi R , Siddiq Farhan , Gomez Camilo R , Qureshi Adnan I
Published: February 2022

Context:
Transradial access has been increasingly utilized for neurointerventional procedures including carotid angioplasty and stent placement (CAS) over the past decade. At our center, we adopted transradial approach as the preferred approach in 2020.

Objective:
To compare the results of transradial approach with transfemoral approach for CAS as part of a quality assurance initiative.

Methods:
We analyzed data collected for all non-urgent CAS procedures performed at our institute in the last 24 months by same interventionalists to minimize inter-operator variability. We looked at the rates of technical failure; hemorrhagic complications classified as major (hemoglobin decrease >5 g/dL or intracranial hemorrhage with deficits), minor (hemoglobin decreases 3-5 g/dL or intracranial hemorrhage without residual deficits), or insignificant; and any stroke and/or death within 1-month post procedure.

Results:
A total of 182 non-urgent CAS procedures were performed at our institution; 116 (64%) were initiated using transfemoral approach and 66 (36%) were initiated using transradial approach. The median age was similar between the two group (66.5 years versus 66.7 years). There were 6 (3%) CAS procedures initiated using transradial approach but later converted to transfemoral due to anatomical and/or technical difficulties. One (0.6%) CAS procedure initiated using transfemoral approach was converted to transradial approach due to severe iliofemoral atherosclerosis. The rates of any stroke and/or death were 1.6% (n=1) and 3.3%% (n-=4) in patients undergoing CAS using transradial and transfemoral approaches, respectively. The rate of major hemorrhagic complications were 1.6% (n=1) and 5.7% (n-=7) in patients undergoing CAS using transradial and transfemoral approaches, respectively.

Conclusions:
The rates of major hemorrhagic complications were lower among patients who underwent CAS via transradial approach compared with CAS using transfemoral approach although the rates of technical failure remain relatively high with transradial approach.
Abstract 81: Shear-activated Nanoparticle Aggregates Containing Nitroglycerin Selectively Increase Collateral Perfusion During Experimental Ischemic Stroke
Authors: Beard Daniel , Litman Magdalena , Azarpeykan Sara , Uzun Oktay , Bhatta Deen , Buchan Alastair M , Spratt Neil , Ingber Donald
Published: February 2022

Introduction:
Leptomeningeal collateral flow is a strong predictor of stroke outcome. Enhancing collateral flow is an appealing therapeutic approach. However, previous attempts to enhance collateral flow with vasodilators have failed, due to systemic hypotension and cerebrovascular steal from the penumbra. We have shown that during experimental stroke collaterals have fluid shear stress that is 3-7 times higher (100 dyne/cm
2
) than other blood vessels. This unique feature of collateral vessels provides a way to selectively enhance flow, using nanoparticle aggregates loaded with nitroglycerin (NG-NPAs), that only release drug in areas of high shear stress (≥ 100 dyne/cm
2
).

Hypothesis:
Shear-activated NG-NPAs will selectively enhance collateral perfusion and improve stroke outcome.

Methods:
Proximal occlusion of the middle cerebral artery (MCAo) was induced for 70 min in male Spontaneously Hypertensive Rats. Changes in cerebral blood flow in the collateral-supplied ischemic MCA territory, and in the contralateral homotypic region were measured by laser speckle contrast imaging. Animals were randomized to receive I.V. infusion of blank-NPA (B-NPA, control, 4mg in 2ml of saline, n=7) or NG-NPA (50μg NG in 4 mg NPA = 4μg/kg/min of NG, n=7), commencing 25 minutes after MCAo, until reperfusion. Infarct volume was measured at 24 h.

Results:
NG-NPA significantly increased collateral perfusion by 44% vs. 11% for B-NPA at 40 minutes post-infusion (p=0.026), without altering perfusion in the contralateral region (NG-NPA: +19%, B-NPA: +13% of pre-infusion baseline, p=0.99) and without reducing blood pressure (NG-NPA: 161 mmHg, B-NPA: 163 mmHg, p=0.99). NG-NPA significantly reduced infarct volume at 24 h (NG-NPA: 70 mm
3
, B-NPA: 121 mm
3
, p=0.005). Better collateral perfusion was correlated with smaller infarct volume (R
2
= 0.44, p=0.012).

Conclusion:
Shear-activated NG-NPA selectively enhanced collateral perfusion to penumbral tissue without inducing systemic side effects, which resulted in smaller infarcts in this model. Given the known importance of collateral flow, shear-activated NG-NPA show great promise as a potential therapy for ischemic stroke patients, both pre-reperfusion therapy and in those unsuitable for such therapies.
Abstract 83: Stroke-induced Gut Microbiota Dysbiosis Regulates Microfold Cells In Peyer’s Patches
Authors: Honarpisheh Pedram , Banerjee Anik , Ko Kyung Ae , Honarpisheh Parisa , Venna Venugopal R , McCullough Louise , Lee Juneyoung
Published: February 2022

Microfold or membranous cells (M cells) are specialized antigen sampling cells residing in the epithelium of Peyer’s patches (PPs), the gut-associated lymphoid tissue in the small intestine. M cells are in continuous crosstalk with luminal microbes and host immune cells. The detrimental shift of the microbiota seen with aging and after stroke contribute to bacterial antigen translocation. This axis has emerged as an epicenter for post-stroke immune dysfunction and systemic infection. The role of M cells in the PPs as an initiation site for host mucosal immunity after stroke is undefined.

Hypothesis:
Stroke-induced gut dysbiosis and M cell ablation leads to impaired antigen sampling mechanisms and clearance of translocating bacteria in PPs after stroke. We used a 60-minute reversible middle cerebral artery occlusion model in young (8-10 wks) C57BL/6 male mice to investigate how brain ischemia affects M cells in the PPs. We performed microbiota transplants from the cecal contents of stroke mice to naïve age-matched recipients via oral gavage for three consecutive days before tissue harvest on day four. We determined that stroke-induced changes in gut microbiota alone can cause M cell dysfunction. We found that both the number of PPs and M cells decrease 24 hours after stroke (n=8/gp,
p=0.0104
and
p=0.0054,
respectively). Our imaging studies revealed disruption of tissue architecture and reduction in size of PPs after stroke. Microbiota transplant from stroke mice cecum to naïve recipients showed a similar effect on the number of PPs and M cells (n=10/gp,
p=0.0568
and
p=0.0299
). The decrease in the number of M cells after microbiota transplantation was associated with immune dysregulation in the PPs, such as a reduction in the number of regulatory T cells (n=5/gp,
p=0.0084
). This is the first study that specifically examined M cells in a mouse model of stroke. Our results show that 1) stroke reduces the number of PPs and M cells and 2) stroke-induced gut dysbiosis can independently reduce the number of PPs and likely M cells and may regulate gut-originated immune responses after stroke. Future studies are needed to understand the effects of stroke-induced dysbiosis on M cell-mediated antigen processing in the gut and their immunoregulatory functions.
Abstract 84: The Role of IRF5-IRF4 Regulatory Axis in Stroke in Aged Mice: A Translational Study
Authors: Ngwa Conelius , Qi Shaohua , Xu Yan , Liu Fudong , Sharmeen Romana
Published: February 2022

Introduction:
Inflammatory responses are a fundamental pathological consequence of stroke, in which microglial activation plays a central role. Our previous study has found interferon regulatory factor 5 (IRF5) and 4 (IRF4) regulate microglial activation in young stroke mice. However, whether the IRF5-IRF4 regulatory axis has the same effect in aged brains is not known. Numerous neurochemical changes occur with aging, and stroke mainly affects the elderly. Therefore, to study the IRF5-IRF4 axis with aged animals is clinically more relevant and translational. In this study, we exclusively used aged mice (18-20 months) to examine the role of IRF5-IRF4 axis in stroke.

Methods:
Aged, microglial IRF5 or IRF4 conditional knockout (CKO) male mice (with LysM
Cre
) were subjected to a 60-min middle cerebral artery occlusion (MCAO) (n=6/gp for stroke and =4/gp for sham). Infarct volumes and neurological deficits were quantified at 3d after MCAO. Flow cytometry was performed to evaluate microglial activation and peripheral leukocyte infiltration in the ischemic brain. ELISA was conducted to determine the plasma cytokine levels.

Results:
IRF5 CKO mice had significantly smaller cortical infarct size than the flox controls (48.07±5.51% vs. 66.9±5.51%, p=0.0206); larger infarct volumes were seen in IRF4 CKO vs. flox controls in the cortex and hemisphere (Cortex: 58.93±5.16% vs. 38.38±5.16%, p= 0.0049; Hemisphere: 68.73±5.16% vs. 44.63±5.16%, p=0.0008). Significantly improvement on the corner test and neurological deficit score was seen in IRF5 CKO vs. flox mice, and an opposite pattern showed in IRF4 CKO vs. flox controls. Flow cytometry showed IRF5 CKO microglia had significantly lower levels of IL-1β and CD68 than controls; whereas significantly higher levels of IL-1β and TNF-α were seen in IRF4 CKO vs. control microglia. Plasma levels of IL-6 and IL-12 p
40
were decreased in IRF5 CKO vs. flox mice, and the anti-inflammatory cytokines (IL-4/IL-10) levels were higher in IRF5 CKO, and lower in IRF4 CKO mice vs. their flox controls respectively.

Conclusion:
IRF5 signaling drives microglial pro-inflammatory responses and is detrimental to stroke; whereas IRF4 signaling leads to a microglial anti-inflammatory response and protects against ischemia in aged mice.
Abstract 93: Utility Of Routine Inpatient Echocardiography In Acute Ischemic Stroke Patients With Established Stroke Etiology: A Population Study
Authors: Aziz Yasmin N , Kandregula Krishna , Sucharew Heidi , Alwell Kathleen , Woo Daniel , Demel Stacie , Ferioli Simona , Khatri Pooja , Adeoye Opeolu M , Flaherty Matthew L , Mackey Jason , De Los Rios La Rosa Felipe , Martini Sharyl R , Mistry Eva , Coleman Elisheva R , Jasne Adam , Slavin Sabreena , Walsh Kyle B , Star Michael , Haverbusch Mary , Kissela Brett , Kleindorfer Dawn O
Published: February 2022

Background:
Acute ischemic stroke (AIS) remains a leading cause of mortality and disability worldwide, with stroke etiology having an important role in work-up, management, and prognosis. The current AHA/ASA guidelines cite routine echocardiography as reasonable but not mandatory for the work-up of ischemic stroke. We sought to identify how often transthoracic echocardiogram (TTE) results would show a potentially treatment-altering finding.

Methods:
Using the Greater Cincinnati/Northern Kentucky Stroke Study (GCNKSS) for years 2005, 2010, and 2015, we selected patients with a new diagnosis of AIS using ICD-9/10 codes in adults ≥18yrs of age presenting to the emergency department and who had a TTE with stroke etiology of Cardioembolic, Small Vessel, or Large Vessel. All cases were physician reviewed and stroke etiology determined based on our epidemiologic criteria. Demographic information, medical history, electrocardiograms with atrial fibrillation (Afib), and TTE features were collected for each patient and compared across stroke etiology groups using Wilcoxon rank sum test and chi-square test, or Fisher’s exact test, as appropriate.

Results:
There were 5,490 patients presenting with AIS in the GCNKSS in 2005, 2010, and 2015 and 3,984 (73%) had a TTE performed. Of those with TTE, 2,422 (61%) had a presumed etiology of Small Vessel, Large Artery Atherosclerosis (LAA), or Cardioembolic (120 identified as “Other,” 1442 identified as “Undetermined”). Potential findings of TTE that could change management were 1% in Small Vessel, 2% in LAA, and 7% in Cardioembolic etiology strokes.

Conclusion:
In patients presenting with Small Vessel or LAA stroke etiologies, routine inpatient TTE rarely had management-changing findings. Future studies are needed in order to assess cost effective use of TTE in patients with established stroke etiology.
Abstract 99: Single Cell RNA-Sequencing Reveals Array Of Immune Activation States In Intracerebral Hemorrhage
Authors: Johnson Conor W , Askenase Michael H , Beatty Hannah E , DeLong Jonathan H , Zhang Le , Sheth Kevin N , Cord Branden , Hebert Ryan , Matouk Charles , Sansing Lauren H
Published: February 2022

Introduction:
Secondary inflammation is a well-established cause of injury in intracerebral hemorrhage (ICH). One potential treatment for ICH limits inflammation through targeted metabolic modulation of immune cells, but leukocyte activation states in ICH are poorly defined. Using single-cell RNA sequencing (scRNA-seq) of patient hematoma evacuates, we characterized the inflammatory and metabolic profile of over a dozen identifiable leukocyte populations. This research provides insight into the dynamics of immune activation in ICH.

Methods:
Evacuated hematoma and peripheral blood samples from 8 ICH patients (62 ± 2.1 years) were collected via minimally invasive surgery (n=5) or craniotomy (n=3) (Fig. 1a). Collection time ranged from 0 to 4 days after ICH onset (1.5 ± 0.5 days). scRNA-seq was done on the 10X Genomics platform and analyzed using Seurat. Human monocyte-derived macrophage cultures were stimulated with S100A9 and IL-1β, two ICH-relevant inflammatory molecules, or LPS. Echinomycin and 2-deoxy-D-glucose were used to inhibit HIF signaling and glycolysis respectively.

Results:
Clustering revealed over a dozen transcriptionally distinct CNS-resident and immune cell types, many of which have little prior study in ICH (Fig. 1b). 3,395 differentially expressed genes between hematoma and peripheral blood (p<0.05) were found in CD14
+
monocytes and 932 in CD4
+
effector T cells. Pathway analysis found upregulation of HIF signaling, glycolysis, and correlated networks of cytokine expression in the hematoma. The findings were significant across all immune populations but most prominent in myeloid cells (Fig. 1c). Inhibition of HIF and glycolysis in human macrophages
in-vitro
abrogated inflammatory and reparative cytokine production following inflammatory stimulation. In conclusion, this work highlights the interplay of inflammation and metabolism at a single cell level in ICH, contributing to knowledge of the immune response to brain injury.
Abstract NS3: Telemedicine Impact On Post-stroke Outpatient Follow-up In An Academic Healthcare Network
Authors: Lemuel-Clarke Manet , Antwan Marlyn , Henriquez Laura , Belagaje Samir R , RANGARAJU Srikant , Mosley Ashlee , Cabral Jacqueline , Walczak Teri , Ido Moges , Hashima Patricia , Bayakly Rana , Jaffe James , Sutherly-Bhadsavle Loretta , Brasher Cyndy , Danaie Elham I , Victor Patricia , Westover Deborah , Webb Mark , Skukalek Susana L , Barrett A M , Esper Gregory J , Nahab Fadi
Published: February 2022

Introduction:
The expansion of telemedicine associated with the COVID-19 pandemic has influenced outpatient medical care. The objective of our study was to determine the impact of telemedicine on post-acute stroke clinic follow-up.

Methods:
With this retrospective cohort study, we evaluated the impact of telemedicine in Emory Healthcare, an academic healthcare system of comprehensive (CSC) and primary stroke centers (PSC) in Atlanta, Georgia, on post-hospital stroke clinic follow-up. We compared the frequency of successful post-hospitalization follow-up in a centralized subspecialty stroke clinic among patients hospitalized before the local COVID-19 pandemic (January 1- February 28, 2020), during (March 1- April 30, 2020) and after telemedicine implementation (May 1- December 31, 2020). A comparison was made across network hospitals less than 1 mile (CSC) and 25 miles (PSC25) from the specialty stroke clinic.

Results:
Of the 553 ischemic stroke patients [median age 68 years (IQR 58-79), median NIHSS 4 (IQR 1-8)] discharged home or to a rehab facility during the study period, 241 (43.6%) had follow-up in the Emory Stroke Clinic (CSC=48%, PSC25=23%). Overall, 90-day follow-up increased from 31% before to 48% after telemedicine implementation. Similarly, telemedicine appointments increased from 19% to 72% of the follow-up visits. The increase in follow-up visits was modest among CSC patients, from 41% to 51% (p=0.16), relative to the increase among PSC25 patients (5.3% to 31%, p=0.002).

Conclusions:
Telemedicine implementation at an academic healthcare network successfully increased post-stroke discharge follow-up in a centralized subspecialty stroke clinic for hospitalized patients up to 25 miles from the clinic site. However, more work is required to facilitate follow up in the majority of patients.
Abstract NS7: Steps To An Early And Successful Adoption Of Iv Tenecteplase By A Large Integrated Medical System
Authors: Zrelak Patricia A , Hansen Karen L , Meighan Melissa M , Snow Kathryn
Published: February 2022

Background:
In 2020, a large integrated healthcare system consisting of 21 stroke centers implemented IV tenecteplase as the first line pharmaceutical treatment for acute ischemic stroke (AIS) prior to universal adoption in national clinical practice guidelines and FDA approval for stroke.

Purpose:
To describe the steps taken for successful implementation of IV tenecteplase as a first therapy for AIS in 21 stroke centers, part of an integrated system.

Methods:
Pre-implementation steps included gaining systemwide acceptance, especially from key stakeholders such as emergency department staff, patient care services, tele-stroke and neurology physicians, as well as risk management. We addressed potential impacts to related to reimbursement, stroke certification, and national award status. Inclusive changes were made to related policy and procedures, order sets, and other documentation. Standardized training and beta-testing were conducted and a sequential roll-out implemented along the real-time central monitoring.

Results:
Stakeholder groups were engaged prior to implementation with town halls and in-person and desktop simulation exercises. Beta-testing took place in August 2020 with three pilot sites with full system wide implementation by Nov. 2020. Since full implementation, tenecteplase is the only thrombolytic that has been ordered (n=423). Door in door out times have decreased (median 131 minutes pre- to 88 minutes post; p<0.05). In addition, symptomatic ICH rates have decreased by greater than 50% (p<0.05) and there are no reports of systemic bleeding or angioedema.

Conclusion:
Tenecteplase has been shown to be safe and feasible as a first line thrombolytic within our organization. Strong nurse and physician leads, as well as thoughtful and inclusive implementation steps were key in the successful adoption of this system-wide change.