bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract WP112: Thrombolysis for AIS in the Unwitnessed or Extended Therapeutic Time Window: A Systematic Review and Meta-Analysis
Authors: Katsanos Aristeidis H , Malhotra Konark , Sarraj Amrou , Barreto Andrew , Köhrmann Martin , Krogias Christos , Catanese Luciana , Shoamanesh Ashkan , Ahmed Niaz , Caso Valeria , Schellinger Peter D , Alexandrov Andrei V , Tsivgoulis Georgios
Published: June 2021

Introduction:
We sought to assess the utility of intravenous thrombolysis (IVT) treatment in acute ischemic stroke (AIS) patients with unclear symptom onset time or outside the 4.5 hour time window, selected by advanced neuroimaging.

Methods:
We performed random-effects meta-analyses on the unadjusted and adjusted for potential confounders associations of IVT (alteplase 0.9 mg/kg) with the following outcomes: 3-month favorable functional outcome [FFO, modified Rankin Scale (mRS) scores: 0-1], 3-month functional independence (FI, mRS-scores: 0-2), 3-month mortality, 3-month functional improvement (assessed with ordinal analysis on the mRS-scores), symptomatic intracranial hemorrhage (sICH) and complete recanalization (CR).

Results:
We identified 4 eligible RCTs (859 total patients). In unadjusted analyses IVT was associated with higher likelihood of 3-month FFO (OR=1.48, 95%CI:1.12-1.96), FI (OR=1.42, 95%CI:1.07-1.90), sICH (OR=5.28, 95%CI:1.35-20.68) and CR (OR=3.29, 95%CI:1.90-5.69), with no significant difference in the odds of all-cause mortality risk at three months (OR=1.75, 95%CI: 0.93-3.29). In the adjusted analyses IVT was also associated with higher odds of 3-month FFO (OR
adj
=1.62, 95%CI:1.20-2.20), functional improvement (OR
adj
=1.42, 95%CI: 1.11-1.81) and sICH (OR
adj
=6.22, 95%CI: 1.37-28.26). There was no association between IVT and FI (OR
adj
=1.61, 95%CI: 0.94-2.75) or all-cause mortality at three months (OR
adj
=1.75, 95%CI: 0.93-3.29). No evidence of heterogeneity was evident in any of the analyses (I
2
=0).

Conclusion:
IVT in AIS patients with unknown symptom onset time or elapsed time from symptom onset more than 4.5 hours, selected with advanced neuroimaging, results in a higher likelihood of complete recanalization and functional improvement at three months despite the increased risk of sICH.
Abstract WP117: Therapeutic Hypothermia in Patients With Malignant Ischemic Stroke and Hemicraniectomy: A Systematic Review and Meta-Analysis
Authors: Kuczynski Andrea , Demchuk Andrew , Almekhlafi Mohammed
Published: June 2021

Introduction:
Numerous animal models have demonstrated the efficacy of mild to moderate therapeutic hypothermia (TH) in reducing cerebral edema and conferring protection after ischemic injury. We investigated whether TH had a beneficial effect in stroke patients after hemicraniectomy (HC).

Methods:
A MEDLINE systematic review was performed. Inclusion criteria included: ≥10 patients with acute malignant ischemic stroke having undergone HC, studies published in full in the English language, and studies reporting on clinical outcome and complications.

Results:
Thirty-four studies met our search criteria. Six studies with 302 patients with malignant ischemic stroke (TH: n=146, HC alone: n=156) were included. Age, and initial median NIHSS were comparable between the two groups. All studies used systemic TH; four utilized combined TH (venous endovascular and surface cooling), while one study used systemic surface and one used systemic venous endovascular TH. TH was initiated within 37.2 hours (range 24-42 hours) from onset for a median target temperature of TH was 33.6°C (range 33-35°C) and maintained for a median of 72 hours (range 48-96 hours). Target temperature was achieved within 4.5 hours (range 2-36 hours). All studies used rewarming (3 active rewarming). Clinical outcomes at follow-up were not different (follow-up modified Rankin’s 0-2; RR 1.04, 95% CI 0.60-1.80, p=0.9; Figure 1). Cardiac complications were greater in TH (RR 1.79, 95% CI 1.16-2.76, p<0.01). A suggestion of greater mortality was seen with TH (RR 1.43, 95% CI 0.97-2.10, p=0.07), and was significantly greater in studies that did not actively rewarm patients (RR 1.65, 95% CI 1.04-2.60, p<0.05).

Conclusions:
Clinical and functional outcomes were comparable between patients undergoing systemic TH vs. normothermia following HC despite higher complications associated with TH.
Abstract WP120: Welcoming the New Kid on the Block; The Phase IIb Prospective, Randomized, Open-Label, Blinded Endpoint (PROBE) Study of NanO
2
TM
Neuroprotection in Large Vessel Strokes
Authors: Brown Aliza , McGonigle John , Graham Kaitlin , Onteddu Sanjeeva , Radvany Martin , Culp William , Unger Evan
Published: June 2021

Background:
NVX-208 (NanO
2
TM
) was recently examined in a completed randomized, placebo-controlled and double-blinded dose escalation Phase Ib/II safety trial in acute ischemic stroke (AIS) patients and was found to be safe in all dosage levels. Exploratory aims indicated early treatment in the highest NanO
2
TM
dose cohort improved clinical outcomes of early NIHSS and 90-day mRS. In the current Phase 2b protocol, NanO
2
TM
’s enhanced oxygen delivery from the blood to tissue will be examined in early AIS subjects with large vessel occlusions (LVO). LVO patients will provide the optimal assessment for NanO
2
TM
to maintain penumbra tissue viability. The Phase 2b primary objective will be to assess functional recovery and subject independence.

Drug information: NanO
2
TM
is an emulsion of 2% dodecafluoropentane (DDFP) in stabilizers (sucrose, PEG-Telomer-B) and phosphate buffered saline (pH 7.0) that is a highly efficient fluorocarbon oxygen transporter. Compared to previously developed fluorocarbon oxygen carriers, NanO
2
TM
carries far more oxygen per gram of fluorocarbon. Because DDFP is not metabolized, almost 100% of administered doses was recovered in the subject’s breath as DDFP.

Hypothesis:
NanO
2
TM
given early to subjects with LVO ischemic stroke will maintain penumbra tissue viability.

Methods:
Phase 2b study sites will include multiple stand-alone and hub and spoke systems located across the United States. Central IRB and safety monitors will provide oversight and support coverage. Key methodology includes providing early first dosage administration of NanO
2
TM
or placebo (study treatment) to identify and consent LVO AIS subjects with viable penumbra. For drip and ship patients, second and third doses will be given en route or after arrival at the hub hospital and after revascularization procedures, respectively. Following the third dose, all subjects will receive study treatment dosing out to 24 hours, each dose at 90 minute intervals. 24-hour imagery assessments will confirm infarct volume. All final angiograms and 24-hour imaging data will be sent to core labs for blinded confirmatory review. Subject recovery and independence will be assessed throughout the study to 90 days.

Conclusion:
Study projected start date is early to mid-2020.
Abstract WP121: Incorporating CT-Perfusion Imaging in Acute Stroke Therapy Workflow Does Not Delay Door to Needle Time for Intravenous t-PA
Authors: Sianati Bahareh , Cerejo Russel , Wright David , Tayal Ashish , Noah Patty , Heintz Rebekah
Published: June 2021

Introduction:
Brain perfusion imaging has become an integral part of acute stroke therapy, especially for the extended time window. A streamlined workflow is essential to reduce delays in acute stroke therapy. Incorporating standard and advanced imaging together may reduce time to endovascular therapy but may delay administration of intravenous (IV) tPA.

Method:
A retrospective analysis of all acute stroke therapy cases between August 2017 and March of 2018 was performed at a single stroke center. Brain perfusion imaging was instituted into the workflow in December of 2017. We included patients who received IV tPA before and after implementation of CT perfusion (CT-P). Demographics, clinical presentation, stroke treatment times and imaging characteristics were collected.

Results:
During the eight-month period, we identified 117 patients who met inclusion criteria. We divided the cohort into two groups, pre CT-P implementation (Group 1) and post CT-P implementation (Group 2). We identified 66 patients in Group 1 and 51 patients in Group 2. In Group 1, 29 (44%) were females with median age of 63 years. In Group 2, 33 (65%) were females, with median age of 72 years. There was no difference in median times for door to needle in Group 1 (57 minutes, interquartile range [IQR] 42 – 76) compared to Group 2 (53 minutes, [IQR] 40 – 68) (
P
= 0.20).

Conclusion:
Incorporating CT-P in the imaging workflow did not delay door to needle time for IV tPA in acute stroke therapy.
Abstract WP123: Risk Factors and Nomogram to Predict Intracranial Hemorrhage in Stroke Patients Undergoing Thrombolysis
Authors: Zhang Yurong , Yin Xiaoyan , Liang Simin
Published: June 2021

Introduction:
Identification of stroke patients at risk of postthrombolysis intracranial hemorrhage (ICH) in the clinical setting is essential. We aimed to develop and evaluate a nomogram for predicting the probability of intracranial hemorrhage (ICH) in acute ischemic stroke patients undergoing thrombolysis.

Methods:
A retrospective observational study was conducted with 287 participants from a single center (67.2% males, median age 65 years). The patients were randomly divided into a training set (160) and a validation set (127). Univariate and multivariate logistic regression analyses of clinical variables were performed to screen for significant prognostic factors. Nomograph that included significant prognostic variables was formulated to predict ICH. Areas under curve (AUC) of receiver operating characteristic (ROC) and calibration plots were formulated to evaluate the predictive accuracy of the nomograph.

Results:
A total of 41(14.3%) ICH events occurred. A nomogram was developed to predict ICH based on three variables in the training set: the presence of atrial fibrillation (OR: 4.01,
P
=0.009), the National Institutes of Health Stroke Scale (NIHSS) score (OR: 1.16,
P
=0.001) and glucose (OR: 1.37,
P
=0.006) on admission. The AUC-ROC for the training set was 0.817 (0.730-0.925), and for the validation set was 0.809 (0.710-0.904). Calibration plots showed good consistency between the two sets.

Conclusion:
We developed an easy-to-use nomogram model based on 3 independently clinical factors to predict ICH. The nomogram could be useful for individualized prediction of ICH in intravenous thrombolysis-treated stroke patients..
Abstract WP127: Intravenous Administration of Microrna-122 Mimic for Treatment of Ischemic and Hemorrhagic Strokes in Rats
Authors: Liu DaZhi
Published: June 2021

MicroRNAs(miRs)are very promising next generation drug targets due to their unique miR-target binding that is different from the traditional ligand-receptor. A single miR binds to complementary bases in the 3’ untranslated regions(3’UTR) of hundreds of target genes and down-regulates these genes. MiR therapeutics have been developed for treatment of various diseases, with several miR drugs(e.g., miR-122/miR-155 inhibitors, miR-16/29/34 mimics) being advanced into human trials in the last decade. Our previous studies showed that intravenous (i.v.) miR-122 mimic (2.4mg/kg, wrapped in PEG-liposomes) improves outcomes after suture middle cerebral artery occlusion(MCAO)-induced ischemic stroke (IS) with a 6 hour time window. In pilot whole genome miR expression studies, we demonstrated that microRNA-122 (miR-122) is the most significantly decreased miR in blood after intraventricularautologousfresh blood-induced intracerebral hemorrhage (ICH) in rats. As compared to sham controls, miR-122 decreased 28 fold at 3 hrs, 34 fold at 24 hrs, 31 fold at 7 days and 19 fold at 14 days in blood after ICH in rats. These miRNA expression data suggest that elevating miR-122 in blood has great potential to treat ICH in addition to IS. Therefore, we hypothesized that i.v. miR-122 mimic improves outcomes after ICH, in addition to IS. Our miR-122 targetome studies show that a set of miR-122 target genes (Pla2g2a, Vcam1, Nos2, Rhbdf1, Olig1, Nrep) are responsible for the therapeutic efficacy of miR-122 mimic on ischemic stroke, while another set of genes (Ywhaq, Klrk1, Tpst1, Vars2)account for efficacy in ICH. Using3’UTR luciferase reporter assays and anti-sense Morpholino Oligos (MOs), we show that miR-122 binds to 3’UTR of its target genes Pla2g2a and Vcam1, rather than Nos2. In addition,
in vivo
MO-miR-122-Pla2g2a blocks miR-122 mimic treatment-induced decrease of Pla2g2a in blood cells after ischemic stroke. In summary, our data suggest miR-122 mimic can treat IS and ICH. Therefore, the miR-122 mimic treatment for IS and ICH could likely be performed without brain imaging (e.g. in the ambulance, and/or emergency room) since it is broadly efficacious for both IS and ICH.
Abstract WP128: Stroke Subtype Predicts Neurological Deterioration After Intravenous Alteplase for Acute Ischemic Stroke
Authors: Allen Alexander , Dakay Katarina , Ricci Brittany , Chang Andrew , Mac Grory Brian , Cutting Shawna , Burton Tina , Jayaraman Mahesh , McTaggart Ryan , Lord Aaron , Furie Karen , Yaghi Shadi
Published: June 2021

Introduction:
Intravenous alteplase improves functional outcome in patients with acute ischemic stroke. While patients often have better outcomes, other patients may experience recurrent or worsening symptoms. We sought to determine the association between stroke subtype and neurologic deterioration in this study cohort.

Methods:
Data were abstracted from a prospective quality improvement registry at a comprehensive stroke center. Patients with symptomatic intracranial hemorrhage, no follow-up imaging, code status change to comfort measures only in the first 24 hours, or stroke mimics were excluded. Recurrent cerebrovascular events (RCVE) were defined as any new or worsening symptoms due to cerebral ischemia in the absence of intracranial hemorrhage or an alternative etiology such as infection or seizure. We compared demographic factors, vascular comorbidities, admission blood pressure, medications, use and timing of antithrombotics during hospitalization, admission NIH stroke scale, endovascular intervention, stroke subtype [Cardioembolic, large artery atherosclerosis, small vessel disease, cryptogenic, and other defined (such as dissection, hypercoagulability, cancer related, illicit drug use)], and good 90-day outcome (mRS 0-1) between the two groups using Fisher’s exact test and t-test as indicated. We then performed multivariable logistic regression analyses to determine associations between stroke subtypes and RCVE.

Results:
We identified 705 patients treated with tPA, and 606 met the inclusion criteria. The rate of RCVE was 5.8% (35/606). In multivariable analyses, when compared to cardioembolic/cryptogenic stroke, RCVE was more common in small vessel disease (adjusted OR 9.51 p=0.029), large vessel disease (adjusted OR 5.60, p=0.033), and other stroke mechanisms (adjusted OR 11.29, p=0.019). RCVE was associated with more disability at 90 days when compared to non-RCVE (median mRS 4, IQR 3 vs. median mRS 3, IQR 2, p = 0.016).

Conclusions:
Non-cryptogenic/Non-cardioembolic stroke subtypes are associated with early RCVE, and RCVE is associated with long term disability. Studies are needed to confirm our findings and test interventions optimizing stroke prevention strategies in these subtypes.
Abstract WP129: The Heat Grading Scale as a Neurovascular Remodeling Based Score in Aneurysms Treated With Flow Diversion
Authors: Kirmani Jawad F , Fourcand Farah , Kulhari Ashish , Singh Amrinder , Ro Daniel , Barbery Daniela , Shaikh Azka , Zacharatos Haralabos , Steineke Thomas , Mehta Siddhart
Published: June 2021

Objective:
To apply principles of neurovascular remodeling in the classification of flow diverted aneurysms to predict outcomes using the HEAT (Hemodynamics, Endothelialization and Aneurysmal Thrombosis) grading scale.

Introduction:
The goal of flow diversion is to exclude an aneurysm from circulation through endothelialization of the aneurysmal neck and hemodynamic induction of aneurysmal thrombosis. Current grading scales do not include the above parameters to evaluate aneurysms after flow diversion.

Methods:
Reconstructions using 360° virtual reality (VR) models based on volumetric digital subtraction angiography (DSA) scans of unruptured, wide-neck intracranial aneurysms treated with Pipeline™ from March 2010 to May 2018 at our comprehensive stroke center were built using Surgical Theatre
®
. The HEAT grading scale was used to generate a 0 to 15-point score that evaluated residual filling (none 0%, entry remnant <5%, subtotal 5-95%, total >95%), stasis phase (persistent contrast at venous phase, clearance before venous phase, arterial clearance before capillary phase), endoleak (absence, presence), free-hanging edge (absent, present without thrombus, present with thrombus), in-stent stenosis (0-29% minimal, 30-49% mild, 50-69% moderate, 70-94% severe, 95-99% critical), and branch filling (complete, partial TICI 2b >50%, partial TICI 2a <50%, insufficient). Each case was assigned a HEAT score by four neurointerventionalists using DSA, CT angiography (CTA), and the VR model.

Results:
Fifty out of 86 Pipeline™ cases had 3D rotational DSA and met technical standards required to build the VR model. Clinical adverse events including central retinal artery occlusion, middle cerebral artery syndrome, and amaurosis fugax were positively associated with HEAT score (n=3, p=<0.001) as were subclinical adverse events including endoleak (n=2) and free-hanging edge with thrombus (n=2) (p=<0.001). Interrater variability was high (k=0.8).

Conclusion:
The HEAT grading scale is sensitive, reproducible, and associated with clinical outcome. Larger prospective studies are warranted to validate our results.
Abstract WP13: Left Ventricular Systolic Dysfunction is Associated With Poor Functional Outcomes and Mortality After Endovascular Thrombectomy for Acute Ischemic Stroke
Authors: Tan Benjamin Y , Leow Aloysius ST , Sia Ching-Hui , Sunny Sibi , Ng Zhi-Xuan , Yeo Joshua YP , Chia Magdalene LJ , Wong Lily YH , Widjaja Louis , Gopinathan Anil , Yang Cunli , Chan Bernard PL , Teoh Hock Luen , Seet Raymond CS , Paliwal Prakash R , Sharma Vijay K , Yeo Leonard LL
Published: June 2021

Background:
Endovascular thrombectomy (ET) has transformed acute ischaemic stroke (AIS) therapy in patients with large vessel occlusion (LVO). Left ventricular systolic dysfunction (LVSD) decreases global cerebral blood flow and predisposes to hypoperfusion. We evaluated the relationship between LVSD as measured by LVEF, and clinical outcomes in patients with anterior cerebral circulation LVO who undergo ET.

Methods:
This retrospective study examined patients from our AIS endovascular thrombectomy registry from 2013-2018. We included all consecutive patients who had anterior circulation LVO (ICA, M1, M2) who underwent ET, and had transthoracic two-dimensional echocardiography. LVSD was measured by assessment of the LVEF using Simpson’s biplane method of discs according to American Society of Echocardiography guidelines. LVSD was defined as a reduced LVEF of <50%. Primary outcome was defined as good functional outcome using a modified Rankin Scale (mRS) of 0-2 at 3-months.

Results:
Of 254 AIS patients with anterior circulation LVO, we included 229 patients with complete echocardiography assessment. On multivariate analyses, older age, diabetes mellitus, lower ASPECTS, unsuccessful recanalization, smaller LV outflow tract diameter and LVSD were significantly associated with poor functional outcomes (Table 1). On ordinal (shift) analyses, LVSD was associated with an unfavourable shift in the mRS outcomes (OR 3.09, 95% CI 1.68 - 5.69,
p
< 0.001) after adjusting for age and ischemic heart disease (Figure).

Conclusion:
Anterior circulation LVO AIS patients with LVSD have poorer outcomes after ET, suggesting the need to tailor peri-procedural management strategies.
Abstract WP136: Peripheral Activation of Gut-Immune-Brain Axis in Cerebral Amyloid Angiopathy
Authors: d'Aigle John , Honarpisheh Pedram , Won William W. , Blixt Frank , Miranda-Sohrabji Darius F. , Blasco Conesa Maria P. , Maniskas Michael , Lee Juneyoung , Urayama Akihiko , Bryan Robert M. , McCullough Louise D. , Ganesh Bhanu P.
Published: June 2021

Cerebral Amyloid Angiopathy (CAA) is an emerging cause of vascular cognitive impairment in the elderly. CAA is characterized by amyloid-β (Aβ) deposition in the central nervous system (CNS) vasculature and is associated with increased neuroinflammation. Aging is risk factor for CAA and is accompanied by low-grade inflammation and gut dysbiosis (a pathological imbalance of microbial organisms in the gut). Activation of peripheral immunity by a dysfunctional gut-immune axis may contribute to CAA progression. We hypothesize that CAA-induced gut dysbiosis leads to activation of a peripheral immune response which can accelerate CAA progression. We used the Tg-SwDI mouse (harboring Swedish, Dutch, and Iowa mutations of human amyloid precursor protein (APP), “CAA mice”) model that develops cerebral Aβ deposits and cognitive deficits around 3-4 months. We used 2mo mice as pre-onset and 10mo mice as post-onset groups.

Results:
Our preliminary fecal 16S rRNA sequencing data showed higher microbiome alpha- (or “within-sample”) diversity in CAA mice (n=207, Inverse-Simpson diversity score, p=0.036). Upon visualization of beta- (or “between samples”) diversity in CAA and WT animals, with weighted-UniFrac-distances by principal coordinate analysis (PCoA), we found a notable clustering by strain (34.6% and 26.4% PCoA axes, p=0.001). Immunophenotyping of liver showed significant decrease in the B:T cell ratios when comparing the pre- to post-onset CAA mice (0.53 vs. 0.19, p = 0.005). Additionally, we observed a significant increase in the relative frequency of MHC-II (high) non-myeloid cells, when comparing the pre- to post-onset CAA (11.5% vs. 41.8%, p = 0.027).

Conclusion:
Our findings suggest that gut dysbiosis occur early in CAA pathogenesis and may be responsible for
ongoing
increased peripheral and CNS inflammation. This work is significant if follow-up studies confirm that manipulation of the gut microbiota can modulate the peripheral immune response to reduce neuroinflammation in CAA and improve CAA-associated cognitive phenotype.
Abstract WP137: Time-Course Characterization of Blood-Brain Barrier Disruption in Secondary Thalamic Injury After Stroke
Authors: Cao Zhijuan , Harvey Sean , Pendharkar Arjun , Chiang Terrance , Cheng Michelle , Steinberg Gary
Published: June 2021

Introduction:
A secondary degenerative injury occurs in the thalamus after primary cortical ischemic stroke. This secondary thalamic injury progresses long-term and is associated with somatosensory dysfunctions. Blood-brain barrier (BBB) disruption is one of the feature pathological changes in primary ischemic stroke, but whether BBB disruption happens in the secondary thalamic injury is unclear. In this study, we aim to investigate the BBB changes during the development of secondary thalamic injury after stroke.

Methods:
Cortical ischemic stroke was generated by permanent occlusion of the left middle cerebral artery on male C57BL6J mice (12-15 weeks). BBB permeability was assessed by Biocytin-TMR (869 Da, 1mg/mL) at post-stroke days (PD) 1, 3, 7, 14, 28, 56, and 84. Immunostainings of CD68 (inflammation) and CD31 (vascular morphology) were performed. Brain sections were imaged with Confocal LSM800 and quantified by NIH ImageJ and Wimasis Image Analysis. BBB permeability related genes were quantified by real-time PCR among naïve, PD7 and PD28.

Results:
In ipsilesional thalamus (iTH), the Biocytin-TMR was detected as early as PD3 in the secondary thalamic injury area and persisted until at least PD84. The fluorescence intensity of Biocytin-TMR significantly increased during PD28-84 and peaked at PD56, suggesting the BBB is chronically disrupted in iTH. Compared to naïve animals, stroke animals exhibited significant increase in tube length, total number of tubes and total number of branching points at PD56 and PD84. mRNA expression of
ZO-2
significantly down-regulated at PD7 and returned to baseline levels by PD28. mRNA of
Angiopoietin-1
(
Ang-1
),
VEGFa
and
Adam10
were significantly increased at PD28.

Conclusion:
Our data demonstrate that the BBB disruption begins early at PD3 and continues to progress until PD84 in the secondary degenerative thalamus. This BBB disruption is accompanied by changes in blood vessel morphology and permeability related genes. Current studies are examining the expression of key genes at PD56 using qPCR and immunohistochemistry. Our results will elucidate the cellular and molecular changes of BBB disruption involved in thalamic injury, which will provide potential targets for enhancing stroke recovery.
Abstract WP14: Higher Aspiration Force Improves Technical Outcomes in ADAPT Thrombectomy for Ischemic Stroke
Authors: Chalhoub Reda M , Alawieh Ali M , Korson Clayton , Anadani Mohammad , Lena Jonathan , Spiotta Alejandro
Published: June 2021

Introduction:
Aspiration thrombectomy using the direct aspiration at first pass technique (ADAPT) has been shown to be non-inferior to stent-retriever thrombectomy in ischemic stroke trials. Favorable outcomes after ADAPT are dependent on successful recanalization and lower number of aspiration attempts. We investigated the impact of aspiration force on technical and clinical outcomes of ADAPT by modulating two underlying determinants, the aspiration catheter size and the reperfusion pump power.

Methods:
We performed a retrospective analysis of patients undergoing ADAPT thrombectomy between 01/2018 and 02/2019. Patient treated using ADAPT were included irrespective of age, onset to groin or whether thrombolytic therapy was administered. Patient demographics and outcomes were reviewed from patient charts and thrombectomy procedure notes. Patients were dichotomized based on the reperfusion pump used (MAX, 28.5 inHb power vs ENGINE, 29.2 inHg power) and further split into the different reperfusion catheters used.

Results:
This study included 194 patients who underwent ADAPT thrombectomy during the study period with mean age of 69, and of which 48% were females. Comparing patients treated with two different reperfusion pumps, ENGINE (N=73) and MAX (N=118), similar rates of favorable outcomes measured by 90-day modified Rankin score (mRS) were observed. However, patients in the ENGINE groups had significantly shorter procedure time (20 vs 27 min, p<0.05), lower number of aspiration attempts (1.9 vs 2.2 p<0.05), and low rates of rescue stent retriever therapy (14% vs 33%, p<0.05). The use of ENGINE was an independent predictor of shorter procedure time (p<0.05) and lower rates of symptomatic hemorrhage (p<0.1) compared to MAX pump. There was no significant difference in procedure time and rates of functional outcomes among patients undergoing ADAPT using different sizes of large bore catheters ACE 60, ACE68 and Jet 7.

Conclusion:
Success of ADAPT thrombectomy is dependent on successful aspiration of the occluding clot, and is dependent on the aspiration force. Higher aspiration forces can be achieved by increasing the power of reperfusion pump leading to better technical outcomes without increased complication rates.
Abstract WP140: Activation of Endothelial Ras-Related C3 Botulinum Toxin Substrate (Rac) 1 Improves Post-Stroke Recovery and Angiogenesis via Activating P21 Activating Kinases (Pak) 1 in Mice
Authors: Bu Fan , Min Jia-wei , Qi Li , McCullough Louise D , Li Jun
Published: June 2021

Introduction:
Cerebral angiogenesis is correlated with post-stroke prognosis yet its mechanism is far from clear. Accumulating evidence shows that Rac1, a Rho-related GTPase, plays a central role in promoting neovascularization via activating Pak 1 in endothelial cells. We investigated whether activating endothelial Rac1 improved functional recovery and angiogenesis after ischemic stroke.

Methods and Results:
Young male mice were subjected to a 60-minute middle cerebral artery (MCAO) stroke. Endothelial Rac1 was overexpressed by brain injection of lentiviral vectors encoding Rac1 with endothelial promoter ENG the day after MCAO. Treatment improved the recovery of sensorimotor and cognition function assessed by single pellet reaching (day 7: p=0.042; day 14: p=0.012, n=7/group), adhesive removal (day 7: p=0.013, n=7/group) and novel object recognition test (day 21: p=0.045, n=7/group) compared to the control vector group. Follow-up immunofluorescence revealed that ENG-Rac1 promoted angiogenesis as measured by the endothelial proliferation (CD105+BrdU, p=0.016, n=5/group) and the elevation of pericyte (NG2, p=0.008, n=5/group), which is indispensable for stable vessel structure, in the peri-infarct zone, with no effect on brain cavity size. We further explored Rac1 signaling, involving Pak1, in mediating angiogenesis in vitro. Human brain endothelial cell line-5i (HEBC 5i) was subjected to a 16-hour oxygen-glucose deprivation (OGD) followed by re-oxygenation. Rac1 (NSC23766 at 30 μM) and/or Pak1 (IPA3 at 10 μM) inhibitors were incubated with HEBC 5i 24 hours after OGD. Delayed inhibition of Rac1 reduced endothelial proliferation (CCK-8 assay) at 48 hours (p=0.039, n=4/group) and the ability of migration (scratch assay) at 72 hours (p<0.001, n=6/group) after OGD compared to the vehicle control. Similarly, Pak1 inhibition also led in the reduction in proliferation (p<0.001, n=4/group) and migration (p=0.003, n=5/group). No additional inhibitory effect if application of both inhibitors together compared with either inhibitor alone.

Conclusions:
Activation of endothelial Rac1 improves post-stroke recovery and angiogenesis and this pro-angiogenetic effect is mediated by Pak1.
Abstract WP145: Safety of Intra-Arterial Mesenchymal Stem Cells in a Large Animal Model of Stroke: A Dose Escalation Study
Authors: Watanabe Mitsuyoshi , Bates Karen E , Guada Luis , Ramdas Kevin , Khan Aisha , Hare Joshua , Sidani Charif , Contreras Victor R , Saini Vasu , Howerth Elizabeth , Yavagal Dileep
Published: June 2021

Background:
Despite the efficacy of thrombectomy for large vessel occlusion acute ischemic stroke (AIS) , ~50% of patients have significant residual deficits. Pre-clinical data on intra-arterially (IA) administered mesenchymal stem cells (MSCs) in stroke are promising and this approach is attractive for clinical application. While there is a concern for micro-occlusion with IA delivery due to the large size of MSCs, a dose of 1 x 10
5
MSCs given 24-48 hr in a rodent reperfusion middle cerebral artery occlusion (rMCAo) model has been shown to be safe and effective. As per STAIR recommendations, we performed a dose-escalation (DE) study of IA-MSCs in a large animal stroke model.

Methods:
An endovascular canine rMCAo model using retractable platinum coil for 60-120 min was established. At 48 hr post-rMCAo, allogeniec canine MSCs were delivered using a 0.0165” microcatheter in the ipsilateral upper cervical internal carotid artery in escalating doses (based on proportion of rodent to canine total cerebral blood volume). Serial MRIs and neurological deficit scoring (NDS) were performed over 30 days. Animals were euthanized at 15-30 d post-rMCAo and brains were harvested.

Results:
Female canines (n=13), age 12-36 months, weighing 22-26 kg received IA MSCs ranging from 5-80 x 10
6
(M). At doses of 5-40 M IA-MSCs no neurological worsening was observed. Serial NDS and stroke volume on MRI showed no increase post-IA-MSCs and actually showed progressive reduction. A higher numerical reduction was seen in the 10-40 M groups compared to 5 M. However, in the one canine receiving 80 M IA-MSCs, there was significant worsening of the MCA-area infarction and NDS due to microembolization at this higher dose. Gross examinations and histopathology of brain tissue were consistent with ischemia. The brain of a canine receiving 80 M cells showed differentially aged areas of necrosis supporting two ischemic events. Neuroblasts, doublecortin-positive cells, and neovascularization were observed in canine brains suggesting regenerative mechanisms.

Conclusions:
These data suggest that IA-MSCs are safe in a large animal model up to 40 M IA-MSCs and is the maximum tolerated dose in this DE study. Furthermore, our data suggests that up to 40 M IA-MSCs may be promising in exploring efficacy in AIS.
Abstract WP15: Correlation of 24-Hour Infarct Volumes and Imaging Reperfusion With Functional Independence in DEFUSE 3
Authors: Sarraj Amrou , Lansberg Maarten , Marks Michael P , Mlynash Michael , Heit Jeremy J , Savitz Sean I , Albers Gregory W
Published: June 2021

Background:
In DEFUSE 3, infarct volumes 24 hours after randomization did not significantly differ in EVT vs. medical management only (MM) groups. We hypothesized that this lack of difference was due underestimation of the final infarct volume among patients who had persistent penumbral tissue 24 hours after randomization that subsequently progressed to infarction. In this substudy, we evaluated if the 24 hr post-randomization DWI volumes correlated with functional independence.

Methods:
We correlated the 24-hr post-randomization DWI volumes and penumbral profiles with 90-day functional independence.

Results:
182 patients, 92 were randomized to EVT, 90 to MM. 24 hr post-randomization Tmax and DWI volume were assessable for 75 EVT and 69 MM. Infarct volumes at 24 hr follow-up did not differ between EVT and MM median (IQR) ml 35.0 (17.6-81.6) vs 41.0(25.4-106.2), P=0.185. Still, 24 hr infarct volumes independently correlated with 90 day functional independence: median (IQR) 30.3 ml (9.0-55.6) vs. 47.5 ml (25.4-132.3), aOR=0.93 (95%CI=0.89-0.98, P=0.004) for achieving functional independence vs. disability for each additional 5 ml of infarct volume after adjustment for baseline NIHSS, age, glucose, and treatment, figure 1. EVT resulted in higher rates of reperfusion (>90% reduction in Tmax>6 seconds at 24 hrs in 79% of EVT vs. 18% of MM, P<0.001). Patients who achieved successful reperfusion with no evidence of remaining penumbra had smaller 24- hr infarct volumes: 32.9 (17.6-67.0) vs. 59.3 (24.7-126.3), P=0.007), figure 2 and a higher odds of functional independence aOR=10.9, 95%CI 3.6-39.8, P<0.001, compared to those who had remaining penumbral tissue, figure 3.

Conclusion:
24 hr- post randomization infarct volumes independently correlated with functional independence in DEFUSE 3. Patients who had complete reperfusion had smaller follow-up infarct volumes and a higher odds of functional independence as compared to those with persistent penumbral mismatch.
Abstract WP154: The Role of Ethylmethylhydroxypyridine Succinate in the Induction of PGC-1α in Experimental Ischemic Damage of the Prefrontal Cortex
Authors: Shakova Fatima , Kirova Yuliya , Germanova Elita , Romanova Galina
Published: June 2021

The aim of the study was to identify the potential succinate/SUCNR1-mediated mechanism of induction and activation of transcription coactivator PGC-1α (peroxisome proliferator-activated receptor-gamma coactivator 1 alpha) – key activator of the mitochondriogenesis, angiogenesis, fusion of mitochondria, antioxidant defense system that are basis of neuroprotective mechanisms – in the peri-infarction zone of the rat prefrontal cortex (PFC). Focal bilateral damage of the PFC was modeled by photo-induced thrombosis. Ethylmethylhydroxypyridine succinate (a form of succinate passing through the blood-brain barrier; trade name of the drug Mexidol) was injected intraperitoneally 2 hours after infarction and then every day at a dose of 100 mg/kg (7 day course). The tissue of the peri-infarction zone was taken 1, 3, 7 days after the start of therapy, as well as 14 days after discontinuation of the drug. Brain samples were stored in liquid nitrogen, a cytosolic extract was obtained, expression levels of SUCNR1, PGC-1α, transcription factors (NRF1, TFAM), VEGF, catalytic subunits of mitochondrial respiratory enzymes (NDUFV2, SDHA, cyt c1, COX2) and ATP synthases (ATP5A) were determined by Western blot analysis. The study showed that the content of PGC-1α in the peri-infarct zone decreased one day after the induction of ischemic damage by 40% and remained reduced for 21 days after a ischemia. The course of injection of mexidol stabilized PGC-1α in the peri-ischemic zone at a level comparable to the control, both at the stage of treatment and drug withdrawal, and in intact rats induced PGC-1α by 30%. Induction of NRF1, TFAM, NDUFV2, SDHA, cyt c1, ATP5A, indicating the activation of PGC-1α, was observed in rats of the three compared groups, however, the highest expression levels were found in animals subjected to the course of mexidol. Also it was revealed overexpression of SUCNR1 and VEGF in ischemic and intact rats, were injected with mexidol. The study demonstrates for the first time that succinate/SUCNR1 signaling is involved not only in the mechanisms of cerebral angiogenesis, but also in the mechanisms of PGC-1α-dependent neuroprotection. The study opens up new perspectives for pharmacological modulation of PGC-1α levels in the ischemic brain.
Abstract WP16: The Safety and Outcomes of Endovascular Thrombectomy in Stroke Patients on Oral Anticoagulation: The Florida Stroke Registry
Authors: Sur Nicole B , Wang Kefeng , Krementz Nastajjia , Gardener Hannah , Dong Chuanhui , Yavagal Dileep R , Saini Vasu , Gutierrez Carolina , Rundek Tatjana , Sacco Ralph L , Romano Jose G , Asdaghi Negar
Published: June 2021

Background:
Endovascular therapy (EVT ) is the only available reperfusion treatment in acute ischemic patients on prior oral anticoagulants (OACs). We evaluated the practice patterns, safety, and outcomes of EVT in patients on OAC therapy.

Methods:
From 2010 to 2019, 84,346 ischemic stroke patients presenting within 24 hours of symptoms across 107hospitals were enrolled in the Florida Stroke Registry, of which 5,702 received EVT. We collected data on demographics, past history, medications, NIHSS, symptomatic intracranial hemorrhage (sICH), discharge destination and hospital characteristics and used multivariable-adjusted logistic regression models to identify differences in outcome based on anticoagulation status.

Results:
Among all EVT patients (mean age 71±15 years, 48% women), 969 (17%) were treated with OAC. Compared to those not on OACs, anticoagulated patients were older (mean age 75.5±12.8 vs 70.0 ±14.9 years), more women (56% vs 50%), Hispanics (25% vs 20%), Medicare patients (44% vs 34%) and more likely to have atrial fibrillation (78.5% vs 27%), present earlier to the hospital (101 min vs 122 min) with similar clinical severity (median NIHSS 16 vs 15). There was no significant difference in length of stay 0-6 days (OAC 45.7% vs 46.8%), mRS 0-2 (OAC 23.9% vs 30.9%), independent ambulation (OAC 31.1% vs 38.3%), sICH (OAC 6.1% vs 5.4%), life-threatening or serious hemorrhage (OAC 0.4% vs 0.8%) or mortality (OAC 9.8% vs 9.8%) between the two groups. After multivariate adjustment, EVT patients on OACs were less likely to be discharged home compared to patients not on OACs (OR 0.18, 95% CI 0.05-0.31).

Conclusion:
In this large, multi-center study, EVT for patients with acute ischemic stroke on oral anticoagulation therapy did not result in higher rates of sICH, life threatening hemorrhage or death, though these patients are less likely to be discharged directly home.
Abstract WP160: Conivaptan (Combined Vasopressin Receptor Antagonism) Attenuates Cerebral Edema Following Ischemic Stroke in Rodent Model
Authors: Ansari Saeed , Shushrutha Hedna Vishnumurthy , Ganji Sarah , Sadighi Alireza , Krishnan Rashi , Bavarsad Shahripour Reza , Dryn Oleksandra , Khorchid Yasser , Krishnaiah Balaji , Zand Ramin , Waters Michael , Dore Sylvain , Alexandrov Andrei
Published: June 2021

Objective:
To study the potential role of Conivaptan on cerebral edema, infarct volume, neurological deficit and survival.

Introduction:
Although vasopressin has a significant detrimental role in stroke-related cerebral edema, the effect of mixed vasopressin antagonism in stroke has not been well studied. We studied the effects of conivaptan on the course of cerebral edema, severity of neurological deficit, infarct volume, aquaporin-4 (AQP4) protein levels and survival after experimental stroke.

Methods:
Animals were randomized to receive either conivaptan or vehicle after reperfusion of experimental middle cerebral artery occlusion. The severity of neurological deficit, edema, and infarct volume assessments were performed by an investigator blinded to group assignment. All assessments were performed at either 12h or 24h and Western blot was subsequently used to investigate AQP4 levels.

Results:
At 12h, conivaptan-treated mice (n=16) had 6.64±6.50% ipsilateral hemispheric enlargement compared to 16.55±7.05% in control mice (n=16, p=0.0003). Similarly, at 24h, conivaptan-treated mice (n=12) had 6.81±4.63% ipsilateral hemispheric enlargement in comparison to 13.93±5.43% in control mice (n=12, p=0.0023). At 24h, the conivaptan-treated mice had lower neurological deficits in comparison to control (p=0.04). There was no significant effect of conivaptan on infarct size or AQP4 levels in comparison to vehicle, naïve and sham group.

Conclusions:
The present study highlights the role of mixed vasopressin receptor antagonism in reducing cerebral edema secondary to brain ischemia. This data suggests the possibility of developing vasopressin antagonism as a new adjuvant in treatment of stroke-related brain edema.
Abstract WP161: Sovateltide Promotes Regeneration and Functional Recovery of Ischemic Brain by Improving Mitochondrial Function
Authors: Ranjan Amaresh , Hauert Thomas , Hussain Mazin , Giometti Anthony , Briyal Seema , Gulati Anil
Published: June 2021

Mitochondrial dysfunction is associated with cerebral ischemic stroke. Sovateltide (IRL-1620; PMZ-1620) undergoing clinical trials (NCT04047563; NCT04046484) has been demonstrated, in preclinical studies, to provide recovery of brain functions when administered following acute cerebral ischemic stroke. We hypothesize that sovateltide preserves mitochondrial activity and provides neural protection and regeneration. We investigated the effect of sovateltide on mitochondrial morphology and function following acute cerebral ischemic stroke. Rats underwent permanent middle cerebral artery occlusion (MCAO) and then received three intravenous injections of vehicle or sovateltide (5 μg/kg) at 4, 6, and 8 h and sacrificed at 24 h post MCAO. Another set of rats were treated similarly on day 0, 3 and 6 and sacrificed on day 7. Western blot and/or immunofluorescence were used to evaluate protein expression of NeuroD1, DoubleCortin, HUC+HUD, NeuN, Sox2, Oct4, DRP1 and MFN2. Mitochondrial biogenesis was evaluated using
in situ
PCR and transmission electron microscopy (TEM). Sovateltide produced (p<0.001) improvement in neurological deficit and motor function compared to vehicle at 24 h and day 7 post MCAO. Expression of NeuroD1 (p=0.0003), HuC-HuD (p=0.0373) and DoubleCortin (p=0.013) was higher in sovateltide compared to vehicle at 24 h but not at day 7. No change in Oct4 and Sox2 was observed. Immunofluorescence of cultured NPCs showed elevated expression of NeuroD1 and NeuN in sovateltide compared to vehicle. Sovateltide significantly decreased fission marker, DRP1 (p<0.001) and increased fusion marker MFN2 (p<0.0001) at 24 h and day 7 compared to vehicle. A significantly increased mitochondrial DNA (MT-ATP8, mitochondria specific gene) fluorescence in sovateltide group compared to vehicle (p=0.0418) and sham (p=0.0085) was observed. TEM analysis showed significant increase in mitochondrial cross-sectional area x number and % mitochondrial/tissue area in sovateltide group at 24 hours compared to vehicle. Mitochondrial number increased (p=0.032) at day 7 compared to 24 h in vehicle group. Sovateltide preserves mitochondrial activity and provides neural protection and regeneration in rat model of acute cerebral ischemic stroke.
Abstract WP162: Systolic Blood Pressure Night-dipping Influences Functional Recovery in Acute Ischemic Stroke With Severe Cervicocephalic Atherosclerotic Stenosis
Authors: Ma Xin , Kong Qi , Wan Guiling , Xue Sufang , Ren Yi
Published: June 2021

Background and Purpose:
Systolic blood pressure falling by 10-20% of daytime values during the night constitutes a physiological night-dipping pattern. Blunted (<10%) systolic blood pressure night-dipping (SBPN) is a risk factor of acute ischemic stroke (AIS), but the prognostic value of SBPN for patients with AIS remains unclear. Severe (≥70%) cervicocephalic atherosclerotic stenosis (SCAS), different from the mild or moderate stenosis, renders the cerebral perfusion more vulnerable to variations of blood pressure is prevalent in AIS, and may consequently change the relationship of SBPN with AIS outcomes. We sought to examine the association between SBPN and AIS functional recovery, respectively in patients with and without SCAS.

Methods:
Patients with AIS within 6 days were consecutively enrolled and divided into SCAS group and non-SCAS group according to whether there was SCAS on CT angiography. SBPN was evaluated by the night-to-day dipping percentage using 24-hour ambulatory blood pressure monitoring on the 6
th
day after the symptom onset. A reduction in modified Rankin scale score (mRS) after 3 months compared to mRS at admission was defined as functional recovery.

Results:
Among 247 AIS patients, 194 (78.5%) had blunted SBPN, and the mean SBPN percentage was 3.12% ± 7.83% (minimal: -24%, median: 3%, maximal: 22%). AIS patients with blunted SBPN were less likely to have the functional recovery than those with normal SBPN (63.9% vs. 81.1%, p=0.018). There was significant interaction between the SBPN percentage and the presence of SCAS for predicting the functional recovery (p=0.026). In AIS patients with SCAS (n=146), rather than in those without (n=101), the SBPN percentage could serve as an indicator of 3-month functional recovery independently of age, sex, National Institute of Health stroke scale score at admission and traditional risk factors (adjusted odd ratio=1.06 for per percent increase of SBPN, 95% confidential interval: 1.01-1.11).

Conclusions:
Blunted SBPN was frequent among patients with AIS. Adverse effects exerted by lower SBPN on AIS functional recovery were more considerable in patients with SCAS. For AIS patients with SCAS, evaluating SBPN was important to assess their prognosis.