bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract TP119: Upregulation of MicroRNA-128 in the Peripheral Blood of Acute Ischemic Stroke Patients is Correlated With Stroke Severity Partially Through Inhibition of Neuronal Cell Cycle Reentry and Apoptosis
Authors: Liu Ping , Han Ziping , Ma Qingfeng , Wang Rongliang , Tao Zhen , Li Guangwen , Li Fangfang , Zhang Sijia , Ji Xunming , Zhao Haiping , Luo Yumin
Published: January 2019

Aim:
MiR-128, one of the most enriched miRNAs in the human brain, has been reported to protect MCAO mice via inhibiting P38α MAPK. Whether it is involved in pathogenesis in acute ischemic stroke patients remains to be determined. The present study focused on the clinical importance of miR-128 and its underlying mechanisms.

Methods:
MiR-128 levels in the circulating lymphocytes, neutrophils, and plasma of acute ischemic stroke patients were detected by using RT-PCR. Meanwhile, we collected infarction volume, NIHSS and mRS scores, and compare their correlations with miR-128 levels. Bioinformatics analysis was applied to predict inflammation related pathways targeted by miR-128. Then cerebral ischemia was induced by middle cerebral artery occlusion in C57/BL6 mice, and miR-128 levels in the brain tissues were assessed by using RT-PCR. Apoptosis related protein caspase-3 and-12, cell cycle related proteins and pathway molecules were detected in Neuro-2a cells upon H
2
O
2
plus miR-128 stimulation by flow cytometry, and western blot, respectively.

Results:
MiR-128 levels were significantly elevated in the circulating lymphocytes, neutrophils, and plasma of patients with acute ischemic stroke. In addition, the miR-128 levels in circulating lymphocytes positively correlated with the infarction volume, NIHSS scores at 7 days and mRS at 90 days after ischemic stroke onset. Subsequent KEGG pathway analysis showed that the MAPK signaling pathway and cell cycle were among the pathways targeted by miR-128. Although no correlation was found between miR-128 in plasma and peripheral inflammatory cell numbers, miR-128 decreased in the penumbra and increased in the infarction core of ipsilateral brain tissues in MCAO mice. Moreover, the
in vitro
study demonstrated that miR-128 inhibited neuronal apoptosis and reversed cell cycle reactivation induced by H
2
O
2
stimulation; the underlying mechanism involved decreasing cyclin A2 expression and inhibiting phosphorylation of PTEN and ERK.

Conlusion:
The upregulation of miR-128 in circulating lymphocytes of acute ischemic stroke patients was correlated with stroke severity and protected against oxidative stress via inhibiting neuronal apoptosis and cell cycle reentry.
Abstract TP120: Inhibition of α5β1 Integrin With the Small Peptide ATN-161 Reduces Inflammation, Stabilizes the Blood-Brain Barrier, and is Neuroprotective After Experimental Ischemic Stroke
Authors: Edwards Danielle , Salmeron Katie , Lukins Doug , Fraser Justin F , Bix Greg J
Published: January 2019

Endothelial cell integrin receptors, specifically the β
1
subtype, play a direct role in inflammation and blood-brain barrier (BBB) dysfunction, both implicated in poor ischemic stroke outcomes. We hypothesize that inhibition of a particular β1 integrin subtype, α5β1, (a pro-angiogenic fibronectin receptor acutely expressed after ischemic stroke) could be therapeutic in ischemic stroke via BBB stabilization.

Methods:
3-month-old male, C57BL/J6 wildtype mice underwent transient middle cerebral artery occlusion for 1 hour. Mice were treated intraperitoneally with the small peptide α5β1 integrin inhibitor ATN-161 (1 mg/kg) upon reperfusion, post stroke day (PSD) 1 and PSD2. On PSD3, infarct volume (TTC and T2-weighted MRI) and vasogenic edema (MRI) were assessed. Neuroscore, an 11-point functional assessment, was performed on PSD1-14. Expression of MMP-9, claudin-5 and IL-1β levels were determined by qPCR. On PSD3, immunohistochemical analyses of α5 integrin, collagen IV, claudin-5, CD45, and DAPI expression were performed.
In vitro
oxygen-glucose deprivation (OGD) experiments on brain endothelial (bEND3) cells were also performed, evaluating ATN-161 administration (10 μM) effects on BEND3 layer permeability via FITC-dextran migration, and on immunocytochemistry of α5 integrin and claudin-5 expression.

Results:
Acute post-stroke administration of ATN-161 significantly decreased infarct volume and vasogenic edema, and improved functional recovery. Additionally, ATN-161 appeared to stabilize the BBB by increasing expression of the tight junction protein claudin-5, while decreasing expression of the extracellular matrix proteinase, MMP-9, inflammatory cytokine (IL-1β), and infiltrating leukocytes (CD45). Additionally, permeability was conserved with ATN-161 administration following OGD.

Conclusion:
Administration of the α5β1 inhibitor ATN-161 stabilizes the BBB barrier, and reduces inflammatory infiltration, while reducing infarct volume, vasogenic edema, and behavioral dysfunction following experimental stroke. Collectively, these results suggest inhibition of α5β1 via ATN-161 could represent a promising novel therapeutic approach for ischemic stroke.
Abstract TP121: Inhibition of Ezh2 Simultaneously Blocks Pro-Inflammatory Polarization and Enhances
Vegfa
Expression in Male and Female Microglia
Authors: Koellhoffer Edward C , d'Aigle John , Li Jun , McCullough Louise D
Published: January 2019

Background:
Microglia are the innate immune cells of the central nervous system and are poised to be the first responders to ischemic stroke by polarizing to a damaging pro-inflammatory or a reparative anti-inflammatory phenotype. Oxygen glucose deprivation (OGD) alters microglia epigenetic regulation to promote an anti-inflammatory phenotype and up-regulation of
Vegfa
which may enhance angiogenesis after ischemic stroke. Interestingly, OGD down-regulates Enhancer of Zeste Homologue 2 (Ezh2), a histone lysine
N
-methyltransferase associated with repression of anti-inflammatory genes to promote pro-inflammatory polarization.

Hypothesis:
We hypothesized that OGD drives microglial anti-inflammatory polarization through down-regulation of
Ezh2
.

Methods:
We cultured male and female primary microglia from neonatal P0.5-P3 C57Bl/6 mice in phenol red-free DMEM (Gibco) and charcoal stripped FBS (Sigma). Cultures were treated with GSK343 (Cayman Chemical) or DMSO control and exposed cells to OGD (95% N
2
, 5% CO
2
) for 8hrs. Microglia were collected for RNA (Qiagen) and analyzed using real-time PCR (Bio-Rad).

Results:
We found that OGD up-regulated anti-inflammatory genes, notably
Gdf15
,
Il1rn
,
Irf4
, and
Vegfa
while down-regulating pro-inflammatory genes including
Tnfa
,
Il1b
,
Il6
, and
Ccl2
(n=14, p<0.05).
Ezh2
expression was down-regulated with 8hr OGD (p<0.001). Pharmacological inhibition of Ezh2 with GSK343 in OGD resulted in exaggerated down-regulation of
Il1b
and
Il6
(p<0.01) as well as enhanced up-regulation of
Vegfa
(p<0.05). Notably, there were no sex differences identified in our work (n=6-7, p>0.05).

Conclusion:
Our data shows that OGD-induced down-regulation of
Ezh2
is necessary for down-regulation of
Il1b
and
Il6
and up-regulation of
Vegfa
. This may be a novel therapeutic target for ischemic stroke available to both men and women to simultaneously diminish pro-inflammatory gene expression and enhance angiogenesis and functional recovery.
Abstract TP124: Nicotine Alters Brain Energy Metabolism and Exacerbates Ischemic Brain Damage
Authors: Raval Ami P , Patel Sonia P , Diaz Francisca
Published: January 2019

Background:
Smoking-derived nicotine (N) and oral contraceptives (OC) are known to synergistically magnify the risk and severity of cerebral ischemia in females. The underlying pathological mechanism remains elusive. Our studies have shown that N toxicity is exacerbated by OC via altered mitochondrial function, which involved a defect in activity of cytochrome c oxidase, the terminal enzyme of the electron transport chain. However, the effects of impaired mitochondrial function on brain metabolism remain to be investigated. To understand the impact in brain metabolisms, in the current study we investigated the global metabolomic profile of brains of adolescent and adult female rats exposed to N +/- OC.

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

Results:
Pathway enrichment analysis showed significant changes in energy metabolism (glycolysis and TCA cycle) and neurotransmitters in both adolescent and adult rats exposed to N, OC and N+OC in relation to saline treatment. The changes were more pronounced in adolescent rats with a significant decrease in glucose, glucose 6-phosphate, fructose-6-phosphate along with a significant increase in pyruvate in N and N+OC exposed groups when compared to saline (p<0.05), suggesting alterations in the glycolytic pathway. Western blot analyses of glycolytic enzymes support the observed metabolic changes.

Conclusion:
Nicotine and N+OC exposure increased brain glycolysis in an age-dependent manner. Since glucose metabolism is critical for brain physiology, altered glycolysis deteriorates neural function thus exacerbating ischemic brain damage. Moreover, significant decrease in the neuroactive peptide GABA was observed in young female rats treated with N+OC when compared to saline group. Discerning the exact effects of N +/- OC on overall brain metabolism and the molecular mechanisms affecting mitochondrial function at different ages will open a new window for future therapeutic intervention.
Abstract TP125: Temporal Alteration of Infiltrated Macrophage and Resident Microglia Following Focal Cerebral Ischemia Model in Mice
Authors: Oh Yumi , Park Joohyun , Huang Meiying , Barua Sumit , Lee Jong Eun
Published: January 2019

Stroke, a devastating brain damage, is the second cause of adult disability and death following the heart disease worldwide. As the blood supply is insufficient to the brain tissue followed by occlusion of the cerebral artery, molecular cues generated by cerebral ischemia activate the components of innate immunity, promote inflammatory signaling and contribute to tissue damage. Microglia known as an immune cell in the central nervous system (CNS) has functions similar to those of macrophages in the periphery. Moreover, blood-brain barrier (BBB) causes the infiltration of blood-derived macrophages. However, the interaction between the microglia and blood-derived macrophage is still unknown. We used CX3CR1::EGFP transgenic mice to visualize the microglia and blood-derived macrophage dynamics on neuroinflammatory responses.

Methods:
We used CX3CR1::EGFP transcriptional reporter gene mice to visualize the microglia and macrophages to injured brain tissue on neuroinflammatory responses following transient middle cerebral artery occlusion (tMCAO) modeling. Also, we performed two-photon microscopy for intra-vital imaging, time-dependently.

Results:
Our preliminary data showed that it is morphologically possible to distinguish activated microglia and infiltrated macrophages from the resident microglia specifically in FACS and Immunohistochemistry. In addition, blood-derived macrophages and brain microglia showed different polarization patterns by specific markers (Iba1, Tmem119, CD86, CD206, and CD45) in time-dependent manners (n=5 /sham, 6 hours, 1, 3, 5, 7 days) after tMCAO. Furthermore, we performed the cytokine/chemokine array to evaluate the level of specific cytokine/chemokine on ischemic stroke using the brain tissue. In results, the levels of brain tissue of specific cytokine/chemokine showed different levels in all experimental time courses.

Conclusion:
Taken together, the overall data demonstrated that dynamics of microglia and blood-derived macrophage using specific type of transgenic mice could be a novel strategy for regulating the M2 anti-inflammatory microglia phenotype rather than M1 pro-inflammatory microglia and finding the optimal time point of drug treatment attenuating ischemic stroke.
Abstract TP127: Impact of Smoking on Collateral Blood Flow in Patients With Acute Ischemic Stroke With Large Cerebral Artery Embolic Occlusion
Authors: Vilanilam George K , Badi Mohammed K , McCoy Emily G , D'Souza Caitlin E , Becker Tara L , Miller David A , Vibhute Prasanna , Gupta Vivek
Published: January 2019

Introduction:
Good collateral flow is associated with improved outcomes in acute embolic stroke. There is compelling data linking smoking to all types of stroke, with current smokers at a higher risk than former or never smokers. Smoking has, however, been shown to promote collaterals in coronary vascular bed in humans. It is unknown if there is a similar effect in cerebral collateral flow. We aimed to investigate if cigarette smoking was positively associated with collateral blood flow in a homogenous cohort of patients with acute large vessel occlusive embolic stroke.

Methods:
We identified all patients aged ≥18 with acute ischemic stroke showing embolic occlusion of ICA terminus/M1 MCA on admission CT angiography (CTA), between 2008 to 2018, through an institutional database. Patients with chronic occlusions and stenotic lesions were excluded. Individual CTAs were independently reviewed by two trained investigators to calculate collateral scores of the affected hemisphere using the modified Tan scale (0-4) as a reference. Details of cigarette smoking history were obtained from the electronic medical records. Patients were grouped into smokers (former and current smokers) and never smokers. Odds ratios (OR) and their 95% confidence intervals (CI) were estimated, and all tests were considered significant when P<0.05.

Results:
Of the 612 patients identified through the database, 429/612 patients (mean age 71±16 years, 45% [194/429] women) satisfied the inclusion criteria. 64.8% (278/429) had a positive history of smoking with an average of 47±12 pack-years. There was a significant association between good collateral scores (≥2) with smoking history (OR 1.74 CI 1.17-2.61, P=0.006). This trend remained significant even after comparing raw collateral scores (0-4)
(
P=0.006, Spearman’s ρ=0.22). However, number of pack-years and collateral scores exhibited no statistically significant relationship (P=0.6).

Conclusions:
Our study shows that patients who have ever smoked have higher intracranial collateral vessel scores in the event of an acute embolic stroke. Increased impedance and reduced cerebral blood flow resulting from cigarette smoking may stimulate collateral recruitment in cerebral pial circulation, similar to the effect in coronary bed.
Abstract TP129: The Combination of Tissue Plasminogen Activatorand Vepoloxamer Results in Sustained Neuroprotection in Aged Rats After Embolic Stroke
Authors: Wang Chunyang , Zhang Zheng Gang , Chopp Michael , Emanuele Martin , Zhang Li
Published: January 2019

Stroke is a leading cause of death and disability worldwide, mainly affecting the elderly. To date, tissue plasminogen activator (tPA), the only FDA approved treatment agent, is of limited use in stroke patients mainly due to its narrow therapeutic window and hemorrhage complication. Vepoloxamer is a highly purified proprietary amphipathic copolymer, which has potent anti-thrombotic and rheological properties for treating various thrombotic disorders. In an effort to increase the efficacy and safety of tPA thrombolytic therapy, the present study evaluated the neuroprotective effect of combination treatment with Vepoloxamer and a low dose of tPA in aged rats after embolic middle cerebral artery occlusion (MCAO). Male aged rats (18 month) subjected to MCAO were randomly divided into the following groups (n=10/group): tPA alone (5mg/kg, IV) at 2h; tPA (5mg/kg, IV) at 2h in combination withVepoloxamer (300mg/kg at 2h, IV; followed by a 12h IV infusion of 100 mg/kg/hr starting at 10h); or saline at 2h as control. An array of behavioral tests were performed weekly for 4 weeks. Infarct volume was measured 4 weeks after MCAO. The combination treatment with tPA and Vepoloxamer significantly (p<0.05) reduced infarct volume (20±3%) compared with rats treated with saline (31±2%) or tPA alone (32±2%). In addition, the rats treated with tPA in combination with Vepoloxamer exhibited sustained improvements in neurological function up to 4 weeks starting at 1d after MCAO, when compared with rats treated with saline or tPA monotherapy. However, tPA monotherapy failed to reduce neurological functional deficits compared with the saline control. The combination of tPA and Vepoloxamer did not increase the mortality rate nor the incidence of cerebral hemorrhage compared with saline or tPA monotherapy. In conclusion, our data demonstrated that the adjuvant treatment with Vepoloxamer and tPA amplifies the therapeutic efficacy of low-dose tPA in aged rats after embolic stroke without increasing the incidence of hemorrhagic transformation.
Abstract TP13: Safety and Efficacy of Cangrelor in Acute Stenting for the Treatment of Cerebrovascular Pathology: Preliminary Experience in a Single-Center Pilot Study
Authors: Agnoletto Guilherme J , Aguilar-Salinas Pedro , Brasiliense Leonardo B , Santos Roberta , Granja Manuel F , Gonsales Douglas , Aghaebrahim Amin , Sauvageau Eric , Hanel Ricardo A
Published: January 2019

Background and Purpose:
Acute ischemic stroke secondary to tandem occlusions or carotid stenosis alone present treatment challenges, especially when antiplatet therapy is needed for extracranial or intracranial stenting.. To date, there is no standardized approach for antiplatelet inhibition in this acute setting.

Methods:
A single-arm pilot study was performed to assess the safety and efficacy of cangrelor plus aspirin in neurointervention for platelet inhibition in patients who require acute stenting in the setting of ischemic stroke. A standard institution protocol was generated which included 15mcg/kg loading dose followed by 2.0mcg/kg/min infusion. Once post op imaging excluded hemorrhage this was converted to aspirin and brilinta and cangrelor was discontinued.

Results:
A total of 6 patients have been enrolled from October 2017 to July 2018. The median age was 73 years (57.5 - 85.3). At admission, the median NIHSS was 12.5 (2 - 22.3). All of the patients were treated in acute setting per the stroke protocol at our institution. Cangrelor was infusedand all patient achieved an adequate platelet inhibition (< 200 PRU (P2Y12 Reaction Units)). Five out 6 cases, had a proximal carotid stent placed and 1 patient underwent intracranial MCA stenting. None of the patients experienced periprocedural hemorrhagic or thromboembolic complications. There was also no in-stent thrombosis within 24 hours after the intervention. The majority of patients (4/6) had a good clinical outcome at discharge (mRS 0-2).

Conclusions:
Our findings suggest that Cangrelor is a promising alternative in acute stenting for the treatment of cerebrovascular pathology, however, further studies with larger samples are required to accurately elucidate its safety and effectiveness in neuroendovascular procedures.
Abstract TP132: The Combination Therapy of Intravenous Mannitol and Hypoxic Preconditioned Stem Cells for Ischemic Stroke
Authors: Park Dong-Hyuk , Kang Ho-Young
Published: January 2019

Introduction:
Hypoxic preconditioning of stem cells is currently employed as a strategy to prepare stem cells for increased survival and engraftment in the host. Mannitol enhances blood-brain barrier permeabilization and can improves the efficiency of systemically administered stem cells. The aim of this study is to elucidate the neuroprotective effects of combination of intravenous mannitol injection and the preconditioned stem cell transplantation on stroke induced neural injury.

Materials and Methods:
Human adipose stem cells (hADSCs) and mouse induced neural stem cells (miNSCs) were subjected to hypoxic preconditioning by culture in 2% O
2
. 24 hours after middle cerebral artery occlusion, all experimental animals were injected with mannitol intravenously. Five or ten minutes after mannitol injection, vehicle (PBS) or normal hADSCs or preconditioned hADSCs or normal miNSCs or preconditioned miNSCs were intravenously administered to the stroke animals. Neurobehavior functions and infarction volume were compared among the experimental groups. Immunohistochemistry was also performed to reveal the stem cell migration into the brain and histological changes after stem cell implantation.

Results:
Mannitol injection 10 minutes before stem cell transplantation more increased cell permeability compared to that of 5 and 15 minutes (p<0.05). Hypoxic preconditioned hADSCs more improved neurobehavioral deficits compared to any other stem cell groups (p<0.001). Immunohistological studies showed that stem cell treatment increased neuronal proliferation and angiogenesis, and decreased inflammatory reaction. The combination therapy of mannitol and hypoxic preconditioned hADSCs showed more increased neuronal proliferation and angiogenesis compared to any other stem cell groups (p<0.01).

Conclusion:
Based on our data, the combination therapy of mannitol and hypoxic preconditioned stem cells seems to have therapeutic potential for the ischemic stroke. Furthermore, hypoxic preconditioned hADSCs more augmented neuronal proliferation compared to normal hADSCs and preconditioned miNSCs. These findings suggest that hADSCs might be more eligible to hypoxic preconditioning than iNSCs for ischemic stroke.
Abstract TP133: GSNO Pre- and Post-Conditioning Blocks Blood-Brain Barrier Disruption and Improves Endothelial Function in a Mouse Model of Cerebral Ischemia and Reperfusion
Authors: Singh Inderjit , Singh Avtar K , Khan Hamza , Dhindsa Jasdeep S , Khan Mushfiquddin
Published: January 2019

Background:
Endothelial dysfunction is a major risk factor of stroke, and stroke injury itself causes endothelial dysfunction. Endothelial pathology following stroke blocks the mechanisms of neuroprotection and brain repair. Aberrant endothelial nitric oxide synthase (eNOS) activity and its consequent disturbed nitric oxide (NO) metabolome are mainly responsible for endothelial dysfunction. The major NO metabolite S-nitrosoglutathione (GSNO) maintains endothelial function via S-nitrosylation and invokes neuroprotection via activation of Akt. We investigated whether exogenous administration of GSNO mimics beneficial functions of eNOS-derived NO in protecting the neurovascular unit using wild-type and eNOS-deficient mouse models of stroke.

Methods:
Transient cerebral ischemic injury was induced by middle cerebral artery occlusion (MCAO) for 60 minutes in male adult wild-type and eNOS-null mice. GSNO (0.1 mg/kg bw, iv) and GSNO reductase inhibitor N6022 (5mg/kg bw, iv) were administered 30 minutes before MCAO in pre-injury studies and at reperfusion in post-injury studies. Brain infarctions, edema, and neurobehavioral functions were evaluated 24 h after reperfusion. Akt activity was determined by Western blot and immunohistochemistry.

Results:
eNOS-null mice had a higher degree (p<0.05) of injury than wild-type. Pre-MCAO treatment with GSNO significantly reduced infarct volume, decreased edema and improved neurological score, and increased tactile strength in both wild-type and eNOS-null mice compared with untreated, injured animals. Post-ischemic injury GSNO treatment also significantly reduced infarct volume and improved neurological score. N6022 also had effects similar to exogenously administered GSNO.

Conclusions:
Reduced brain infarction and edema, and improved neurobehavioral function by pre-injury exogenous/endogenous GSNO treatment indicate that GSNO-mediated pre-conditioning protects against IR, likely by mimicking the eNOS-derived NO-dependent functions involving Akt activity. Neurovascular protection by GSNO and N6022 in both pre- and post-ischemic injury events support GSNO and/or N6022 as a promising candidate to be evaluated for prevention and protection of humans from stroke injury.
Abstract TP139: MicroRNAs Expression Patterns of Hemorrhagic Transformation After Mechanical Reperfusion for Acute Ischemic Stroke in Rat
Authors: Liu Zhong , Wang Sheng-Wen , Tuo Yong-Hua , Liebeskind David S , Shi Zhong-Song
Published: January 2019

Background:
Severe hemorrhagic transformation (HT) after mechanical thrombectomy and intravenous thrombolysis predicts poor clinical outcome in acute ischemic stroke. The specific roles of microRNAs in the pathogenesis of HT, however, are still unclear. Thus, the aim of this study is to investigate miRNA expression profiles in the rat ischemic brain with HT after mechanical reperfusion.

Methods:
A model of reperfusion-induced HT was established in rats with hyperglycemic challenge and 5h middle cerebral artery occlusion (MCAO) followed by 19h reperfusion. Infarct volume, brain water content, HT, neurological score, and blood-brain barrier damage were determined at 24h after cerebral ischemia. The miRNA expression profiling of rat brain samples in the MCAO group and those in the sham-operated group was performed using the miRCURYLNA Array. The differentially expressed miRNAs were further validated by qRT-PCR. Then, after predicting their target genes from top-ranked miRNAs, the KEGG and GO analyses were further used to predict the associated significant cell signaling pathways and functions.

Results:
Reperfusion with 5h of MCAO induced HT in all hyperglycemic rats, and most of them were the parenchymal hematoma. The results from the miRNA array revealed that 57 miRNAs were significantly altered 24h after reperfusion in the ischemic brain with HT. The expressions of these 57 miRNAs were further verified using qRT-PCR, and 33 top-ranked miRNAs were confirmed. Among them, 30 miRNAs were significantly downregulated and 3 were significantly upregulated in rats with HT. The top-listed downregulated miRNAs included miR-383-5p, miR-335, miR-376a-5p, miR-212-5p, miR-219a, miR-126a-5p. Three miRNAs were significantly upregulated, including miR-125b, miR-195, miR-214. The most enriched pathways are associated with the Hippo signaling pathway which regulates cell survival and death. Twenty significantly regulated miRNAs involve into the Hippo signaling pathway, including miR-383-5p.

Conclusions:
Alteration of the miRNAs in the ischemic brain with HT may serve as biomarkers for HT after mechanical reperfusion in acute ischemic stroke. The role of reperfusion-inducible miR-383-5p and Hippo signaling pathway in the HT requires further investigation.
Abstract TP140: Intra-Arterial Mesenchymal Stem Cell Therapy Modulates Expression of NLRP1 Inflammasome in Animal Model of Ischemic Stroke
Authors: Sarmah Deepaneeta , Vats Kanchan , Saraf Jackson , Kaur Harpreet , Kalia Kiran , Yavagal Dileep , Bhattacharya Pallab
Published: January 2019

Background:
Stroke is one of the leading causes of long-term disability worldwide. Ischemia, followed by acidosis, worsens the pathology by activating the acid sensing ion channel 1a (ASIC1a). This activated ASIC1a increases the expression of NLRP1 inflammasome in a pH dependent manner that further activates the inflammatory cascade. ASIC1a once activated triggers the influx of Ca
2+
ions and its overload contributes to neuronal injury and death in ischemic stroke. Cell based therapy with mesenchymal stem cells (MSCs) is promising for clinical translation and reported to improve neurological outcome in rodent model. We aim to test if intra-arterial (IA) MSCs can inhibit the production of inflammasome by attenuating ASIC1a expression to render neuroprotection.

Methods:
Middle-aged Sprague Dawley rodents were infused with IA MSCs at 6 hours post middle cerebral artery occlusion (MCAo) followed by 24 hours of reperfusion. Rats were evaluated for neurodeficit and motor functions. Brains were harvested for infarct size estimation, biochemical analysis and western blot experiments.

Results:
IA MSCs when given at a dose of 1x10
5
cells at 6 hours following ischemia confer neuroprotection as evident by reduction in infarct volume, improvement in neurodeficit scores and motor function. Increase in GSH levels and reduction in elevated nitrite and MDA levels were observed in the IA MSCs treated animals. IA MSCs infusion also attenuated the expression of ASIC1a, NLRP1, NLRP3, ASC1, IL1β and caspase-1 in the cortical brain regions following ischemia.

Conclusion:
IA MSCs confers neuroprotection by attenuating acidosis by modulating NLRP1 mediated ASIC1a expression.

Keywords:
Ischemic Stroke, Mesenchymal stem cell, Inflammasome, Interleukin-1β, Peri-infarct area
Abstract TP145: Admission Hyperglycemia Predicts Poor Cerebral Collateral Flow in Acute Ischemic Stroke
Authors: Vilanilam George K , McCoy Emily G , Badi Mohammed K , D'Souza Caitlin E , Becker Tara L , Vibhute Prasanna , Gupta Vivek
Published: January 2019

Introduction:
Poor leptomeningeal collateral flow is related to worse neurological outcome in acute ischemic stroke. The increased release of stress hormones during the first hours of acute stroke leads to inhibition of insulin secretion and increase insulin resistance, thus inducing stress hyperglycemia, which is often evident on blood glucose levels at admission. While admission hyperglycemia, independent of diabetes mellitus (DM) is associated with poor clinical outcome in ischemic stroke, studies on its effect on collateral circulation after acute cerebral embolism are largely inconclusive.

Methods:
We identified a consecutive series of patients aged 18 years and older from 2008 to 2018 with acute embolic large vessel stroke confirmed on CT angiography (CTA) using an institutional database. Individual CTAs were over-read, and collateral scores of the affected hemisphere were calculated using a modification of the Tan scale (0-4), by two trained readers. We reviewed the electronic medical records for presenting NIHSS, admission glucose and HbA1C levels, and prior history of DM. Spearman’s ρ, odds ratios (OR), and their 95% confidence intervals (CI) were analyzed. All tests were considered significant when P<0.05.

Results:
Of the 405 patients identified through the database (mean age 70 years [range, 55-85], 45% [183/405] women), 35% (142/405) had a prior history of DM. Mean admission glucose was 134±51 mg/dL, and median NIHSS at presentation was 17. Blood glucose level at admission was negatively correlated with collateral scores (ρ= -0.23, P=0.008). Specifically, glucose levels above 120 mg/dL were significantly associated (OR 1.68 CI 1.13-2.5) with poor collateral scores (≤1). However, collateral scores exhibited no statistically significant relationship with HbA1c (ρ=-0.08, P=0.15) or prior history of DM (P=0.73).

Conclusions:
Patients with higher admission glucose levels have poor collateral scores, while HbA1c and prior DM do not have a similar effect on collateral flow. Our results suggest that poor collateral flow may explain adverse outcomes associated with hyperglycemia in acute ischemic stroke. Determining if there is a benefit of aggressive glycemic control within the first few hours of embolic stroke warrants further study.
Abstract TP147: Relationship Between Carotid Artery Atherosclerosis and Hyoid Anatomy: Results From a Cross-sectional and Longitudinal Cohort Study
Authors: Siegler James E , Konsky Glenn , Renner Christopher , Moreno-De-Luca Andres , Gutman David , Messé Steven
Published: January 2019

Background:
Asymmetric internal carotid artery (ICA) plaque is common and are not fully explained by carotid geometry. Case reports have identified an increased risk of ICA injury and atherosclerosis with shorter hyoid wing-ICA distances. However, this relationship has not been characterized on a population level.

Hypothesis:
Shorter hyoid-ICA distances will be associated with greater ICA plaque and accelerated plaque formation over time.

Methods:
Retrospective cross-sectional and longitudinal cohort designs were used to evaluate consecutive adult patients at 3 hospitals who underwent 2 computed tomography angiography (CTA) studies of the neck ≥2 years apart (01/2000-07/2017). Patients with pre-existing neck or ICA surgery, dissection, or occlusion were excluded. Moderate ICA plaque (≥3mm), plaque characteristics, and stenosis at the level of the greater hyoid wing were compared by hyoid-ICA distance; and comparisons were made over time.

Results:
Sixty-six patients were included, with a median age of 64 years (IQR 53-73), 37 (56.1%) female, and 28 (42.4%) non-white. The median hyoid-ICA distance was 3.06mm (IQR 1.27-6.20mm), and when the hyoid-ICA distance was less than the median, moderate plaque was not more common (53.0% vs. 48.5%, p=0.601), and this remained non-significant after multivariable adjustment (OR 0.88, 95%CI 0.37-2.07, p=0.765) or when analyzed by hyoid-ICA distance quartile (adjusted p=0.586; Figure 1A). After a median follow-up of 1002 days (range 392-3,397 days), the odds of plaque progression (increase by ≥0.5mm) were not significantly greater when the hyoid-ICA distance was less than the median (adjusted OR 0.74, 95%CI 0.30-1.83, p=0.513), or when compared across distance quartiles (adjusted p=0.795; Figure 1B).

Conclusion:
In this cross-sectional and longitudinal cohort study, there was no association between hyoid wing proximity and ICA plaque thickness or stenosis.
Abstract TP148: Varicella Zoster Virus Immunoreactivity of Cerebral Vessels, Arterial Remodeling, and Cellular Inflammation
Authors: Hunter Madeleine D , Gonzalez Marco A , Mohr Jay P , Elkind Mitchell S , Marshall Randolph S , Morgello Susan , Gutierrez Jose
Published: January 2019

Background:
Though Varicella Zoster Virus (VZV) causes cerebral vasculitis and is found in vessels of those at risk for reactivation, its effect on vessel structure is unclear. We hypothesized that VZV would be associated with inward cerebral arterial remodeling and inflammation, especially in HIV.

Methods:
Large and penetrating autopsied brain arteries from cases with and without HIV (age- and sex-matched) were stained with an anti-VZV latency-associated open reading frame 63 gene product antibody to identify likely-latent VZV presence and localization in arterial layers. For each artery, we found lumen, wall, intima and interadventitial diameters and percent stenosis, using a semi-automated method with color thresholding with excellent reliability. We visually rated the presence of concentric intima thickening and/or atheromas with good to excellent reliability. We stained for CD68 to assess macrophage presence in arterial walls. We used hierarchical models, adjusting for demographics and risk factors.

Results:
66% of the 162 autopsied brains (mean age 49
+
9 years, 70% male, 56% non-white, 52% HIV+) had VZV in at least one vessel. In large arteries, VZV was associated with intima thinning similarly with and without HIV. Among those with HIV and CD4
<
200 cells/μl at death, VZV was inversely associated with intima thickness (ß= -24.22, p=0.01), interadventitial (ß= -222.80, p=0.02) and luminal diameters (ß= -186.80, p=0.03), and lumen-to-wall ratio (ß= -0.31, p=0.02). Intima VZV was associated with arterial wall CD68+ cells, and especially with intima CD68 (ß= 0.19, p=0.03). In a model stratified by HIV, VZV was associated with CD68 among those with HIV (ß=0.13, p=0.01), but not those without (ß=0.07, p=0.18).

Conclusion:
Likely-latent VZV is associated with small arteries and low lumen-to-wall ratios, especially in HIV with persistent immunosuppression. Monocytic inflammation with latent VZV may play a role in VZV- and HIV-induced brain arterial remodeling.
Abstract TP149: The Effects of Intravenous Thrombolysis on Distal Migration of Clots and Recanalization in Acute Ischemic Strokes Also Treated With Endovascular Therapies
Authors: Cobia Miles , Albright Karen C , Foreman Paul , Schmalz Phillip , Gropen Toby , Harrigan Mark
Published: January 2019

Introduction:
The role of intravenous recombinant tissue plasminogen activator (IV r-tPA) prior to endovascular therapy (ET) in acute ischemic stroke (AIS) has been heavily debated in recent literature. Understanding the direct relationship of IV r-tPA to occlusive thrombus size and migration may lead to further understanding of the potential benefits of IV r-tPA in AIS cases treated with ET.

Methods:
We retrospectively studied consecutive AIS patients who underwent a CT angiogram (CTA) followed by ET at our center from 7/2016-1/2017. We compared demographic, clinical, and imaging characteristics between subjects treated with or without IV r-tPA. Three raters, blind to IV r-tPA exposure, independently evaluated clot burden and location of each thrombus on CTA in comparison to digital subtraction angiography (DSA) images.

Results:
Among 29 patients meeting inclusion/exclusion criteria, 16 received IV r-tPA prior to ET and 13 received ET alone. Agreement among raters ranged from 0.296 (clot burden score of thrombus on DSA) to 0.800 (location of thrombus on CTA). There were no statistically significant differences in the treated and untreated groups (Table). The odds of distal migration of clot or recanalization on subsequent DSA among tPA treated patients was more than 4 times that of non-tPA treated patients (OR 4.28, 95% CI 0.71, 25.92).

Conclusion:
In summary, 43.8% of patients in the IV r-tPA plus ET treated group exhibited distal migration of a thrombus or recanalization when observed on DSA, compared to 15.4% in the ET-only group. Although our results suggest that IV r-tPA may change the size and location of the thrombus, our results were not adequately powered to detect significant differences. However, the inter-rater reliability was favorable, suggesting that this investigational technique may be successfully applied to a larger sample size in future studies investigating the role of IV r-tPA bridging therapy in AIS treated with ET.
Abstract TP152: Maternal Morbidity Outcomes in Moyamoya Syndrome in New York State
Authors: Gatollari Hajere J , Boehme Amelia K , Connolly E. Sander , Friedman Alexander M , Elkind Mitchell S , Willey Joshua Z , Miller Eliza C
Published: January 2019

Background:
Pregnancy is associated with increased stroke risk in young women. Idiopathic moyamoya syndrome (IMMS) is a rare condition characterized by progressive narrowing of large cerebral arteries resulting in flimsy collaterals prone to rupture or thrombosis. Data are limited on pregnancy outcomes in women with IMMS. We hypothesized that IMMS would be associated with increased pregnancy morbidity, including stroke.

Methods:
Using the New York State Department of Health Statewide Planning and Research Cooperative System data from 2000-2014 we identified all women aged 18 and older with diagnoses of IMMS (ICD-9 437.5) who had hospitalizations for delivery at any time either prior, concomitant or subsequent to IMMS diagnosis. We considered a pregnancy to be IMMS-exposed if it occurred ≤ 3 years prior to, or any time after, IMMS diagnosis. We defined pregnancy morbidity as admission within 1 year of delivery for any of the Center for Disease Control and Prevention’s severe maternal morbidity indicators, including stroke. We compared the morbidity of IMMS-exposed pregnancies to unexposed pregnancies occurring in the same cohort >3 years prior to IMMS diagnosis. We used conditional logistic regression to calculate odds ratio (OR) and 95% confidence intervals (95%CI), adjusting for women with both exposed and unexposed pregnancies.

Results:
We identified 134 patients with IMMS, with 117 exposed pregnancies and 147 unexposed pregnancies. Severe maternal morbidity was higher for exposed pregnancies (33.3% vs 19.0%, OR: 2.1, 95%CI: 1.2-3.7). After adjusting for maternal morbidity, exposed pregnancies had more caesarean sections (44.4% vs 23.0%, OR: 4.2, 95%CI: 2.3-7.6). Complications occurring during and after exposed pregnancies included stroke, acute myocardial infarction, cardiac arrest, cardiac arrhythmia requiring conversion, eclampsia, pulmonary edema, and adult respiratory distress syndrome.

Conclusion:
Pregnancies within 3 years prior or any time after IMMS diagnosis had increased maternal morbidity within 1 year of delivery. Prospective studies are needed to better characterize increased maternal risks for women with moyamoya syndrome and develop preventive strategies.
Abstract TP154: Characteristics and Surgical Outcome of Patients With Carotid Stenosis Resistant to Medical Therapy
Authors: Hosoda Kohkichi , Fujita Atsushi , Kohta Masaaki , Kimura Hidehito , Matsuo Kazuya , Imahori Taichiro , Nakai Tomoaki , Uozumi Yoichi , Kohmura Eiji
Published: January 2019

Background:
The recent progress of medical therapy has made the surgical indication for carotid artery stenosis more stringent. Therefore, surgical outcome of patients resistant to medical therapy were compared with those non-resistant to medical therapy.

Methods:
Between August 2006 and September 2017, 320 consecutive carotid revascularizations (CEA/CAS) were performed in our institute. Resistant (R) group was defined as patients with crescendo TIA, repeated TIA/infarction despite of medical therapy (n=15) or patients with symptomatic mobile plaque (n=5) (total 18; 2 patients overlapped). Other patients with symptomatic (116) and asymptomatic (186) stenosis were defined as non-resistant (N) group (total 302). Clinical characteristics, magnetic resonance (MR) plaque imaging, plaque pathology, and long-term outcomes with survival analysis were investigated.

Results:
13 CEA and 5 CAS were performed in R group. 181 CEA and 121 CAS were performed in N group. The periprocedural stroke & death rate was higher in R group (1/18 [5.6%]; CEA 0/13, CAS 1/5 [20%]) than in N group (9/302 [3.0%]; CEA 4/181 [2.2%], CAS 5/121 [4.1%]) but no significant difference was observed. Signal intensity ratio of plaque relative to sternocleidomastoid muscle was significantly higher in R group than in N group (1.9 vs 1.5, p = 0.007; Fig. 1A) in MR plaque imaging study, which was consistent with intraplaque hemorrhage in pathological findings of R group. Estimates of the 4-year event rate of primary end point (stroke/death/MI within 30 days, and any ipsilateral stroke thereafter) using competing risk analysis were 18% for R group and 4.5% for N group (P = 0.022; Fig. 1B). ALL recurrence occurred after CAS.

Conclusion:
The resistance to medical therapy was likely to be due to severe intraplaque hemorrhage, which might explain relatively poor outcome of CAS in R group. Appropriate indication is critical for good outcome of R group.
Abstract TP155: Comparison Between Medical Therapy and Endovascular Treatment of the Extracranial Atherosclerotic Vertebral Artery Disease: A Systematic Review
Authors: Majidi Shahram , Memon Muhammad Z , Daniel David , Del Calvo Haydee , Chen Chen , Ma Yan , Qureshi Adnan I
Published: January 2019

Objective:
To assess the potential benefit of endovascular treatment compared to medical treatment in patients with symptomatic extracranial vertebral artery (ECVA) atherosclerotic disease in terms of clinical outcomes through a systematic literature review of published reports.

Methods:
We identified ECVA studies published between January 1966 and December 2017 using a search on PubMed and Cochrane libraries supplemented by review of bibliographies of selected publications based on pre-specified criteria. The rates of stroke and stroke and/or death were estimated for best medical treatment and endovascular treatment, at 1 month and at last follow-up. A random effects model was used to calculate pooled proportions (PP) across all studies and 95% confidence intervals.

Results:
Of a total of 57 reports reviewed, 8 studies reported outcomes in patients receiving medical treatment only (362 patients) and 49 studies reported upon patients treated with endovascular approach (2142 patients). The mean age of patients in the medical group was 65.6 years (range 61.3 - 69.0 years) and 64.1 years (range 53.5 - 72 years ) in the endovascular group. The 30 day incidence of stroke was 26 (7.2%) in the medical treatment group compared to 18 (0.84%) in the endovascular group, resulting in a higher risk for patients in the best medical treatment when compared to endovascular treatment [PP 0.0559 vs. 0.0025; p-value = 0.0001)]. Similarly at follow-up, 33 (12.3 %) stroke were observed in the medical group compared to 51(2.4 %) in the endovascular group [PP 0.1027 vs. 0.0109 ; p-value = 0.0001)].There was also statistically difference in stroke related death in the medical group vs endovascular group 12 (4.5 % ) vs 1 (0.04% ) [PP 0.03309 vs. 0.0000 ;p-value =0.001] . There was no statistically significant difference in the rates of recurrent TIA or death to other causes between the two groups.

Conclusion:
Our analysis demonstrated that endovascular treatment significantly reduced the risk of stroke and death when compared to best medical treatment alone at 30 days and at follow-up. Randomized clinical trial is warranted for further understanding of the safety and efficacy of the endovascular treatment.
Abstract TP158: Risk prediction for symptomatic Intracranial Hemorrhage (sICH) in Acute Ischemic Stroke (AIS) Patients Treated With Intravenous Thrombolysis (IVT): Does Infarct Location Matter?
Authors: Bavarsad Shahripour Reza , Goyal Nitin , Tsivgoulis Georgios , Pandhi Abhi , Singh Savdeep , Malhotra Konark , Bryndziar Tomas , Sukhdeo Rena , Aboud Talal , Krishnaiah Balaji , Nearing Katherine , Alexandrov Anne W , Alexandrov Andrei V
Published: January 2019

Introduction:
There are mounting data supporting a substantially lower risk of sICH in AIS patients with posterior circulation stroke (PCS) following treatment with IVT. However, stroke location is not included in any of the numerous risk prediction scores for sICH complicating IVT in AIS. We sought to compare the safety and efficacy of IVT for AIS with respect to the location of acute cerebral ischemia in a high-volume tertiary care stroke center.

Methods:
Consecutive AIS patients treated with IVT during a five-year period were evaluated. Baseline stroke severity and early hypodensity on baseline CT were assessed by NIHSS-score and ASPECTS by certified physicians. Stroke location was classified as posterior (PCS) vs. anterior circulation (ACS), and supratentorial (STN) vs. infraterorial (ITN) infarction. Safety of IVT was evaluated using the SITS-MOST sICH definition. Three-month functional status was assessed using modified Rankin Scale (mRS) scores.

Results:
Out of total 1008 IVT-treated AIS patients [52% men, mean age 64±15years, median baseline NIHSS-score: 8 pts (IQR: 4-4)], 181 (18%) had PC and 88 (9%) had STN location. The rates of sICH were lower in patients with PCS [2.8% vs. 6.9%; p=0.039 by Fisher’s exact test (FET)] and ITN infarction (0% vs. 6.7%; p=0.005 by FET). PCS and ITN strokes (OR computed using Firth’s penalized likelihood method for rare events: 0.11; 95%CI: 0.01-1.82) were not independently associated with lower likelihood of sICH on multivariable logistic regression models adjusting for multiple potential confounders including demographics, vascular risk factors, onset-to-treatment time, baseline stroke severity, serum glucose, BP parameters and ASPECTS, pretreatment with antiplatelets (single or dual), statins and oral anticoagulants.

Conclusions:
Our study indicates that infarct location appears not to be independently related to the risk of sICH in AIS patients treated with IVT.