Stroke Size Research Articles

S100B and brain ultrasound: Novel predictors for functional outcome in acute ischemic stroke patients

ObjectiveStroke is a leading cause of mortality and disability worldwide. This study aimed to assess the prognostic value of serum S100B protein, transcranial color-coded duplex sonography (TCCD), and optic nerve sheath diameter (ONSD) in predicting functional outcomes in critically ill patients with acute ischemic stroke (AIS). MethodsIn this prospective observational study, 80 adult AIS patients were evaluated. Serum S100B protein levels, ONSD, and middle cerebral artery pulsatility index (MCA PI) were measured on days 1 and 3. Functional outcomes at 90 days were assessed using the modified Rankin Scale (mRS) and categorized into favourable (mRS 0–2) or unfavourable (mRS 3–6) groups. The association of demographic, clinical, laboratory, and imaging parameters with mRS outcomes was analyzed. ResultsPoor mRS outcomes occurred in 82.5 % of patients. Factors significantly associated with poor outcomes were female sex, higher National Institutes of Health Stroke Scale (NIHSS) scores on days 1, 3, and 7, and larger stroke size. Receiver Operating Characteristic (ROC) curve analysis revealed that ONSD at days 1 and 3, serum S100B levels at day 1, and right MCA PI at day 1 had significant predictive value for poor mRS outcome. Multivariate analysis identified female sex, S100B on day 1, and NIHSS on days 1, 3, and 7 as independent predictors of poor mRS outcomes. ConclusionsThe combination of S100B, ONSD, and MCA PI improved the prediction of functional outcomes in critically ill AIS patients. Early S100B measurement and brain ultrasound evaluation may serve as valuable prognostic tools for guiding therapeutic decision-making. This study provides novel insights into the role of S100B and brain ultrasound in stroke outcome prediction, particularly in critically ill AIS patients.

Short-term of mortality in acute stroke patients

Background: Stroke is a major cause of disability and death. A significant number of patients with acute stroke dies within 30 days of developing stroke. The aim of the study was to determine the short-termmortality (within 30 days) in acute stroke patients. Methods: This was a cross-sectional study, carried out in the Department of Medicine of Rangpur Medical College Hospital. Date was collected for 6 months (from January to June). Results: During the study period, we studied of 248 acute stroke patients, among them 110 were hemorrhagic and 138 were ischemic. Mean age of the patients were 56.02 years in hemorrhagic stroke and 61.26 years in ischemic stroke. In case of hemorrhagic stroke, short term mortality was 45.5% (50), among them in hospital death was 88% (44) and majority of the deaths occurred with in the first 7 days. Mortality was significantly higher among patients with larger hematomas (>60 cm3) compared to subjects with smaller hematomas (<30 cm3). Short term mortality was 18.1% in ischemic stroke. Infarction size more than 10 mm2, total anterior circulation syndrome (TACS) and GCS less than 10 at presentation were significantly associated with short term mortality. Conclusion: Short-term mortality was high in acute hemorrhagic stroke than acute ischemic stroke. In hemorrhagic stroke larger hematoma, GCS at presentation, ventricular extension and in case of ischemic stroke size of the infarction, arterial territory involvement and GCS were predictor of mortality. Bangladesh J Medicine 2023; Vol. 34, No. 2(1) Supplement: 205

Association between bilirubin levels and risk of stroke: a systematic review and meta-analysis

ObjectiveTo evaluate the association between bilirubin levels and stroke risk.DesignSystematic review and meta-analysis, reported in accordance with Meta-analysis Of Observational Studies in Epidemiology guidelines.Data sourcesThe PubMed, Embase, Cochrane Central Register...

An improved defocusing adaptive style transfer method based on a stroke pyramid.

Image style transfer aims to assign a specified artist's style to a real image. However, most existing methods cannot generate textures of various thicknesses due to the rich semantic information of the input image. The image loses some semantic information through style transfer with a uniform stroke size. To address the above problems, we propose an improved multi-stroke defocus adaptive style transfer framework based on a stroke pyramid, which mainly fuses various stroke sizes in the image spatial dimension to enhance the image content interpretability. We expand the receptive field of each branch and then fuse the features generated by the multiple branches based on defocus degree. Finally, we add an additional loss term to enhance the structural features of the generated image. The proposed model is trained using the Common Objects in Context (COCO) and Synthetic Depth of Field (SYNDOF) datasets, and the peak signal-to-noise ratio (PSNR) and structural similarity index (SSIM) are used to evaluate the overall quality of the output image and its structural similarity with the content image, respectively. To validate the feasibility of the proposed algorithm, we compare the average PSNR and SSIM values of the output of the modified model and those of the original model. The experimental results show that the modified model improves the PSNR and SSIM values of the outputs by 1.43 and 0.12 on average, respectively. Compared with the single-stroke style transfer method, the framework proposed in this study improves the readability of the output images with more abundant visual expression.

Abstract Number ‐ 171: Stroke location as predictor of bleeding after EVT for ischemic stroke in the anterior circulation

Introduction Hemorrhage is a known risk of Endovascular thrombectomy (EVT) for ischemic stroke . Several predictors of bleeding have been identified. However, stroke location has not yet been evaluated as an independent predictor. Methods Patients ≥ 18 years who underwent EVT for anterior circulation large vessel occlusion between January 1, 2020, and December 31, 2021, at our centre were included. After the exclusion criteria, a total of 344patients were analyzed. The admission CT scans were reviewed by a neuroradiologist to determine the ASPECTS, and classify the involved regions into location groups: only central core, only cortical, and both central and cortical areas. Post EVT images were evaluated to assign the Heidelberg bleeding classification. Statistical analysis was performed in R, version 4.1. For univariate analyses, Fisher’s exact or chi‐square test was used for categorical data. Quantitative data were tested for normality, and the t‐test or Mann‐Whitney test was applied accordingly. All variables in the univariate analyses with p < 0.15 were considered for the stepwise logistic regression models. Results Patients had a median age of 73 years (IQR 20), NIHSS of 16 (IQR 9),ASPECTS of 7 (IQR 3), systolic blood pressure of 146 mmHg (IQR 25), and glycemia of 7 mmol/L (IQR 2). The most frequent occlusion site was M1 (65.7%), and most patients had an mTICI > 2A (89.5%). Bleeding occurred in 182 (52.9%) and intraparenchymal hematoma in 73 (21.2%) patients, with most bleeding only in the central core (65.4%), with the lentiform nucleus involved in 122 (67%) of the bleeds. Thirty‐eight patients died (11%), and 237 had a modified Rankin score > 2 at discharge (68.9%). Stroke location was significant for all types of bleeding (p < 0.001) and intraparenchymal hematoma (p = 0.137) in the univariate analyses. However, after multiple logistic regression, the stroke location was not an independent predictor of any type of bleeding. On the other hand, a lower ASPECTS was a significant predictor of all types of bleeding (p < 0.001; OR 1.347; 95% CI 1.1799 ‐ 1.539) and intraparenchymal hematoma (p = 0.009; OR 1.756; 95% CI 1.152 ‐ 2.677). In addition to ASPECTS, high NIHSS (p = 0.038; OR 1.058; 95% CI 1.003 ‐ 1.115) was a significant predictor of all types of bleeding, while high systolic blood pressure (p = 0.027; OR 1. 037;95% CI 1.004 ‐ 1.071), cardioembolic stroke (p = 0.042; OR 10.408; 95% CI 1.085 ‐ 99.889), and poor collaterals (p = 0.046; OR 5.068; 95% CI 1.029 ‐ 24.951) were significant for intraparenchymal hematoma. Conclusions Stroke location is not an independent predictor of bleeding. However, stroke size, as indicated by the ASPECT, is a predictor of bleeding after EVT. Moreover, some modifiable predictors were not significant because they are already controlled for in the study, but systolic pressure was a significant predictor of intraparenchymal hematoma and shows that more studies are needed to determine the appropriate control levels to reduce the chance of bleeding without compromising cerebral perfusion.

SAN-Net: Learning generalization to unseen sites for stroke lesion segmentation with self-adaptive normalization

There are considerable interests in automatic stroke lesion segmentation on magnetic resonance (MR) images in the medical imaging field, as stroke is an important cerebrovascular disease. Although deep learning-based models have been proposed for this task, generalizing these models to unseen sites is difficult due to not only the large inter-site discrepancy among different scanners, imaging protocols, and populations, but also the variations in stroke lesion shape, size, and location. To tackle this issue, we introduce a self-adaptive normalization network, termed SAN-Net, to achieve adaptive generalization on unseen sites for stroke lesion segmentation. Motivated by traditional z-score normalization and dynamic network, we devise a masked adaptive instance normalization (MAIN) to minimize inter-site discrepancies, which standardizes input MR images from different sites into a site-unrelated style by dynamically learning affine parameters from the input; i.e., MAIN can affinely transform the intensity values. Then, we leverage a gradient reversal layer to force the U-net encoder to learn site-invariant representation with a site classifier, which further improves the model generalization in conjunction with MAIN. Finally, inspired by the “pseudosymmetry” of the human brain, we introduce a simple yet effective data augmentation technique, termed symmetry-inspired data augmentation (SIDA), that can be embedded within SAN-Net to double the sample size while halving memory consumption. Experimental results on the benchmark Anatomical Tracings of Lesions After Stroke (ATLAS) v1.2 dataset, which includes MR images from 9 different sites, demonstrate that under the “leave-one-site-out” setting, the proposed SAN-Net outperforms recently published methods in terms of quantitative metrics and qualitative comparisons.

Cardioprotective Effects of a Selective c-Jun N-terminal Kinase Inhibitor in a Rat Model of Myocardial Infarction.

Activation of c-Jun N-terminal kinases (JNKs) is involved in myocardial injury, left ventricular remodeling (LV), and heart failure (HF) after myocardial infarction (MI). The aim of this research was to evaluate the effects of a selective JNK inhibitor, 11H-indeno [1,2-b]quinoxalin-11-one oxime (IQ-1), on myocardial injury and acute myocardial ischemia/reperfusion (I/R) in adult male Wistar rats. Intraperitoneal administration of IQ-1 (25 mg/kg daily for 5 days) resulted in a significant decrease in myocardial infarct size on day 5 after MI. On day 60 after MI, a significant (2.6-fold) decrease in LV scar size, a 2.2-fold decrease in the size of the LV cavity, a 2.9-fold decrease in the area of mature connective tissue, and a 1.7-fold decrease in connective tissue in the interventricular septum were observed compared with the control group. The improved contractile function of the heart resulted in a significant (33%) increase in stroke size, a 40% increase in cardiac output, a 12% increase in LV systolic pressure, a 28% increase in the LV maximum rate of pressure rise, a 45% increase in the LV maximum rate of pressure drop, a 29% increase in the contractility index, a 14% increase in aortic pressure, a 2.7-fold decrease in LV end-diastolic pressure, and a 4.2-fold decrease in LV minimum pressure. We conclude that IQ-1 has cardioprotective activity and reduces the severity of HF after MI.

Abstract TP156: Neurological Outcomes After Perinatal Stroke: A Single Center Cohort Study

Introduction: Neurological outcomes in pediatric stroke survivors have been described in observational studies. The Pediatric Stroke Outcome Measures (PSOM) was the first tool validated in children to describe outcomes specifically in stroke (Kitchen et al, 2012). Patients diagnosed with a perinatal stroke comprised 24% of this cohort, while the remainder of patients had suffered from a childhood stroke. Most patients (~ 65%) had no or mild neurological deficits after 5 years of follow-up, represented with a total PSOM score of 0-1. We examined whether perinatal stroke patients would have similar trajectories to the outcomes previously described in pediatric stroke that occurred beyond the perinatal period. Methods: We conducted a retrospective review of our pediatric stroke database at Massachusetts General Hospital. Perinatal stroke survivors were identified, and data extracted from longitudinal follow-up clinic visits. PSOM scores were acquired at: discharge, visits between 2-4 years, 5-7 years, and beyond 7 years. Results: Patients who had endured a perinatal stroke with subsequent PSOM measures recorded were identified (N= 78). Neuroimaging was obtained in the neonatal period (n = 50) or at initial clinical presentation (n = 28; presumed perinatal stroke). Preliminary analyses show that perinatal stroke patients trended towards having increased PSOM scores over extended follow-up beyond 7 years from the index clinical encounter. Discussion: Interval monitoring will unmask deficits throughout development for perinatal stroke patients and can trend towards accrual of further neurological disability. This is in contrast with prior cohorts of childhood stroke where most patients endured stroke beyond the perinatal period and had total PSOM scores of 0-1 beyond 5 years of follow up. Further analyses are underway to establish effect of stroke mechanism, size, and laterality. Separate analyses to map lesion topography to structural and functional network disruptions that occur after perinatal stroke will be performed. Understanding the relationship between these disruptions and functional outcomes will aid in deficit prediction and trajectory modelling, to guide individualized interventions for the youngest of stroke survivors.

Baseline Function and Rehabilitation Are as Important as Stroke Severity as Long-term Predictors of Cognitive Performance Post-stroke.

Although individuals with low stroke severity tend to recover well, cognitive impairment is common independent of stroke size or location. In this study, the patterns of recovery for individual cognitive domains and factors associated with outcome were examined. A prospectively enrolled cohort of patients with minor stroke was administered cognitive testing at 1, 6, and 12 mos postinfarct. Composite T scores were generated for global cognition and well as independent cognitive domains at each time point. Paired t tests compared changes in scores over time. Regression models identified factors associated with improvement. A total of 46 patients, with an average NIH Stroke Scale score of 2.7, were enrolled. Average age was 61.3 yrs. Patients improved overall between 1 and 6 mos; however, distinct patterns of recovery were seen for different cognitive domains. The most significant improvement was in spatial memory. Verbal memory scores remained low longitudinally. Motor speed and executive function increased, then plateaued. Despite a mean education of 13.6 yrs, only 36% of global cognition scores were higher than or equal to the normative mean at 12 mos, and only 57% of patients improved their global scores from 6 to 12 mos. Late recovery was associated with lower NIH Stroke Scale scores, higher 1-mo Montreal Cognitive Assessment scores, and rehabilitation. Baseline function predicted overall long-term recovery. Patterns of recovery are distinct for individual cognitive domains for patients with minor stroke. Stroke severity and rehabilitation influence trajectory. Premorbid baseline predicts long-term outcome.

DMHC: Device-free multi-modal handwritten character recognition system with acoustic signal

Efficient typing in a mobile device is a long-standing problem because of its small-size touch screen. Methods for contactless solutions using acoustic sensors have been proposed recently, which are device-free and low cost. However, these methods are not practical enough as they use either the microphone of the mobile device for recording the sounds generated during writing or the speaker of the device for playing a frequency modulated ultrasonic signal and then the signal reflected from the hand of the user is analyzed, where the former process requires a quiet environment and the latter process requires the user to write a letter in a single stroke and large size. In order to overcome those challenges, we present DMHC, which is an effective and device-free multi-modal handwritten character recognition system. DMHC fuses two different acoustic modalities, which are ultrasonic and general audio signals. The main feature of DMHC is that we extract the latent interactions between the ultrasonic and general acoustic signals. Specifically, DMHC implements the noise-resistant handwritten character recognition system for reliably recognizing handwritten characters in real life. We implement our proposed module based on the self-attention method to multiple channel fusion. Extensive experimental results demonstrate the effectiveness and robustness of DMHC under various conditions, where the recognition accuracies of letters and words are found to be 97.4% and 95.3%, respectively.

Abstract 10017: Which Thrombi at the Apex of the Left Ventricle Were More Prone for Embolization and Stroke?

Introduction: Patients with apical thrombus due to anterior wall ST segment Elevation Myocardial Infarction (AWMI) or dilated cardiomyopathy (DilCM) have high risk of emboli, including stroke. Hypothesis: Which factor of a thrombus at the apex of the left ventricle makes it vulnerable for or resistant to embolization? Is it its loose (or well organized) tissue formation as a fresh (or old) thrombus so it disintegrates quickly (or stays resistant) and becomes vulnerable for (or less prone to) embolization? Methods: Patients with AWMI or DilCM with apical thrombus by echo were consecutively enrolled. Patients with atrial fibrillation were excluded. The data to be collected included: (1) Time of discovery of apical thrombi by echo to time of stroke (2) result of treatment (thrombolysis with long term vit K antagonists vs novel oral anticoagulants (NOACs) and (3) pattern of recovery. Results: From 2010-2021, there were 32 patients identified with apical thrombus. 12 patients due to AWMI and 20 patients due to Dil CM. 3 AWMI patients developed stroke (25%) within a mean of 7.5 days after discovery while only 2 patients with Dil CM had stroke (10%) 21 days after discovery (p<0.05). At the time of stroke, all apical thrombi of AWMI patients were small, of round shape, protruding out and of heterogenous consistency (mixed black and white intensity on echo). The patients responded well to thrombolysis and recovered near completely. While for patients with Dil CM, all apical thrombi were moderately large, of flat surface incorporating into the contour of the apex, non-protruding and of homogenous consistency. When these patients had stroke, the size of stroke was large and more resistant to thrombolysis. Their recovery was slow with a lot of deficits. Conclusions: For apical thrombi from AWMI, the thrombi were fresh so they disintegrated quickly and could cause more stroke however because of their smaller size and loose consistency, the recovery was more complete. The apical thrombi from Dil CM were more organized so they dissolved more slowly, caused less stroke however they were more resistant to thrombolysis. Their recovery was more limited. Larger database needs to confirm the above findings and their clinical implications.

Molecular imaging of the brain–heart axis provides insights into cardiac dysfunction after cerebral ischemia

Ischemic stroke imparts elevated risk of heart failure though the underlying mechanisms remain poorly described. We aimed to characterize the influence of cerebral ischemic injury on cardiac function using multimodality molecular imaging to investigate brain and cardiac morphology and tissue inflammation in two mouse models of variable stroke severity. Transient middle cerebral artery occlusion (MCAo) generated extensive stroke damage (56.31 ± 40.39 mm3). Positron emission tomography imaging of inflammation targeting the mitochondrial translocator protein (TSPO) revealed localized neuroinflammation at 7 days after stroke compared to sham (3.8 ± 0.8 vs 2.6 ± 0.7 %ID/g max, p < 0.001). By contrast, parenchyma topical application of vasoconstrictor endothelin-1 did not generate significant stroke damage or neuroinflammatory cell activity. MCAo evoked a modest reduction in left ventricle ejection fraction at both 1 weeks and 3 weeks after stroke (LVEF at 3 weeks: 54.3 ± 5.7 vs 66.1 ± 3.5%, p < 0.001). This contractile impairment was paralleled by elevated cardiac TSPO PET signal compared to sham (8.6 ± 2.4 vs 5.8 ± 0.7%ID/g, p = 0.022), but was independent of leukocyte infiltration defined by flow cytometry. Stroke size correlated with severity of cardiac dysfunction (r = 0.590, p = 0.008). Statistical parametric mapping identified a direct association between neuroinflammation at 7 days in a cluster of voxels including the insular cortex and reduced ejection fraction (ρ = − 0.396, p = 0.027). Suppression of microglia led to lower TSPO signal at 7 days which correlated with spared late cardiac function after MCAo (r = − 0.759, p = 0.029). Regional neuroinflammation early after cerebral ischemia influences subsequent cardiac dysfunction. Total body TSPO PET enables monitoring of neuroinflammation, providing insights into brain–heart inter-organ communication and may guide therapeutic intervention to spare cardiac function post-stroke.

Single-Center Description of Therapeutic Anticoagulation Practices and Outcomes in Large Hemispheric Infarctions.

Large hemispheric infarctions (LHIs) are associated with significant morbidity and mortality, with limited data on therapeutic anticoagulation (AC) management. We provide a descriptive analysis of the type of therapeutic AC used, the timing of introduction, rate of of radiographic vs symptomatic hemorrhagic transformation (HT), and patient outcomes. This was a retrospective review of patients with acute ischemic stroke admitted to the Neurosciences intensive care unit at a tertiary care center from January 2012 to December 2018. Inclusion criteria included admission imaging with stroke size ≥ two-thirds of the middle cerebral artery territory, ± other vascular territory, and need for therapeutic AC. HT categories included hemorrhagic infarction types 1 and 2 and parenchymal hematoma types 1 and 2. The primary outcome included HT with and without an associated clinical change. Secondary outcomes included disposition at discharge and modified Rankin Scale (mRS) score at discharge and at follow-up when available. A total of 2,317 patients were screened, 380 met the inclusion criteria for LHI, and 105 received AC. The mean age was 64 years (SD 16.8), and 50% (n = 53) were female. The mean admission NIH Stroke Scale score was 20 (SD 5.9). The mean poststroke timing to initiation of AC was 17 days (SD 10.1) (median 14 [interquartile range 10-19 days]). Indications for AC included atrial fibrillation (51%), cardiac thrombus (19%), venous thromboembolism (19%), and other (10%). Heparin was most commonly used in the very early (≤7 days) group (n = 11, 79%), whereas vitamin K antagonists without a bridge were the most commonly used among the entire cohort (n = 54, 51%). Radiographic HT was seen in 68 patients (65%) before AC initiation. After initiation of AC, 70 patients had repeat imaging, with 6 cases (6%) of worsening radiographic HT and 4 cases (4%) of symptomatic deterioration, of which 3 required reversal of AC. At discharge, 7 patients (7%) had a good outcome (mRS score 0-2). Although radiographic HT is common among patients with LHI, it does not always portend symptomatic clinical deterioration. Further research regarding AC timing and safety is necessary.

Blocking P2X7 by intracerebroventricular injection of P2X7-specific nanobodies reduces stroke lesions

BackgroundPrevious studies have demonstrated that purinergic receptors could be therapeutic targets to modulate the inflammatory response in multiple models of brain diseases. However, tools for the selective and efficient targeting of these receptors are lacking. The development of new P2X7-specific nanobodies (nbs) has enabled us to effectively block the P2X7 channel.MethodsTemporary middle cerebral artery occlusion (tMCAO) in wild-type (wt) and P2X7 transgenic (tg) mice was used to model ischemic stroke. Adenosine triphosphate (ATP) release was assessed in transgenic ATP sensor mice. Stroke size was measured after P2X7-specific nbs were injected intravenously (iv) and intracerebroventricularly (icv) directly before tMCAO surgery. In vitro cultured microglia were used to investigate calcium influx, pore formation via 4,6-diamidino-2-phenylindole (DAPI) uptake, caspase 1 activation and interleukin (IL)-1β release after incubation with the P2X7-specific nbs.ResultsTransgenic ATP sensor mice showed an increase in ATP release in the ischemic hemisphere compared to the contralateral hemisphere or the sham-treated mice up to 24 h after stroke. P2X7-overexpressing mice had a significantly greater stroke size 24 h after tMCAO surgery. In vitro experiments with primary microglial cells demonstrated that P2X7-specific nbs could inhibit ATP-triggered calcium influx and the formation of membrane pores, as measured by Fluo4 fluorescence or DAPI uptake. In microglia, we found lower caspase 1 activity and subsequently lower IL-1β release after P2X7-specific nb treatment. The intravenous injection of P2X7-specific nbs compared to isotype controls before tMCAO surgery did not result in a smaller stroke size. As demonstrated by fluorescence-activated cell sorting (FACS), after stroke, iv injected nbs bound to brain-infiltrated macrophages but not to brain resident microglia, indicating insufficient crossing of the blood–brain barrier of the nbs. Therefore, we directly icv injected the P2X7-specific nbs or the isotype nbs. After icv injection of 30 µg of P2X7 specific nbs, P2X7 specific nbs bound sufficiently to microglia and reduced stroke size.ConclusionMechanistically, we can show that there is a substantial increase of ATP locally after stroke and that blockage of the ATP receptor P2X7 by icv injected P2X7-specific nbs can reduce ischemic tissue damage.

Neurological and Functional Outcomes after Pediatric Stroke

Pediatric stroke results in life-long morbidity for many patients, but the outcomes can vary depending on factors such as age of injury, or mechanism, size, and location of stroke. In this review, we summarize the current understanding of outcomes in different neurological domains (eg, motor, cognitive, language) for children with stroke of different mechanisms (ie, arterial ischemic stroke, cerebral sinus venous thrombosis, and hemorrhagic stroke), but with a focus on World Health Organization International Classification for Functioning, Disability, and Health (ICF-CY) framework for measuring health and disability for children and youth. We describe outcomes for the population as a whole and certain factors that may further refine prognostication.

Platelet Endothelial Cell Adhesion Molecule (PECAM/CD31) Blockade Modulates Neutrophil Recruitment Patterns and Reduces Infarct Size in Experimental Ischemic Stroke

The infiltration of polymorphonuclear leukocytes (PMNs) in ischemia-reperfusion injury (I/RI) has been implicated as a critical component of inflammatory damage following ischemic stroke. However, successful blockade of PMN transendothelial migration (TEM) in preclinical studies has not translated to meaningful clinical outcomes. To investigate this further, leukocyte infiltration patterns were quantified, and these patterns were modulated by blocking platelet endothelial cell adhesion molecule-1 (PECAM), a key regulator of TEM. LysM-eGFP mice and microscopy were used to visualize all myeloid leukocyte recruitment following ischemia/reperfusion. Visual examination showed heterogeneous leukocyte distribution across the infarct at both 24 and 72 hours after I/RI. A semiautomated process was designed to precisely map PMN position across brain sections. Treatment with PECAM function-blocking antibodies did not significantly affect total leukocyte recruitment but did alter their distribution, with more observed at the cortex at both early and later time points (24 hours: 89% PECAM blocked vs. 72% control; 72 hours: 69% PECAM blocked vs. 51% control). This correlated with a decrease in infarct volume. These findings suggest that TEM, in the setting of I/RI in the cerebrovasculature, occurs primarily at the cortical surface. The reduction of stroke size with PECAM blockade suggests that infiltrating PMNs may exacerbate I/RI and indicate the potential therapeutic benefit of regulating the timing and pattern of leukocyte infiltration after stroke.

Towards Ultra-Resolution Neural Style Transfer via Thumbnail Instance Normalization

We present an extremely simple Ultra-Resolution Style Transfer framework, termed URST, to flexibly process arbitrary high-resolution images (e.g., 10000x10000 pixels) style transfer for the first time. Most of the existing state-of-the-art methods would fall short due to massive memory cost and small stroke size when processing ultra-high resolution images. URST completely avoids the memory problem caused by ultra-high resolution images by (1) dividing the image into small patches and (2) performing patch-wise style transfer with a novel Thumbnail Instance Normalization (TIN). Specifically, TIN can extract thumbnail features' normalization statistics and apply them to small patches, ensuring the style consistency among different patches. Overall, the URST framework has three merits compared to prior arts. (1) We divide input image into small patches and adopt TIN, successfully transferring image style with arbitrary high-resolution. (2) Experiments show that our URST surpasses existing SOTA methods on ultra-high resolution images benefiting from the effectiveness of the proposed stroke perceptual loss in enlarging the stroke size. (3) Our URST can be easily plugged into most existing style transfer methods and directly improve their performance even without training. Code is available at https://git.io/URST.

Controlling strokes in fast neural style transfer using content transforms

Fast style transfer methods have recently gained popularity in art-related applications as they make a generalized real-time stylization of images practicable. However, they are mostly limited to one-shot stylizations concerning the interactive adjustment of style elements. In particular, the expressive control over stroke sizes or stroke orientations remains an open challenge. To this end, we propose a novel stroke-adjustable fast style transfer network that enables simultaneous control over the stroke size and intensity, and allows a wider range of expressive editing than current approaches by utilizing the scale-variance of convolutional neural networks. Furthermore, we introduce a network-agnostic approach for style-element editing by applying reversible input transformations that can adjust strokes in the stylized output. At this, stroke orientations can be adjusted, and warping-based effects can be applied to stylistic elements, such as swirls or waves. To demonstrate the real-world applicability of our approach, we present StyleTune, a mobile app for interactive editing of neural style transfers at multiple levels of control. Our app allows stroke adjustments on a global and local level. It furthermore implements an on-device patch-based upsampling step that enables users to achieve results with high output fidelity and resolutions of more than 20 megapixels. Our approach allows users to art-direct their creations and achieve results that are not possible with current style transfer applications.

CRel and Wnt5a/Frizzled 5 Receptor-Mediated Inflammatory Regulation Reveal Novel Neuroprotectin D1 Targets for Neuroprotection

Wnt5a triggers inflammatory responses and damage via NFkB/p65 in retinal pigment epithelial (RPE) cells undergoing uncompensated oxidative stress (UOS) and in experimental ischemic stroke. We found that Wnt5a-Clathrin-mediated uptake leads to NFkB/p65 activation and that Wnt5a is secreted in an exosome-independent fashion. We uncovered that docosahexaenoic acid (DHA) and its derivative, Neuroprotectin D1 (NPD1), upregulate c-Rel expression that, as a result, blunts Wnt5a abundance by competing with NFkB/p65 on the Wnt5a promoter A. Wnt5a increases in ischemic stroke penumbra and blood, while DHA reduces Wnt5a abundance with concomitant neuroprotection. Peptide inhibitor of Wnt5a binding, Box5, is also neuroprotective. DHA-decreased Wnt5a expression is concurrent with a drop in NFkB-driven inflammatory cytokine expression, revealing mechanisms after stroke, as in RPE cells exposed to UOS. Limiting the Wnt5a activity via Box5 reduces stroke size, suggesting neuroprotection pertinent to onset and progression of retinal degenerations and stroke consequences.Graphical NPD1 disrupts Wnt5a feedback loop at two sites: (1) decreasing FZD5, thus Wnt5a internalization, and (2) by enhancing cREL activity, which competes with p65/NFkB downstream endocytosis. As a result, Wnt5a expression is reduced, and so is its inflammatory signaling in RPE cells and neurons in ischemic stroke.

Nt5e deficiency does not affect post-stroke inflammation and lesion size in a murine ischemia/reperfusion stroke model

SummaryExtracellular ATP released to the ischemic brain parenchyma is quickly metabolized by ectonucleotidases. Among them, the ecto-5′-nucleotidase CD73 encoded by Nt5e generates immunosuppressive adenosine. Genetic deletion of Nt5e led to increased infarct size in the murine photothrombotic stroke model. We aimed at validating this result using the transient middle cerebral artery occlusion (tMCAO) stroke model that represents pathophysiological aspects of penumbra and reperfusion. Three days after tMACO, we did not detect a difference in stroke size between CD73-deficient (CD73−/−) and control mice. Consistent with this finding, CD73−/− and control mice showed comparable numbers and composition of brain-infiltrating leukocytes measured by flow cytometry. Using NanoString technology, we further demonstrated that CD73−/− and control mice do not differ regarding glia cell gene expression profiles. Our findings highlight the potential impact of stroke models on study outcome and the need for cross-validation of originally promising immunomodulatory candidates.