Abstract WP317: Neutrophil Subtypes and Nets Changes in Diabetes With Acute Ischemic Stroke

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Sanxin Liu ◽  
Wei Cai ◽  
Mengyan Hu ◽  
Zhengqi Lu
Keyword(s):  
Flow Cytometry ◽  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Neutrophil Count ◽  
Neurological Deficit ◽  
Infarct Volume ◽  
Immunofluorescence Staining ◽  
Neurological Deficit Score ◽  
Immunological Mechanisms ◽  
The Brain

Objective: Ischemic stroke (AIS) is a globally high-risk cerebrovascular disease. Diabetes can aggravate ischemic stroke, while its mechanism is still unknown, Neutrophils are the first peripheral immune cells that break through the blood-brain barrier and infiltrate the brain after AIS. They have two polarization states of N1 and N2 subtypes. N1 subtype neutrophils can release neutrophil extracellular traps (NETs) containing a large number of pro-inflammatory factors and exacerbate the neuroinflammatory response. This study will explore the immunological mechanisms of diabetes exacerbating ischemic stroke. Methods: Patients with acute ischemic stroke who were admitted to hospital from Jan 2012 to Dec 2018 were collected, compared blood neutrophil count and neutrophil/lymphocyte ratio in diabetic and non-diabetic AIS patients at 1 day; Middle cerebral artery infarction (MCAO) mice was used for animal model of AIS, high-fat diet and STZ-induced type 2 diabetes model. The neurological deficit score, TTC staining, flow cytometry and immunofluorescence staining were used to observe the infarct volume, neutrophil subtypes and NETs changes between AIS with and without diabetes. Results: The neutrophil count of AIS patients with diabetes was higher than that of non-diabetic AIS patients. Animal experiments found that AIS with diabetes increase neurological deficit score and infarct volume. Flow cytometry and immunofluorescence staining found that AIS with diabetes mice can promote neutrophils infiltration into the brain and promote the polarization of neutrophils to N1 subtype and increase NETs formation. Conclusion: Diabetes can promote the neutrophil polarization of N1 subtype which leads to increased NETs formation and exacerbate ischemic stroke.

scholarly journals High blood glutamate oxaloacetate transaminase levels are associated with good functional outcome in acute ischemic stroke

2011 ◽  
Vol 31 (6) ◽  
pp. 1387-1393 ◽  
Author(s):  
Francisco Campos ◽  
Tomás Sobrino ◽  
Pedro Ramos-Cabrer ◽  
Mar Castellanos ◽  
Miguel Blanco ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Clinical Outcome ◽  
Acute Ischemic Stroke ◽  
Functional Outcome ◽  
Infarct Volume ◽  
Experimental Models ◽  
Glutamate Oxaloacetate Transaminase ◽  
Beneficial Effects ◽  
Time Of Admission ◽  
The Brain

The capacity of the blood enzyme glutamate oxaloacetate transaminase (GOT) to remove glutamate from the brain by means of blood glutamate degradation has been shown in experimental models to be an efficient and novel neuroprotective tool against ischemic stroke; however, the beneficial effects of this enzyme should be tested in patients with stroke to validate these results. This study aims to investigate the association of GOT levels in blood with clinical outcome in patients with acute ischemic stroke. In two clinical independent studies, we found that patients with poor outcome show higher glutamate and lower GOT levels in blood at the time of admission. Lower GOT levels and higher glutamate levels were independently associated with poorer functional outcome at 3 months and higher infarct volume. These findings show a clear association between high blood glutamate levels and worse outcome and vice versa for GOT, presumably explained by the capacity of this enzyme to metabolize blood glutamate.

scholarly journals Three-dimensional cultured mesenchymal stem cells enhance repair of ischemic stroke through inhibition of microglia

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yuejiao Li ◽  
Yankai Dong ◽  
Ye Ran ◽  
Yanan Zhang ◽  
Boyao Wu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Ischemic Stroke ◽  
Proinflammatory Cytokines ◽  
Infarct Volume ◽  
Brain Lesion ◽  
Three Dimensional ◽  
Artery Occlusion ◽  
Rna Seq ◽  
The Brain

Abstract Background We show previously that three-dimensional (3D) spheroid cultured mesenchymal stem cells (MSCs) exhibit reduced cell size thus devoid of lung entrapment following intravenous (IV) infusion. In this study, we determined the therapeutic effect of 3D-cultured MSCs on ischemic stroke and investigated the mechanisms involved. Methods Rats underwent middle cerebral artery occlusion (MCAO) and reperfusion. 1 × 106 of 3D- or 2D-cultured MSCs, which were pre-labeled with GFP, were injected through the tail vain three and seven days after MCAO. Two days after infusion, MSC engraftment into the ischemic brain tissues was assessed by histological analysis for GFP-expressing cells, and infarct volume was determined by MRI. Microglia in the lesion were sorted and subjected to gene expressional analysis by RNA-seq. Results We found that infusion of 3D-cultured MSCs significantly reduced the infarct volume of the brain with increased engraftment of the cells into the ischemic tissue, compared to 2D-cultured MSCs. Accordingly, in the brain lesion of 3D MSC-treated animals, there were significantly reduced numbers of amoeboid microglia and decreased levels of proinflammatory cytokines, indicating attenuated activation of the microglia. RNA-seq of microglia derived from the lesions suggested that 3D-cultured MSCs decreased the response of microglia to the ischemic insult. Interestingly, we observed a decreased expression of mincle, a damage-associated molecular patterns (DAMPs) receptor, which induces the production of proinflammatory cytokines, suggestive of a potential mechanism in 3D MSC-mediated enhanced repair to ischemic stroke. Conclusions Our data indicate that 3D-cultured MSCs exhibit enhanced repair to ischemic stroke, probably through a suppression to ischemia-induced microglial activation.

scholarly journals Cerebral endothelial cell-derived small extracellular vesicles enhance neurovascular function and neurological recovery in rat acute ischemic stroke models of mechanical thrombectomy and embolic stroke treatment with tPA

2021 ◽  
pp. 0271678X2199298
Author(s):  
Chao Li ◽  
Chunyang Wang ◽  
Yi Zhang ◽  
Owais K Alsrouji ◽  
Alex B Chebl ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Extracellular Vesicles ◽  
Mechanical Thrombectomy ◽  
Infarct Volume ◽  
Artery Occlusion ◽  
Therapeutic Effects ◽  
Vessel Occlusion ◽  
Healthy Human ◽  
Stroke Treatment

Treatment of patients with cerebral large vessel occlusion with thrombectomy and tissue plasminogen activator (tPA) leads to incomplete reperfusion. Using rat models of embolic and transient middle cerebral artery occlusion (eMCAO and tMCAO), we investigated the effect on stroke outcomes of small extracellular vesicles (sEVs) derived from rat cerebral endothelial cells (CEC-sEVs) in combination with tPA (CEC-sEVs/tPA) as a treatment of eMCAO and tMCAO in rat. The effect of sEVs derived from clots acquired from patients who had undergone mechanical thrombectomy on healthy human CEC permeability was also evaluated. CEC-sEVs/tPA administered 4 h after eMCAO reduced infarct volume by ∼36%, increased recanalization of the occluded MCA, enhanced cerebral blood flow (CBF), and reduced blood-brain barrier (BBB) leakage. Treatment with CEC-sEVs given upon reperfusion after 2 h tMCAO significantly reduced infarct volume by ∼43%, and neurological outcomes were improved in both CEC-sEVs treated models. CEC-sEVs/tPA reduced a network of microRNAs (miRs) and proteins that mediate thrombosis, coagulation, and inflammation. Patient-clot derived sEVs increased CEC permeability, which was reduced by CEC-sEVs. CEC-sEV mediated suppression of a network of pro-thrombotic, -coagulant, and -inflammatory miRs and proteins likely contribute to therapeutic effects. Thus, CEC-sEVs have a therapeutic effect on acute ischemic stroke by reducing neurovascular damage.

Abstract P538: A Detailed Analysis of Intracranial Hemorrhage After Endovascular Treatment in Acute Ischemic Stroke Due to Large Vessel Occlusion in the Escape-NA1 Trial

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Johanna Ospel ◽  
Michael D Hill ◽  
Nima Kashani ◽  
Arnuv Mayank ◽  
Nishita Singh ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Intracranial Hemorrhage ◽  
Intraventricular Hemorrhage ◽  
Infarct Volume ◽  
Prognostic Impact ◽  
Vessel Occlusion ◽  
Good Outcome

Purpose: We investigated the prevalence and prognostic impact on outcome of any intracranial hemorrhage, hemorrhage morphology, type and volume in acute ischemic stroke patients undergoing mechanical thrombectomy. Methods: Prevalence of intracranial hemorrhage, hemorrhage type, morphology and volume was determined on 24h follow-up imaging (non contrast head CT or gradient-echo/susceptibility-weighted MRI). Proportions of good outcome (mRS 0-2 at 90 days) were reported for patients with vs. without any intracranial hemorrhage. Multivariable logistic regression with adjustment for key minimization variables and total infarct volume was performed to obtain adjusted effect size estimates for hemorrhage type and volume on good outcome. Results: Hemorrhage on follow up-imaging was seen in 372/1097 (33.9%) patients, among them 126 (33.9%) with hemorrhagic infarction (HI) type 1, 108 (29.0%) with HI-2, 72 /19.4%) with parenchymal hematoma (PH) type 1, 37 (10.0) with PH2, 8 (2.2%) with remote PH and 21 (5.7%) with extra-parenchymal/intraventricular hemorrhage. Good outcomes were less often achieved by patients with hemorrhage on follow-up imaging (164/369 [44.4%] vs. 500/720 [69.4%]). Any type of intracranial hemorrhage was strongly associated with decreased chances of good outcome ( adj OR 0.62 [CI 95 0.44 - 0.87]). The effect of hemorrhage was driven by both PH hemorrhage sub-type [PH-1 ( adj OR 0.39 [CI 95 0.21 - 0.72]), PH-2 ( adj OR 0.15 [CI 95 0.05 - 0.50])] and extra-parenchymal/intraventricular hemorrhage ( adj OR 0.60 (0.20-1.78) Petechial hemorrhages (HI-1 and HI-2) were not associated with poorer outcomes. Hemorrhage volume ( adj OR 0.97 [CI 95 0.05 - 0.99] per ml increase) was significantly associated with decreased chances of good outcome. Conclusion: Presence of any hemorrhage on follow-up imaging was seen in one third of patients and strongly associated with decreased chances of good outcome.

Abstract MP16: Excessive White Matter Hyperintensity Burden and Functional Outcomes After Acute Ischemic Stroke

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Sungmin Hong ◽  
Anne-katrin Giese ◽  
Markus D Schirmer ◽  
Adrian V Dalca ◽  
Anna Bonkhoff ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
White Matter ◽  
Acute Ischemic Stroke ◽  
Functional Outcomes ◽  
Life Time ◽  
Stroke Recovery ◽  
White Matter Hyperintensity ◽  
Brain Health ◽  
Stroke Outcomes ◽  
The Brain

Objective: Ability of the brain to recover after an acute ischemic stroke (AIS) is linked to the pre-stroke burden of white matter hyperintensity (WMH), a radiographic marker of brain health. We sought to determine the excessive WMH burden in an AIS population and investigate its association with 3-month stroke outcomes. Data: We used 2,435 subjects from the MRI-GENIE study. Three-month functional outcomes of 872 subjects among those subjects were measured by 90-day modified Ranking Scale (mRS). Methods: We automatically quantified WMH volume (WMHv) on FLAIR images and adjusted for a brain volume. We modeled a trend using the factor analysis (FA) log-linear regression using age, sex, atrial fibrillation, diabetes, hypertension, coronary artery disease and smoking as input variables. We categorized three WMH burden groups based on the conditional probability given by the model (LOW: lower 33%, MED: middle 34%, and HIGH: upper 33%). The subgroups were compared with respect to mRS (median and dichotomized odds ratio (OR) (good/poor: mRS 0-2/3-6)). Results: Five FA components out of seven with significant relationship to WMHv (p<0.001) were used for the regression modeling (R 2 =0.359). The HIGH group showed higher median (median=2, IQR=2) mRS score than LOW (median=1, IQR=1) and MED (median=1, IQR=1). The odds (OR) of good AIS outcome for LOW and MED were 1.8 (p=0.0001) and 1.6 (p=0.006) times higher than HIGH, respectively. Conclusion: Once accounted for clinical covariates, the excessive WMHv was associated with worse 3-month stroke outcomes. These data suggest that a life-time of injury to the white matter reflected in WMH is an important factor for stroke recovery and an indicator of the brain health.

Abstract 3681: Early Anticoagulation Is Not Associated With Hemorrhagic Transformation Of Ischemic Stroke In Patients With Atrial Fibrillation

Stroke ◽  
2012 ◽  
Vol 43 (suppl_1) ◽  
Author(s):  
H. B Brouwers ◽  
Svetlana Lorenzano ◽  
Lyndsey H Starks ◽  
David M Greer ◽  
Steven K Feske ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Clinical Data ◽  
Infarct Volume ◽  
Hemorrhagic Transformation ◽  
P Value ◽  
Long Term Outcome ◽  
Nihss Score

Purpose: Hemorrhagic transformation (HT) is a common and potentially devastating complication of ischemic stroke, however its prevalence, predictors, and outcome remain unclear. Early anticoagulation is thought to be a risk factor for HT which raises the clinical question when to (re)start anticoagulation in ischemic stroke patients who have a compelling indication, such as atrial fibrillation. We conducted a prospective cohort study to address this question and to identify association of hemorrhagic transformation with outcome measures in patients with atrial fibrillation in the setting of acute ischemic stroke. Materials and Methods: We performed a prospective study which enrolled consecutive patients admitted with acute ischemic stroke presenting to a single center over a three-year period. As part of the observational study, baseline clinical data and stroke characteristics as well as 3 month functional outcome were collected. For this sub-study, we restricted the analysis to subjects diagnosed with atrial fibrillation. CT and MRI scans were reviewed by experienced readers, blinded to clinical data, to assess for hemorrhagic transformation (using ECASS 2 criteria), microbleeds and infarct volumes in both admission and follow-up scans. Clinical and outcome data were analyzed for association with hemorrhagic transformation. Results: Of 94 patients, 63 had a history of atrial fibrillation (67.0%) and 31 had newly discovered atrial fibrillation (33.0%). We identified HT in 3 of 94 baseline scans (3.2%) and 22 of 48 follow-up scans (45.8%) obtained a median of 3 days post-stroke. In-hospital initiation of either anti-platelet (n = 36; OR 0.34 [95% CI 0.10-1.16], p-value = 0.09) or anticoagulation with unfractionated intravenous heparin or low molecular weight heparin (n = 72; OR 0.25 [95% CI 0.06-1.15], p-value = 0.08) was not associated with HT. Initial NIH Stroke Scale (NIHSS) score (median 13.0 [IQR 15.0] vs. 7.0 [IQR 10.0], p-value = 0.029) and baseline infarct volume (median 17 [IQR 42.03] vs. 5 [IQR 10.95], p-value = 0.011) were significantly higher in patients with HT compared to those without. Hemorrhagic transformation was associated with a significantly higher 48-hour median NIHSS score (20 [IQR 3.0] vs. 2 [IQR 3.25], p-value = 0.007) and larger final infarct volume (81.40 [IQR 82.75] vs. 9.95 [IQR 19.73], p-value < 0.001). Finally, we found a trend towards poorer 3-month modified Rankin Scale scores in subjects with HT (OR 11.25 [95% CI 0.97-130.22], p-value = 0.05). Conclusion: In patients with atrial fibrillation, initial NIHSS score and baseline infarct volume are associated with hemorrhagic transformation in acute ischemic stroke. Early initiation of antithrombotic therapy was not associated with hemorrhagic transformation. Patients with hemorrhagic transformation were found to have a poorer short and long term outcome and larger final infarct volumes.

scholarly journals Non-Coding RNA in Acute Ischemic Stroke: Mechanisms, Biomarkers and Therapeutic Targets

2018 ◽  
Vol 27 (12) ◽  
pp. 1763-1777 ◽  
Author(s):  
Sheng-Wen Wang ◽  
Zhong Liu ◽  
Zhong-Song Shi
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Neural Development ◽  
Therapeutic Targets ◽  
Circular Rnas ◽  
Non Coding Rna ◽  
Non Coding Rnas ◽  
Cerebral Ischemic ◽  
Functional Rnas ◽  
The Brain

Non-coding RNAs (ncRNAs) are a class of functional RNAs that regulate gene expression in a post-transcriptional manner. NcRNAs include microRNAs, long non-coding RNAs and circular RNAs. They are highly expressed in the brain and are involved in the regulation of physiological and pathophysiological processes, including cerebral ischemic injury, neurodegeneration, neural development, and plasticity. Stroke is one of the leading causes of death and physical disability worldwide. Acute ischemic stroke (AIS) occurs when brain blood flow stops, and that stoppage results in reduced oxygen and glucose supply to cells in the brain. In this article, we review the latest progress on ncRNAs in relation to their implications in AIS, as well as their potential as diagnostic and prognostic biomarkers. We also review ncRNAs acting as possible therapeutic targets in future precision medicine. Finally, we conclude with a brief discussion of current challenges and future directions for ncRNAs studies in AIS, which may facilitate the translation of ncRNAs research into clinical practice to improve clinical outcome of AIS.

scholarly journals KADAR FIBRIN MONOMER DAN UKURAN INFARK DI STROK ISKEMIK AKUT

2016 ◽  
Vol 20 (3) ◽  
pp. 171
Author(s):  
Ani Kartini ◽  
Mansyur Arif ◽  
Hardjoeno Hardjoeno
Keyword(s):  
Ischemic Stroke ◽  
Infarct Size ◽  
Acute Ischemic Stroke ◽  
Thrombus Formation ◽  
Infarct Volume ◽  
Cross Sectional Study ◽  
Cerebral Infarct ◽  
Cross Sectional ◽  
Fibrin Monomer ◽  
Significant Difference

Coagulation activation and thrombosis frequently exist in ischemic stroke, thrombus formation can be detected early by the presence of fibrin monomer. The purpose of this study was to know the correlation of fibrin monomer level with cerebral infarct size in acute ischemic stroke patients. This was a cross sectional study with a total of 39 samples. The fibrin monomer level was determined by immunoturbidimetry method using STA-Compact and the measurement of the infarct size was done by CT scan of the head using Broderick formula. The results of this study showed that the median level of fibrin monomer in acute ischemic stroke with nonlacunar infarct type and lacunar infarct type were 14.46 μg/mL and 4.29 μg/mL, respectively. Mann-Whitney test showed there was a significant difference of fibrin monomer levels between nonlacunar infarct type and the lacunar type, p=0.000. The cut-off point analysis result of the fibrin monomer level was 5.96 μg/mL with a sensitivity of 88.9% and specificity of 76.4%, respectively. Spearman correlation test showed that fibrin monomer level was positively correlated with cerebral infarct volume in acute ischemic stroke (r=0.56, p=0.000). Based on this study, it can be concluded that fibrin monomer level can be used as a marker to predict the type of cerebral infarct and volume of acute ischemic stroke as well.

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