scholarly journals Multimodal Optical Imaging to Investigate Spatiotemporal Changes in Cerebrovascular Function in AUDA Treatment of Acute Ischemic Stroke

2021 ◽  
Vol 15 ◽  
Author(s):  
Han-Lin Wang ◽  
Jia-Wei Chen ◽  
Shih-Hung Yang ◽  
Yu-Chun Lo ◽  
Han-Chi Pan ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Metabolic Rate ◽  
Acute Ischemic Stroke ◽  
Acute Phase ◽  
Laser Speckle ◽  
Control Group ◽  
Post Stroke ◽  
Optical Intrinsic Signal ◽  
Penumbra Region ◽  
Anti Inflammation

Administration of 12-(3-adamantan-1-yl-ureido)-dodecanoic acid (AUDA) has been demonstrated to alleviate infarction following ischemic stroke. Reportedly, the main effect of AUDA is exerting anti-inflammation and neovascularization via the inhibition of soluble epoxide hydrolase. However, the major contribution of this anti-inflammation and neovascularization effect in the acute phase of stroke is not completely elucidated. To investigate the neuroprotective effects of AUDA in acute ischemic stroke, we combined laser speckle contrast imaging and optical intrinsic signal imaging techniques with the implantation of a lab-designed cranial window. Forepaw stimulation was applied to assess the functional changes via measuring cerebral metabolic rate of oxygen (CMRO2) that accompany neural activity. The rats that received AUDA in the acute phase of photothrombotic ischemia stroke showed a 30.5 ± 8.1% reduction in the ischemic core, 42.3 ± 15.1% reduction in the ischemic penumbra (p < 0.05), and 42.1 ± 4.6% increase of CMRO2 in response to forepaw stimulation at post-stroke day 1 (p < 0.05) compared with the control group (N = 10 for each group). Moreover, at post-stroke day 3, increased functional vascular density was observed in AUDA-treated rats (35.9 ± 1.9% higher than that in the control group, p < 0.05). At post-stroke day 7, a 105.4% ± 16.4% increase of astrocytes (p < 0.01), 30.0 ± 10.9% increase of neurons (p < 0.01), and 65.5 ± 15.0% decrease of microglia (p < 0.01) were observed in the penumbra region in AUDA-treated rats (N = 5 for each group). These results suggested that AUDA affects the anti-inflammation at the beginning of ischemic injury and restores neuronal metabolic rate of O2 and tissue viability. The neovascularization triggered by AUDA restored CBF and may contribute to ischemic infarction reduction at post-stroke day 3. Moreover, for long-term neuroprotection, astrocytes in the penumbra region may play an important role in protecting neurons from apoptotic injury.

Abstract TP224: Interleukin-37 Level is Elevated in Acute Ischemic Stroke

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Saif Bushnaq ◽  
Atif Zafar ◽  
Kempuraj Duraisamy ◽  
Nudrat Tasneem ◽  
Mohammad M Khan ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Inflammatory Responses ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Delayed Presentation ◽  
Stroke Patients ◽  
Post Stroke ◽  
Urine And Serum ◽  
Serum And Urine

Background: Interleukin-37 (IL-37) is a new member of IL-1 cytokine family with a defined role as a negative feedback inhibitor of pro-inflammatory responses. IL-37 has yet to be evaluated in non-immune neurological diseases like ischemic or hemorrhagic stroke. This study aimed to measure the urine and serum IL-37 levels in patients with acute ischemic stroke. Method: Twelve patients consented for the study. Two sets of serum and urine samples were obtained and analyzed; one upon admission to the hospital, and the second the next morning after overnight fasting. The trends in serum level of IL-37 in 5 stroke patients, while trends in urine level of 6 patients were available, measured by real-time polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). Prior studies with healthy volunteers as control group have consistently showed IL-37 plasma level around or less than 65 pg/ml with maximum normal levels on ELISA approximated at 130 pg/ml. Results: IL-37 level in urine in stroke patients ranged from 297 - 4467. IL-37 levels were in the range of 300s to 1000s in patients with ischemic stroke compared with reported healthy controls in literature where the level was always less than 90. Three of these 10 patients presented within 3 hours of stroke onset with IL-37 serum levels being 2655 pg/ml, 3517 pg/ml and 5235 pg/ml. In all others, it ranged much less than that, with the trend of delayed presentation giving less IL-37 levels, both in urine and serum. There were no clear differences found in patients with or without tPA, diabetes, hyperlipidemia and high blood pressure in our small study. Conclusion: The study shows a rather stable elevation of IL-37 levels post-ischemic stroke, which if compared to available data from other studies, is 3-10 times elevated after acute ischemic stroke with an uptrend in the first few days. IL-37 plays some role in mediating post-stroke inflammation with significant rise in serum and urine IL-37 levels suggesting a key role of this novel cytokine in post-stroke pathology. This is the first ever reported study measuring and trending IL-37 levels in human plasma after an acute ischemic stroke.

scholarly journals New Candidates for Biomarkers and Drug Targets of Ischemic Stroke—A First Dynamic LC-MS Human Serum Proteomic Study

2022 ◽  
Vol 11 (2) ◽  
pp. 339
Author(s):  
Aleksandra Turek-Jakubowska ◽  
Janusz Dębski ◽  
Maciej Jakubowski ◽  
Ewa Szahidewicz-Krupska ◽  
Jakub Gawryś ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Heat Shock ◽  
Acute Ischemic Stroke ◽  
Human Serum ◽  
Acute Phase ◽  
Drug Targets ◽  
Control Group ◽  
Proteomic Study ◽  
Novel Drug ◽  
Novel Drug Targets

(1) Background: The aim of this dynamic-LC/MS-human-serum-proteomic-study was to identify potential proteins-candidates for biomarkers of acute ischemic stroke, their changes during acute phase of stroke and to define potential novel drug-targets. (2) Methods: A total of 32 patients (29–80 years) with acute ischemic stroke were enrolled to the study. The control group constituted 29 demographically-matched volunteers. Subjects with stroke presented clinical symptoms lasting no longer than 24 h, confirmed by neurological-examination and/or new cerebral ischemia visualized in the CT scans (computed tomography). The analysis of plasma proteome was performed using LC-MS (liquid chromatography–mass spectrometry). (3) Results: Ten proteins with significantly different serum concentrations between groups volunteers were: complement-factor-B, apolipoprotein-A-I, fibronectin, alpha-2-HS-glycoprotein, alpha-1B-glycoprotein, heat-shock-cognate-71kDa protein/heat-shock-related-70kDa-protein-2, thymidine phosphorylase-2, cytoplasmic-tryptophan-tRNA-ligase, ficolin-2, beta-Ala-His-dipeptidase. (4) Conclusions: This is the first dynamic LC-MS study performed on a clinical model which differentiates serum proteome of patients in acute phase of ischemic stroke in time series and compares to control group. Listed proteins should be considered as risk factors, markers of ischemic stroke or potential therapeutic targets. Further clinical validation might define their exact role in differential diagnostics, monitoring the course of the ischemic stroke or specifying them as novel drug targets.

scholarly journals INJECTED CITICOLINE IMPROVES IMPAIRMENT AND DISABILITY DURING ACUTE PHASE TREATMENT IN ISCHEMIC STROKE PATIENTS

2016 ◽  
Vol 51 (4) ◽  
pp. 245
Author(s):  
Rino Wahyudi ◽  
Didik Hasmono ◽  
Ruhaya Fitrina ◽  
Khairil Armal
Keyword(s):  
Ischemic Stroke ◽  
Treatment Group ◽  
Acute Ischemic Stroke ◽  
Acute Phase ◽  
Barthel Index ◽  
Recombinant Tissue Plasminogen Activator ◽  
Rank Test ◽  
Control Group ◽  
Before And After ◽  
Acute Phase Treatment

Treatment strategy of ischemic stroke is to reduce the extent of the damage and rescue neurons from death in the early days of ischemic events. Recombinant Tissue-Plasminogen Activator (r-TPA) is the only recommended therapy, but their use is very limited. Citicoline is a neuroprotectant with a therapeutic effect on several stages of the ischemic cascade. However, its use is still being debated. The purpose of this study was to analyze the use of supplementation citicoline injection in patients with acute ischemic stroke in relations to differences in changes in the level of interference (impairment), rate limitation (disability) and the level of obstruction (handicap) between the group receiving supplementation of citicoline injection 2x500 mg iv and the group without supplementation during acute phase treatment. This study was a prospective cohort study using experimental design in patients with acute ischemic stroke who met the inclusion and exclusion criteria with or without supplementation citicoline between January - April 2015 in the National Stroke Hospital, Bukittinggi. Rate of interference was assessed with NIHSS, level of limitations with Barthel Index, and level of obstruction with modified Rankin Scale. Assessment was done 2 times, before and after the treatment. Statistical methods used in this study were Wilcoxon signed rank test, paired T-test and Mann-Whitney test. This study was conducted on 50 subjects divided into 2 groups, a control group without supplementation and group treated with injected citicoline of 2x500 mg iv. Demographic and baseline characteristics did not differ between groups. There were differences in level of interference changes. Mean decrease in control group was 0.96 ± 1.74 NIHSS, while that in treatment group was 2.84 ± 1.46 NIHSS (p <0.05). There were differences in changes in the level of limitations. Mean increase of Barthel Index in control group 9.60 ± 11.17 and in treatment group 20.40 ± 13.99 (p <0.05). However, changes in the level obstacle showed no difference. In conclusion, citicoline injection supplementation in patients with ischemic stroke during acute phase treatment showed improvement differences in changes in the level of distraction (impairment) and the rate limitations (disability), but showed no difference in changes in the level of obstruction (handycaps).

scholarly journals Characterization of the soluble fibrin monomer complexes in patients with acute and one year post acute ischemic stroke

2017 ◽  
Vol 22 (1) ◽  
pp. 58-61
Author(s):  
T. Katrii ◽  
N. Shabanova ◽  
S. Ostapchuk ◽  
O. Savchuk
Keyword(s):  
Ischemic Stroke ◽  
Blood Plasma ◽  
Acute Ischemic Stroke ◽  
Acute Phase ◽  
Soluble Fibrin ◽  
Post Stroke ◽  
Fibrin Monomer ◽  
Healthy Donors ◽  
One Year

It was shown that atherothrombotic and cardioembolic subtypes of ischemic stroke in acute phase of the disease accompanied with the appearance of the high concentrated soluble fibrin monomer complexes in blood plasma. But the concentration returned to the norm one year post ischemic stroke attack. Instead the concentration, the qualitative content of the year post stroke SFMC fraction was characterized by the higher diversity in comparison with acute fraction both subtypes of ischemic stroke as well as the healthy donors. The different qualitative content of the SFMC fraction was observed for the both tested subtypes of ischemic stroke. The higher diversity of SFMC fractions was showed for the cardioembolic subtypes of ischemic stroke.

scholarly journals Selective intra-carotid blood cooling in acute ischemic stroke: A safety and feasibility study in an ovine stroke model

2021 ◽  
pp. 0271678X2110249
Author(s):  
Giorgio FM Cattaneo ◽  
Andrea M Herrmann ◽  
Sebastian A Eiden ◽  
Manuela Wieser ◽  
Elias Kellner ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Carotid Artery ◽  
Acute Ischemic Stroke ◽  
Neurological Outcome ◽  
Artery Occlusion ◽  
Control Group ◽  
Stroke Model ◽  
Primary Endpoints ◽  
Neuroprotective Strategy ◽  
Vessel Patency

Selective therapeutic hypothermia (TH) showed promising preclinical results as a neuroprotective strategy in acute ischemic stroke. We aimed to assess safety and feasibility of an intracarotid cooling catheter conceived for fast and selective brain cooling during endovascular thrombectomy in an ovine stroke model. Transient middle cerebral artery occlusion (MCAO, 3 h) was performed in 20 sheep. In the hypothermia group (n = 10), selective TH was initiated 20 minutes before recanalization, and was maintained for another 3 h. In the normothermia control group (n = 10), a standard 8 French catheter was used instead. Primary endpoints were intranasal cooling performance (feasibility) plus vessel patency assessed by digital subtraction angiography and carotid artery wall integrity (histopathology, both safety). Secondary endpoints were neurological outcome and infarct volumes. Computed tomography perfusion demonstrated MCA territory hypoperfusion during MCAO in both groups. Intranasal temperature decreased by 1.1 °C/3.1 °C after 10/60 minutes in the TH group and 0.3 °C/0.4 °C in the normothermia group (p < 0.001). Carotid artery and branching vessel patency as well as carotid wall integrity was indifferent between groups. Infarct volumes (p = 0.74) and neurological outcome (p = 0.82) were similar in both groups. Selective TH was feasible and safe. However, a larger number of subjects might be required to demonstrate efficacy.

scholarly journals Actigraphic Measurement of the Upper Limbs for the Prediction of Ischemic Stroke Prognosis: An Observational Study

Sensors ◽  
2021 ◽  
Vol 21 (7) ◽  
pp. 2479
Author(s):  
Giuseppe Reale ◽  
Silvia Giovannini ◽  
Chiara Iacovelli ◽  
Stefano Filippo Castiglia ◽  
Pietro Picerno ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Observational Study ◽  
Acute Ischemic Stroke ◽  
Acute Phase ◽  
Stroke Unit ◽  
Prognostic Model ◽  
Recovery Process ◽  
Motor Deficits ◽  
Stroke Patients ◽  
Movement Asymmetry

Background: It is often challenging to formulate a reliable prognosis for patients with acute ischemic stroke. The most accepted prognostic factors may not be sufficient to predict the recovery process. In this view, describing the evolution of motor deficits over time via sensors might be useful for strengthening the prognostic model. Our aim was to assess whether an actigraphic-based parameter (Asymmetry Rate Index for the 24 h period (AR2_24 h)) obtained in the acute stroke phase could be a predictor of a 90 d prognosis. Methods: In this observational study, we recorded and analyzed the 24 h upper limb movement asymmetry of 20 consecutive patients with acute ischemic stroke during their stay in a stroke unit. We recorded the motor activity of both arms using two programmable actigraphic systems positioned on patients’ wrists. We clinically evaluated the stroke patients by NIHSS in the acute phase and then assessed them across 90 days using the modified Rankin Scale (mRS). Results: We found that the AR2_24 h parameter positively correlates with the 90 d mRS (r = 0.69, p < 0.001). Moreover, we found that an AR2_24 h > 32% predicts a poorer outcome (90 d mRS > 2), with sensitivity = 100% and specificity = 89%. Conclusions: Sensor-based parameters might provide useful information for predicting ischemic stroke prognosis in the acute phase.

Abstract WP7: Leukoaraiosis And Outcomes After Intra-arterial Therapy In Acute Ischemic Stroke

Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
Dan-Victor V Giurgiutiu ◽  
Albert J Yoo ◽  
Kaitlin Fitzpatrick ◽  
Zeshan Chaudhry ◽  
Lee H Schwamm ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Functional Outcome ◽  
Univariate Analysis ◽  
Multivariable Analysis ◽  
Artery Occlusion ◽  
Post Stroke ◽  
Good Functional Outcome ◽  
Grade 3 ◽  
Risk Of Hemorrhage

Background: Selecting patients most likely to benefit (MLTB) from intra-arterial therapy (IAT) is essential to assure favorable outcomes after intervention for acute ischemic stroke (AIS). Leukoaraiosis (LA) has been linked to infarct growth, risk of hemorrhage after IV rt-PA, and poor post-stroke outcomes. We investigated whether LA severity is associated with AIS outcomes after IAT. Methods: We analyzed consecutive AIS subjects from our institutional GWTG-Stroke database enrolled between 01/01/2007-06/30/2009, who met our pre-specified criteria for MLTB: CTA and MRI within 6 hours from last known well, NIHSS score ≥8, baseline DWI volume (DWIv) ≤ 100 cc, and proximal artery occlusion and were treated with IAT. LA volume (LAv) was assessed on FLAIR using validated, semi-automated protocols. We analyzed CTA to assess collateral grade; post-IAT angiogram for recanalization status (TICI score ≥2B); and the 24-hour CT for symptomatic ICH (sICH). Logistic regression was used to determine independent predictors of good functional outcome (mRS≤ 2) and mortality at 90 days post-stroke. Results: There were 48 AIS subjects in this analysis (mean age 69.2, SD±13.8; 55% male; median LAv 4cc, IQR 2.2-8.8cc; median NIHSS 15, IQR 13-19; median DWIv 15.4cc, IQR 9.2-20.3cc). Of these, 34 (72%) received IV rt-PA; 3 (6%) had sICH; 21 (44.7%) recanalized; and 23 (50%) had collateral grade ≥3. At 90 days, 15/48 (36.6%) were deceased and 15/48 had mRS≤ 2. In univariate analysis, recanalization (OR 6.2, 95%CI 1.5-25.5), NIHSS (OR 0.8 per point, 95%CI 0.64-0.95), age (OR 0.95 per yr, 95%CI 0.89-0.99) were associated with good outcome, whereas age (OR 1.1, 95%CI 1.01-1.14) and HTN (OR 5.6, 95%CI 1.04-29.8) were associated with mortality. In multivariable analysis including age, NIHSS, recanalization, collateral grade, and LAv, only recanalization independently predicted good functional outcome (OR 21.3, 95%CI 2.3-199.9) and reduced mortality (OR 0.15, 95%CI 0.02-1.12) after IAT. Conclusions: LA severity is not associated with poor outcome in patients selected MLTB for IAT. Among AIS patients considered likely to benefit from IAT, only recanalization independently predicted good functional outcome and decreased mortality.

scholarly journals Efficacy and safety of cinepazide maleate injection in patients with acute ischemic stroke: A multicenter, randomized, double-blind, placebo-controlled trial

2020 ◽  
Author(s):  
Jun Ni ◽  
Huisheng Chen ◽  
Guofang Chen ◽  
Yong Ji ◽  
Fei Yi ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Thrombolytic Therapy ◽  
Acute Ischemic Stroke ◽  
Barthel Index ◽  
Controlled Trial ◽  
Survival Rates ◽  
Control Group ◽  
Efficacy And Safety ◽  
Clinical Trial Registry ◽  
Double Blind

Abstract Background: Ischemic stroke is a leading cause of morbidity and mortality. Thrombolytic therapy improves disability and survival rates; however, to be effective, it must be given within 4.5 hours of onset. Moreover, thrombolytic therapy is frequently contraindicated. Therefore, alternative therapeutic options are required. In China, cinepazide maleate injection has been shown to improve the cerebral collateral circulation and further reduce disability in stroke patients; however, very few studies investigating this therapy have been conducted to date. Therefore, this study aimed to further confirm the efficacy and safety of cinepazide maleate injection in patients with acute ischemic stroke.Methods: Patients with acute ischemic stroke were administered an intravenous infusion of 320 mg cinepazide maleate or placebo once daily for 14 days. All patients were also administered basic therapy (citicoline sodium). The primary efficacy endpoint was the proportion of patients with a modified Rankin scale (mRS) ≤2 on day 90. Secondary efficacy endpoints included Barthel Index ≥95. Safety was evaluated by recording all adverse events (AEs), monitoring laboratory parameters and vital signs, and electrocardiogram.Results: In total, 937 patients with an acute ischemic stroke were included, with a mean (standard deviation, SD) National Institutes of Health Stroke Scale score of 8.8 (2.4) and a mean (SD) stroke onset of 30.9 (11.4) hours prior. Following treatment for 90 days, the proportion of patients with an mRS score ≤2 was significantly higher in the cinepazide maleate group than in the control group (60.9% vs. 50.1%; p=0.0004). Moreover, the proportion of patients with a Barthel Index of ≥95 on day 90 was also significantly higher in the cinepazide maleate group than in the control group (53.4% vs. 46.7%; p=0.0230). There were no statistically significant differences in safety parameters between the cinepazide maleate and control groups.Conclusions: The results of this study show that cinepazide maleate injection is superior to placebo in improving neurological function and activities of daily living, reducing disability, and promoting functional recovery in patients with acute ischemic stroke. Cinepazide maleate injection was safe and well tolerated with no unexpected AEs reported.Trial registration: Chinese Clinical Trial Registry CTR20160292 and ChiCTR1900023827. Retrospectively registered June 13, 2019.

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