Abstract P777: Statistical Modeling of Proteomic Signaling During Stroke in Patients Undergoing Thrombectomy

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Sydney Claypoole ◽  
Jacqueline Frank ◽  
Madison Sands ◽  
Christopher J McLouth ◽  
Jill Roberts ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Statistical Modeling ◽  
Internal Control ◽  
Stepwise Regression ◽  
Infarct Volume ◽  
Tissue Samples ◽  
Bivariate Regression ◽  
Inflammatory Proteins ◽  
The Relationship ◽  
Proximity Extension Assay

Introduction: The previously published Blood and Clot Thrombectomy Registry and Collaboration (BACTRAC) protocol (clinicaltrials.gov NCT03153683) utilizes mechanical thrombectomy to obtain tissue samples for banking. Peripheral blood proximal to the clot and intracranial blood distal from the clot were isolated. Proteomic and statistical analyses revealed normalized (intracranial-systemic) CCL19 expression was a predictor of infarct volume. Statistical modeling analyses were used determine the CCL19-associated proteomic signaling network occurring during ischemic stroke relating to infarct volume. Methods: Arterial intracranial and systemic blood samples underwent analysis for inflammatory proteins using Proximity Extension Assay (PEA) via Olink (Olink Proteomics, Boston, MA). Systemic expression was used as an internal control to normalize expression in the intracranial blood. Bivariate regression was used to examine the relationship between the intracranial normalized CCL19 expression and infarct volume. A backwards stepwise regression was then used to determine a model of predictability of infarct volume by CCL19 and associated inflammatory proteins. Results: 25 subjects (>18 yrs) with a mean infarct volume of 8,172 ± 82,284 mm 3 and mean infarct time of 513 ± 246 minutes were included in this study. Their median age was 64 (24-91) and 10 (40%) were male. 16 subjects (64%) had hypertension, 15 (60%) had BMI > 25, and 6 (24%) had a previous stroke. The stepwise regression model shows normalized expression of 16 proteins correlated with an increase in infarct volume (p<0.005): CCL20, CXCL1, OSM, CD6, OSMR, TGF-alpha, TRANCE, CXCL10, LIF-R, CCL19, CDCP1, Flt3L, CCL23, CD244, TRAIL, NOTCH1. Conclusions: In our model, the expression of these proteins were consistently changed, though the directionality differed. LIF-R, NOTCH1, TRAIL, CD6, CCL23, TGF-alpha, and CCL20 were positively correlated, while the expressions of Flt3L, OSM, OSMR, TRANCE, CD244, CDCP1, CXCL1, CXCL10, and CCL19 were negatively correlated with infarct volume. This model depicts the proteomic signaling occurring during stroke in relationship to infarct volume, which reveals potential biomarkers and therapeutic targets for the early phase of ischemic stroke.

Abstract P798: Antimicrobial Protein Reg3a and Network Inflammatory Proteins Are Predictive of Infarct Volume and Functional Impairment in Ischemic Stroke

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Madison Sands ◽  
Jacqueline Frank ◽  
Chris McLouth ◽  
Benton Maglinger ◽  
Jill Roberts ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Ischemic Stroke ◽  
Stepwise Regression ◽  
Inflammatory Responses ◽  
Therapeutic Potential ◽  
Infarct Volume ◽  
Antimicrobial Protein ◽  
Immune Mediated ◽  
Inflammatory Processes ◽  
Inflammatory Proteins

Introduction: Regenerating Family Member 3 Alpha (REG3A) is an antimicrobial protein secreted by the intestine and pancreas. REG3A is involved in immune-mediated inflammatory responses and helps maintain homeostasis of the gut microbiome. REG3A is elevated in patients with ischemic stroke, but its role within the gut-brain axis during stroke remains unclear. Our aim was to examine the association of plasma REG3A levels with other signaling proteins in systemic plasma during stroke, and its correlation with clinical outcomes of ischemic stroke. Methods: Intracranial and systemic plasma samples from n=25 thrombectomy subjects underwent Proximity Extension Assay via Olink Proteomics. REG3A levels and inflammatory markers were examined using bivariate regressions. Stepwise regression determined the predictability of infarct volume by REG3A. Two-tailed t-tests were used to examine the relationship between the National Institutes of Health Stroke Scale (NIHSS) and levels of REG3A. Results: Increased expression of systemic REG3A correlated with increases in infarct volume (p=.009, R=.514). Stepwise regression predicting infarct volume yielded a model including REG3A and systemic proteins such as CCL19, IL15, and IL1α (P<.001, R=.980). NIHSS scores corresponding to moderate-severe/severe strokes had increased intracranial REG3A (p<.05) and increased ratios of intracranial:systemic REG3A expression (p=.05). Conclusions: Within a network of proteins, REG3A is predictive of increased infarct volume and decreased function. Studies suggest that IL17 and IL6 induce REG3A expression. Subsequent REG3A can interact with NFkB, which transcriptionally regulates CCL19, IL1α, and IL15. In the intestine, REG3A regulates microbial synthesis of fatty acids and inflammatory processes. Fatty acids suppress cytokines such as IL6 and IL1α and are reportedly neuroprotective in stroke. Increase of systemic REG3A may reflect cellular responses to gut dysbiosis and inflammation triggered from ischemic stroke. Future studies will examine prognostic and therapeutic potential of the REG3A pathway in large vessel occlusive stroke.

scholarly journals Role of regulatory T-cells on ischemic stroke outcome: new clinical evidences

2019 ◽  
Author(s):  
María Santamaría-Cadavid ◽  
Emilio Rodríguez-Castro ◽  
Manuel Rodríguez-Yáñez ◽  
Susana Arias-Rivas ◽  
Iria López-Dequidt ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Functional Outcome ◽  
Infarct Volume ◽  
Treg Cells ◽  
Potential Therapeutic Target ◽  
Control Subjects ◽  
Good Functional Outcome ◽  
Early Neurological Deterioration ◽  
The Relationship

Abstract Background: Recent preclinical studies have shown that regulatory T (Treg) cells play a key role in the immune response after ischemic stroke (IS). However, the role of Treg-cells in human acute IS has been poorly investigated. Our aim was to study the relationship between circulating Treg-cells and outcome in human IS patients.Methods Methods: A total of 204 IS patients and 22 control subjects were recruited. The main study variable was good functional outcome at 3 months (modified Rankin scale ≤2) considering infarct volume, Early Neurological Deterioration (END) and risk of infections as secondary variables. The percentage of circulating Treg-cells was measured at admission, 48, 72h and at day 7 after stroke onset.Results Results: Circulating Treg-cell levels were higher in IS patients compared to control subjects. Treg-cells at 48h were independently associated with good functional outcome (OR, 3.5; CI: 1.9-7.8) after adjusting by confounding factors. Patients with lower Treg-cells at 48h showed higher frequency of END and risk of infections. In addition, a negative correlation was found between circulating Treg-cells at 48h (r=-0.414) and 72h (r=-0.418) and infarct volume. Conclusions: These findings suggest that Treg-cells may participate in the recovery of IS patients. Therefore, Treg-cells may be considered a potential therapeutic target in acute ischemic stroke.

scholarly journals Regulatory T cells participate in the recovery of ischemic stroke patients

2020 ◽  
Author(s):  
María Santamaría-Cadavid ◽  
Emilio Rodríguez-Castro ◽  
Manuel Rodríguez-Yáñez ◽  
Susana Arias-Rivas ◽  
Iria López-Dequidt ◽  
...  
Keyword(s):  
T Cells ◽  
Ischemic Stroke ◽  
Regulatory T Cells ◽  
Functional Outcome ◽  
Infarct Volume ◽  
Control Subjects ◽  
Good Functional Outcome ◽  
Early Neurological Deterioration ◽  
The Relationship

Abstract Background: Recent preclinical studies have shown that regulatory T cells (Treg) play a key role in the immune response after ischemic stroke (IS). However, the role of Treg in human acute IS has been poorly investigated. Our aim was to study the relationship between circulating Treg and outcome in human IS patients. Methods: A total of 204 IS patients and 22 control subjects were recruited. The main study variable was good functional outcome at 3 months (modified Rankin scale ≤2) considering infarct volume, Early Neurological Deterioration (END) and risk of infections as secondary variables. The percentage of circulating Treg was measured at admission, 48, 72h and at day 7 after stroke onset. Results: Circulating Treg levels were higher in IS patients compared to control subjects. Treg at 48h were independently associated with good functional outcome (OR, 3.5; CI: 1.9-7.8) after adjusting by confounding factors. Patients with lower Treg at 48h showed higher frequency of END and risk of infections. In addition, a negative correlation was found between circulating Treg at 48h (r=-0.414) and 72h (r=-0.418) and infarct volume. Conclusions: These findings suggest that Treg may participate in the recovery of IS patients. Therefore, Treg may be considered a potential therapeutic target in acute ischemic stroke.

scholarly journals Mediation of the Relationship Between Endovascular Therapy and Functional Outcome by Follow-up Infarct Volume in Patients With Acute Ischemic Stroke

2019 ◽  
Vol 76 (2) ◽  
pp. 194 ◽  
Author(s):  
Anna M. M. Boers ◽  
Ivo G. H. Jansen ◽  
Scott Brown ◽  
Hester F. Lingsma ◽  
Ludo F. M. Beenen ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Functional Outcome ◽  
Endovascular Therapy ◽  
Infarct Volume ◽  
The Relationship

The relationship of oxidative stress parameters with infarct volume and National Institutes of Health Stroke Scale in ischemic stroke / İskemik inmede oksidatif stres parametrelerinin infarkt volümü ve National Institutes of Health Stroke Scale ile ilişkisi

2015 ◽  
Vol 40 (4) ◽  
Author(s):  
Ferhat İçme ◽  
Özcan Erel ◽  
Zeynep Saral Öztürk ◽  
Tolga Öz ◽  
Akkan Avci ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Ischemic Stroke ◽  
Infarct Volume ◽  
National Institutes Of Health ◽  
Control Group ◽  
Case Group ◽  
Ischemic Lesion ◽  
Oxidative Stress Parameters ◽  
The Relationship ◽  
Stress Parameters

AbstractObjective: What we know about the relationship between oxidative stress parameters and ischemic stroke is still limited and controversial. Our study aimed to investigate the relationships among ischemic lesion volume, National Institutes of Health Stroke Scale (NIHSS) values, and oxidant and antioxidant levels to determine whether oxidative stress paramaters is effective on stroke severity in ischemic stroke patients.Methods: The study included 34 patients with ischemic stroke and 34 volunteers with no active diseases. Total Oxidant Status (TOS), Total Antioxidant Status (TAS), thiol, paraoxonase, stimulated paraoxonase (stparaoxonase) and arylesterase were measured in blood samples collected on admission from patients diagnosed with ischemic stroke. The Oxidative Stress Index (OSI) was calculated. The same oxidative stress parameters were measured in the control group and compared with the patient group. Correlation between the oxidative stress parameters, the infarct volume and the NIHSS was studied. NIHSS was calculated when patients were admitted to the emergency department. The infarct volume was calculated using diffusion-weighted magnetic resonance imaging performed in the first 72-96 hours.Results: TOS and OSI values were significantly higher in the case group than the control group. Paraoxonase, arylesterase, and thiol values were significantly lower in the case group than the control group. TAS and stparaoxonase values weren’t differed significantly between the case and control groups. There were significant negative correlations between the NIHSS value and both the paraoxonase value and stparaoxonase value. There were no significant correlations between the NIHSS value and the infarct volume and the TAS, TOS, OSI, arylesterase, and thiol values.Conclusion: We concluded that change in oxidative stress balance in favor of oxidants could be a cause in the pathogenesis of ischemic stroke but oxidative stress alone can’t be sufficient in predicting the severity of stroke.

scholarly journals Regulatory T cells participate in the recovery of ischemic stroke patients

2019 ◽  
Author(s):  
María Santamaría-Cadavid ◽  
Emilio Rodríguez-Castro ◽  
Manuel Rodríguez-Yáñez ◽  
Susana Arias-Rivas ◽  
Iria López-Dequidt ◽  
...  
Keyword(s):  
T Cells ◽  
Ischemic Stroke ◽  
Regulatory T Cells ◽  
Functional Outcome ◽  
Infarct Volume ◽  
Control Subjects ◽  
Good Functional Outcome ◽  
Early Neurological Deterioration ◽  
The Relationship

Abstract Background: Recent preclinical studies have shown that regulatory T cells (Treg) play a key role in the immune response after ischemic stroke (IS). However, the role of Treg in human acute IS has been poorly investigated. Our aim was to study the relationship between circulating Treg and outcome in human IS patients. Methods: A total of 204 IS patients and 22 control subjects were recruited. The main study variable was good functional outcome at 3 months (modified Rankin scale ≤2) considering infarct volume, Early Neurological Deterioration (END) and risk of infections as secondary variables. The percentage of circulating Treg was measured at admission, 48, 72h and at day 7 after stroke onset. Results: Circulating Treg levels were higher in IS patients compared to control subjects. Treg at 48h were independently associated with good functional outcome (OR, 3.5; CI: 1.9-7.8) after adjusting by confounding factors. Patients with lower Treg at 48h showed higher frequency of END and risk of infections. In addition, a negative correlation was found between circulating Treg at 48h (r=-0.414) and 72h (r=-0.418) and infarct volume. Conclusions: These findings suggest that Treg may participate in the recovery of IS patients. Therefore, Treg may be considered a potential therapeutic target in acute ischemic stroke.

scholarly journals MicroRNA-29b is a Therapeutic Target in Cerebral Ischemia Associated with Aquaporin 4

2015 ◽  
Vol 35 (12) ◽  
pp. 1977-1984 ◽  
Author(s):  
Yang Wang ◽  
Jun Huang ◽  
Yuanyuan Ma ◽  
Guanghui Tang ◽  
Yanqun Liu ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Cerebral Ischemia ◽  
Infarct Volume ◽  
White Blood Cells ◽  
Aquaporin 4 ◽  
Luciferase Reporter ◽  
Reporter System ◽  
Brain Infarct ◽  
Relationship Of ◽  
The Relationship

MicroRNA-29b (miR-29b) is involved in regulating ischemia process, but the molecular mechanism is unclear. In this work, we explored the function of miR-29b in cerebral ischemia. The level of miR-29b in white blood cells was evaluated in patients and mice after ischemic stroke. Brain infarct volume and National Institute of Health stroke scale (NIHSS) scores were analyzed to determine the relationship between miR-29b expression and the severity of stroke. The relationship of miR-29b and aquaporin-4 (AQP4) was further studied in mice. We found that miR-29b was significantly downregulated in stroke patients ( P < 0.05). MiR-29b level negatively associated with NIHSS scores ( r = −0.349, P < 0.01) and brain infarct volume ( r = −0.321, P < 0.05). In ischemic mice, miR-29b in the brain and blood were both downregulated ( r =0.723, P < 0.05). MiR-29b overexpression reduced infarct volume (49.50 ±6.55 versus 35.48 ±2.28 mm3, P < 0.05), edema (164±4% versus 108±4%, P < 0.05), and blood-brain barrier (BBB) disruption compared with controls (15 ±9% versus 7 ±3%, P < 0.05). Aquaporin-4 expression greatly decreased after miR-29b overexpression (28±7% versus 11 ±3%, P < 0.05). Dual-luciferase reporter system showed that AQP-4 was the direct target of miR-29b ( P < 0.05). We concluded that miR-29b could potentially predict stroke outcomes as a novel circulating biomarker, and miR-29b overexpression reduced BBB disruption after ischemic stroke via downregulating AQP-4.

The Relationship between Acute Stress Hyperglycemia and Infarct Volume in Ischemic Stroke (P07.032)

Neurology ◽  
2012 ◽  
Vol 78 (Meeting Abstracts 1) ◽  
pp. P07.032-P07.032
Author(s):  
J. Helenius ◽  
R. Avery ◽  
B. Polnar ◽  
J. A. Caceres ◽  
M. Siket ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Stress ◽  
Infarct Volume ◽  
Stress Hyperglycemia ◽  
The Relationship

scholarly journals Regulatory T cells participate in the recovery of ischemic stroke patients

2019 ◽  
Author(s):  
María Santamaría-Cadavid ◽  
Emilio Rodríguez-Castro ◽  
Manuel Rodríguez-Yáñez ◽  
Susana Arias-Rivas ◽  
Iria López-Dequidt ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Functional Outcome ◽  
Infarct Volume ◽  
Treg Cells ◽  
Potential Therapeutic Target ◽  
Control Subjects ◽  
Good Functional Outcome ◽  
Early Neurological Deterioration ◽  
The Relationship

Abstract Background: Recent preclinical studies have shown that regulatory T (Treg) cells play a key role in the immune response after ischemic stroke (IS). However, the role of Treg-cells in human acute IS has been poorly investigated. Our aim was to study the relationship between circulating Treg-cells and outcome in human IS patients.Methods Methods: A total of 204 IS patients and 22 control subjects were recruited. The main study variable was good functional outcome at 3 months (modified Rankin scale ≤2) considering infarct volume, Early Neurological Deterioration (END) and risk of infections as secondary variables. The percentage of circulating Treg-cells was measured at admission, 48, 72h and at day 7 after stroke onset.Results Results: Circulating Treg-cell levels were higher in IS patients compared to control subjects. Treg-cells at 48h were independently associated with good functional outcome (OR, 3.5; CI: 1.9-7.8) after adjusting by confounding factors. Patients with lower Treg-cells at 48h showed higher frequency of END and risk of infections. In addition, a negative correlation was found between circulating Treg-cells at 48h (r=-0.414) and 72h (r=-0.418) and infarct volume.Conclusions Conclusions: These findings suggest that Treg-cells may participate in the recovery of IS patients. Therefore, Treg-cells may be considered a potential therapeutic target in acute ischemic stroke.

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