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 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 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

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.

Abstract WMP15: Automated Volumetric Assessment of Infarct Core in Non-Contrast Computed Tomography in Patients With Acute Ischemic Stroke Secondary to Large Vessel Occlusion

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Alvaro Garcia-Tornel ◽  
Matias Deck ◽  
Marc Ribo ◽  
David Rodriguez-Luna ◽  
Jorge Pagola ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Functional Outcome ◽  
Infarct Volume ◽  
Large Vessel Occlusion ◽  
Infarct Core ◽  
Vessel Occlusion ◽  
Good Functional Outcome ◽  
Volumetric Assessment

Introduction: Perfusion imaging has emerged as an imaging tool to select patients with acute ischemic stroke (AIS) secondary to large vessel occlusion (LVO) for endovascular treatment (EVT). We aim to compare an automated method to assess the infarct ischemic core (IC) in Non-Contrast Computed Tomography (NCCT) with Computed Tomography Perfusion (CTP) imaging and its ability to predict functional outcome and final infarct volume (FIV). Methods: 494 patients with anterior circulation stroke treated with EVT were included. Volumetric assessment of IC in NCCT (eA-IC) was calculated using eASPECTS™ (Brainomix, Oxford). CTP was processed using availaible software considering CTP-IC as volume of Cerebral Blood Flow (CBF) <30% comparing with the contralateral hemisphere. FIV was calculated in patients with complete recanalization using a semiautomated method with a NCCT performed 48-72 hours after EVT. Complete recanalization was considered as modified Thrombolysis In Cerebral Ischemia (mTICI) ≥2B after EVT. Good functional outcome was defined as modified Rankin score (mRs) ≤2 at 90 days. Statistical analysis was performed to assess the correlation between EA-IC and CTP-IC and its ability to predict prognosis and FIV. Results: Median eA-IC and CTP-IC were 16 (IQR 7-31) and 8 (IQR 0-28), respectively. 419 patients (85%) achieved complete recanalization, and their median FIV was 17.5cc (IQR 5-52). Good functional outcome was achieved in 230 patients (47%). EA-IC and CTP-IC had moderate correlation between them (r=0.52, p<0.01) and similar correlation with FIV (r=0.52 and 0.51, respectively, p<0.01). Using ROC curves, both methods had similar performance in its ability to predict good functional outcome (EA-IC AUC 0.68 p<0.01, CTP-IC AUC 0.66 p<0.01). Multivariate analysis adjusted by confounding factors showed that eA-IC and CTP-IC predicted good functional outcome (for every 10cc and >40cc, OR 1.5, IC1.3-1.8, p<0.01 and OR 1.3, IC1.1-1.5, p<0.01, respectively). Conclusion: Automated volumetric assessment of infarct core in NCCT has similar performance predicting prognosis and final infarct volume than CTP. Prospective studies should evaluate a NCCT-core / vessel occlusion penumbra missmatch as an alternative method to select patients for EVT.

Abstract WMP17: Computerized Tomography Perfusion to Characterize Lack of Clinical Improvement After Recanalization in Acute Ischemic Stroke

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Alvaro Garcia-Tornel ◽  
Marta Olive-Gadea ◽  
Marc Ribo ◽  
David Rodriguez-Luna ◽  
Jorge Pagola ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Functional Outcome ◽  
Infarct Volume ◽  
Significant Proportion ◽  
Hemorrhagic Transformation ◽  
Vessel Occlusion ◽  
Clinical Recovery ◽  
Good Functional Outcome ◽  
Significant Difference

A significant proportion of patients with acute ischemic stroke (AIS) treated with endovascular thrombectomy (EVT) present poor functional outcome despite recanalization. We aim to investigate computed tomography perfusion (CTP) patterns after EVT and their association with outcome Methods: Prospective study of anterior large vessel occlusion AIS patients who achieved complete recanalization (defined as modified Thrombolysis in Cerebral Ischemia (TICI) 2b - 3) after EVT. CTP was performed within 30 minutes post-EVT recanalization (POST-CTP): hypoperfusion was defined as volume of time to maximal arrival of contrast (Tmax) delay ≥6 seconds in the affected territory. Hyperperfusion was defined as visual increase in cerebral blood flow (CBF) and volume (CBV) with advanced Tmax compared with the unaffected hemisphere. Dramatic clinical recovery (DCR) was defined as a decrease of ≥8 points in NIHSS score at 24h or NIHSS≤2 and good functional outcome by mRS ≤2 at 3 months. Results: One-hundred and forty-one patients were included. 49 (34.7%) patients did not have any perfusion abnormality on POST-CTP, 60 (42.5%) showed hypoperfusion (median volume Tmax≥6s 17.5cc, IQR 6-45cc) and 32 (22.8%) hyperperfusion. DCR appeared in 56% of patients and good functional outcome in 55.3%. Post-EVT hypoperfusion was related with worse final TICI, and associated worse early clinical evolution, larger final infarct volume (p<0.01 for all) and was an independent predictor of functional outcome (OR 0.98, CI 0.97-0.99, p=0.01). Furthermore, POST-CTP identified patients with delayed improvement: in patients without DCR (n=62, 44%), there was a significant difference in post-EVT hypoperfusion volume according to functional outcome (hypoperfusion volume of 2cc in good outcome vs 11cc in poor outcome, OR 0.97 CI 0.93-0.99, p=0.04), adjusted by confounding factors. Hyperperfusion was not associated with worse outcome (p=0.45) nor symptomatic hemorrhagic transformation (p=0.55). Conclusion: Hypoperfusion volume after EVT is an accurate predictor of functional outcome. In patients without dramatic clinical recovery, hypoperfusion predicts good functional outcome and defines a “stunned-brain” pattern. POST-CTP may help to select EVT patients for additional therapies.

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

scholarly journals CD28 Superagonist-Mediated Boost of Regulatory T Cells Increases Thrombo-Inflammation and Ischemic Neurodegeneration during the Acute Phase of Experimental Stroke

2014 ◽  
Vol 35 (1) ◽  
pp. 6-10 ◽  
Author(s):  
Michael K Schuhmann ◽  
Peter Kraft ◽  
Guido Stoll ◽  
Kristina Lorenz ◽  
Sven G Meuth ◽  
...  
Keyword(s):  
T Cells ◽  
Ischemic Stroke ◽  
Regulatory T Cells ◽  
Thrombus Formation ◽  
Inflammatory Lesion ◽  
Artery Occlusion ◽  
Acute Stage ◽  
Experimental Stroke ◽  
Cerebral Artery Occlusion

While the detrimental role of non-regulatory T cells in ischemic stroke is meanwhile unequivocally recognized, there are controversies about the properties of regulatory T cells (Treg). The aim of this study was to elucidate the role of Treg by applying superagonistic anti-CD28 antibody expansion of Treg. Stroke outcome, thrombus formation, and brain-infiltrating cells were determined on day 1 after transient middle cerebral artery occlusion. Antibody-mediated expansion of Treg enhanced stroke size and worsened functional outcome. Mechanistically, Treg increased thrombus formation in the cerebral microvasculature. These findings confirm that Treg promote thrombo-inflammatory lesion growth during the acute stage of ischemic stroke.

scholarly journals The Paradox Role of Regulatory T Cells in Ischemic Stroke

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Xiaomeng Xu ◽  
Min Li ◽  
Yongjun Jiang
Keyword(s):  
T Cells ◽  
Ischemic Stroke ◽  
Regulatory T Cells ◽  
Microvascular Dysfunction ◽  
Underlying Mechanism ◽  
Pathophysiological Process ◽  
Function Recovery ◽  
Current Lines ◽  
Lines Of Evidence

The underlying mechanism of ischemic stroke is not completely known. Regulatory T cells (Tregs), a subset of T cells, play a pivotal role in the pathophysiological process of ischemic stroke. However, there is also controversy over the role of Tregs in stroke. Hence, the function of Tregs in ischemic stroke has triggered a heated discussion recently. In this paper, we reviewed the current lines of evidence to describe the full view of Tregs in stroke. We would like to introduce the basic concepts of Tregs and then discuss their paradox function in ischemic stroke. On one side, Tregs could protect brain against ischemic injury via modulating the inflammation process. On the other side, they exaggerated the insult by causing microvascular dysfunction. They also interfered with the neurological function recovery. In addition, the reasons for this paradox role would be discussed in the review and the prospective of the clinical application of Tregs was also included. In conclusion, Tregs contributed to the outcome of ischemic stroke, while more lines of evidence are needed to understand how Tregs regulate the immune system and influence the outcome of stroke.

Abstract 3856: Adoptive Transfer Of Regulatory T Cells Confers Long Term Neuroprotection Against Cerebral Ischemic Stroke

Stroke ◽  
2012 ◽  
Vol 43 (suppl_1) ◽  
Author(s):  
Peiying Li ◽  
Xiaoming Hu ◽  
Yu Gan ◽  
Feng Zhang ◽  
Yanqin Gao ◽  
...  
Keyword(s):  
T Cells ◽  
Ischemic Stroke ◽  
Regulatory T Cells ◽  
Infarct Volume ◽  
The Body ◽  
Neurological Deficits ◽  
Adoptive Therapy ◽  
Ischemic Brain ◽  
Cell Based Therapy

Stroke is the leading cause of serious long-term disability in adults. Activation and mobilization of CD4+CD25+ regulatory T cells (Tregs) is an intrinsic mechanism the body uses to restrict pro-inflammatory response, one of the well-established contributing factors for secondary neuronal injury and long-term neurological deficits after stroke. The current study explores the protective effect of Tregs adoptive therapy against post-ischemic brain damage and investigated the mechanisms underlying the action of Tregs. Using a mouse model of focal transient ischemia, we found that intravenous injections of Tregs (2 x 10 6 /animal) within 24 hours (2, 6, and 24 hours) after ischemia resulted in marked reduction of brain infarct. The maximal protection occurred upon earlier Tregs transfer with 2-hour delay after MCAO, which resulted in approximately 30% reduction of infarct volume. Post-ischemic sensorimotor dysfunction significantly improved during both the acute and late recovery after MCAO in Treg-treated mice as assessed by corner test, forelimb placing and cylinder test up to 28 days after ischemic stroke. Furthermore, Tregs treatment inhibited the up-regulation of IL-6, IL-1β, IL-17 and TNF-α in the ischemic brain and mitigated the cerebral infiltration of peripheral immune cells, including neutrophil, macrophage and T cells early after MCAO. Taken together, our study demonstrates that adoptive therapy with Tregs is a novel and potent cell-based therapy targeting post-stroke inflammatory dysregulation.

scholarly journals The Role of Edema in Subacute Lesion Progression After Treatment of Acute Ischemic Stroke

2021 ◽  
Vol 12 ◽  
Author(s):  
Praneeta Konduri ◽  
Katinka van Kranendonk ◽  
Anna Boers ◽  
Kilian Treurniet ◽  
Olvert Berkhemer ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Functional Outcome ◽  
Water Uptake ◽  
Infarct Volume ◽  
Lesion Volume ◽  
Ischemic Lesion ◽  
Contrast Ct ◽  
Mr Clean

Background: Ischemic lesions commonly continue to progress even days after treatment, and this lesion growth is associated with unfavorable functional outcome in acute ischemic stroke patients. The aim of this study is to elucidate the role of edema in subacute lesion progression and its influence on unfavorable functional outcome by quantifying net water uptake.Methods: We included all 187 patients from the MR CLEAN trial who had high quality follow-up non-contrast CT at 24 h and 1 week. Using a CT densitometry-based method to calculate the net water uptake, we differentiated total ischemic lesion volume (TILV) into edema volume (EV) and edema-corrected infarct volume (ecIV). We calculated these volumes at 24 h and 1 week after stroke and determined their progression in the subacute period. We assessed the effect of 24-h lesion characteristics on EV and ecIV progression. We evaluated the influence of edema and edema-corrected infarct progression on favorable functional outcome after 90 days (modified Rankin Scale: 0–2) after correcting for potential confounders. Lastly, we compared these volumes between subgroups of patients with and without successful recanalization using the Mann–Whitney U-test.Results: Median TILV increased from 37 (IQR: 18–81) ml to 68 (IQR: 30–130) ml between 24 h and 1 week after stroke, while the net water uptake increased from 22 (IQR: 16–26)% to 27 (IQR: 22–32)%. The TILV progression of 20 (8.8–40) ml was mostly caused by ecIV with a median increase of 12 (2.4–21) ml vs. 6.5 (2.7–15) ml of EV progression. Larger TILV, EV, and ecIV volumes at 24 h were all associated with more edema and lesion progression. Edema progression was associated with unfavorable functional outcome [aOR: 0.53 (0.28–0.94) per 10 ml; p-value: 0.05], while edema-corrected infarct progression showed a similar, non-significant association [aOR: 0.80 (0.62–0.99); p-value: 0.06]. Lastly, edema progression was larger in patients without successful recanalization, whereas ecIV progression was comparable between the subgroups.Conclusion: EV increases in evolving ischemic lesions in the period between 1 day and 1 week after acute ischemic stroke. This progression is larger in patients without successful recanalization and is associated with unfavorable functional outcome. However, the extent of edema cannot explain the total expansion of ischemic lesions since edema-corrected infarct progression is larger than the edema progression.

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