scholarly journals GSK-3β inhibitor TWS119 attenuates rtPA-induced hemorrhagic transformation and activates the Wnt/β-catenin signaling pathway after acute ischemic stroke in rats

2015 ◽  
Vol 53 (10) ◽  
pp. 7028-7036 ◽  
Author(s):  
Wei Wang ◽  
Mingchang Li ◽  
Yuefei Wang ◽  
Qian Li ◽  
Gang Deng ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Signaling Pathway ◽  
Hemorrhagic Transformation ◽  
Gsk 3Β

IM-12 activates the Wnt–β-catenin signaling pathway and attenuates rtPA-induced hemorrhagic transformation in rats after acute ischemic stroke

2019 ◽  
Vol 97 (6) ◽  
pp. 702-708 ◽  
Author(s):  
Ting Wang ◽  
Yu-Mei Duan ◽  
Qiao Fu ◽  
Tao Liu ◽  
Jin-Cheng Yu ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Signaling Pathway ◽  
Glycogen Synthase ◽  
Hemorrhagic Transformation ◽  
Neurological Deficits ◽  
Control Group ◽  
High Morbidity ◽  
Sprague Dawley ◽  
Gsk 3Β

Hemorrhagic transformation (HT) is a devastating complication for patients with acute ischemic stroke (AIS) who are treated with tissue plasminogen activator (tPA). HT is associated with high morbidity and mortality, but no effective treatments are currently available to reduce the risk of HT. Therefore, methods to prevent HT are urgently needed. In this study, we used IM-12, an inhibitor of glycogen synthase kinase 3β (GSK-3β), to evaluate the role of the Wnt–β-catenin signaling pathway in recombinant tPA (rtPA)-induced HT. Sprague–Dawley rats were subjected to a middle cerebral artery occlusion (MCAO) model of ischemic stroke, and then were either administered rtPA, rtPA combined with IM-12, or the vehicle at 4 h after stroke was induced. Our results indicate that rats subjected to HT had more severe neurological deficits, brain edema, and blood–brain barrier (BBB) breakdown, and had a greater infarction volume than the control group. Rats treated with IM-12 had improved outcomes compared with those of rats treated with rtPA alone. Moreover, IM-12 increased the protein expression of β-catenin and downstream proteins while suppressing the expression of GSK-3β. These results suggest that IM-12 reduces rtPA-induced HT and attenuates BBB disruption, possibly through activation of the Wnt–β-catenin signaling pathway, and provides a potential therapeutic strategy for preventing tPA-induced HT after AIS.

scholarly journals Stress hyperglycemia as a prognostic factor in acute ischemic stroke patients: a prospective observational cohort study

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Hanaa A. El-Gendy ◽  
Mahmoud A. Mohamed ◽  
Amr E. Abd-Elhamid ◽  
Mohammed A. Nosseir
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Prognostic Value ◽  
Area Under The Curve ◽  
Hemorrhagic Transformation ◽  
Diabetic Patients ◽  
Stroke Patients ◽  
Stress Hyperglycemia ◽  
Discrimination Power ◽  
Observational Cohort

Abstract Background Hyperglycemia is a risk factor for infarct expansion and poor outcome for both diabetic and non-diabetic patients. We aimed to study the prognostic value of stress hyperglycemia on the outcome of acute ischemic stroke patients as regards National Institutes of Health Stroke Scale (NIHSS) as a primary outcome. Results Patients with high random blood sugar (RBS) on admission showed significantly higher values of both median NIHSS score and median duration of hospital stay. There were significant associations between stress hyperglycemia and the risk of 30-day mortality (p < 0.001), the need for mechanical ventilation (p < 0.001) and vasopressors (p < 0.001), and the occurrence of hemorrhagic transformation (p = 0.001). The 24-h RBS levels at a cut off > 145 mg/dl showed a significantly good discrimination power for 30-day mortality (area under the curve = 0.809). Conclusions Stress hyperglycemia had a prognostic value and was associated with less-favorable outcomes of acute stroke patients. Therefore, early glycemic control is recommended for those patients.

CKD is associated with recurrent ischemia but not with hemorrhagic transformation in acute ischemic stroke patients

Renal Failure ◽  
2013 ◽  
Vol 36 (2) ◽  
pp. 217-221 ◽  
Author(s):  
Hasan Micozkadioglu ◽  
Ruya Ozelsancak ◽  
Semih Giray ◽  
Zulfikar Arlier
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Hemorrhagic Transformation ◽  
Stroke Patients ◽  
Recurrent Ischemia

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.

Abstract P12: Alteplase Reduces Mortality in Patients With Ischemic Stroke and Atrial Fibrillation: Analysis of the IAC Study

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Shadi Yaghi ◽  
Eva Mistry ◽  
Adam H De Havenon ◽  
Christopher Leon Guerrero ◽  
Amre Nouh ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Infarct Volume ◽  
Intravenous Thrombolysis ◽  
The United States ◽  
Hemorrhagic Transformation ◽  
Stroke Patients ◽  
Increased Risk ◽  
Significant Difference

Background and Purpose: Multiple studies have established that intravenous thrombolysis with alteplase improves outcome after acute ischemic stroke. However, assessment of thrombolysis’ efficacy in stroke patients with atrial fibrillation (AF) has yielded mixed results. We sought to determine the association of alteplase with mortality, hemorrhagic transformation (HT), infarct volume, and mortality in patients with AF and acute ischemic stroke. Methods: We retrospectively analyzed consecutive acute ischemic stroke patients with AF included in the Initiation of Anticoagulation after Cardioembolic stroke (IAC) study, which pooled data from 8 comprehensive stroke centers in the United States. 1889 (90.6%) had available 90-day follow up data and were included. For our primary analysis we used a cohort of 1367/1889 (72.4%) patients who did not undergo mechanical thrombectomy (MT). Secondary analyses were repeated in the patients that underwent MT (n=522). Binary logistic regression was used to determine whether alteplase use was independently associated with risk of HT, final infarct volume, and 90-day mortality, respectively, adjusting for potential confounders. Results: In our primary analyses we found that alteplase use was independently associated with an increased risk for HT (adjusted OR 2.14, 95% CI 1.49 - 3.07, p <0.001) but overall reduced risk of 90-day mortality (adjusted OR 0.58, 95% CI 0.39 - 0.87, p = 0.009). Among patients undergoing MT, alteplase use was associated with a trend towards a reduction in 90-day mortality (adjusted OR 0.68 95% CI 0.45 - 1.04, p = 0.077). In the subgroup of patients prescribed DOAC treatment (n = 327; 24 received alteplase), alteplase treatment was associated with a trend towards smaller infarct size (< 10 mL), (adjusted OR 0.40, 95% CI 0.15 - 1.12, p = 0.082) without a significant difference in the odds of 90-day mortality (adjusted OR 0.51, 95% CI 0.12 - 2.13, p = 0.357) or hemorrhagic transformation (adjusted OR 0.27, 95% CI 0.03 - 2.07, p = 0.206). Conclusion: Thrombolysis with intravenous alteplase was associated with reduced 90-day mortality in AF patients with acute ischemic stroke not undergoing MT. Further study is required to assess the safety and efficacy of alteplase in AF patients undergoing MT and those on DOACs.

Abstract TP315: D-dimer is Associated With 30-day Mortality in Acute Ischemic Stroke With Active Cancer

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Ki Woong Nam ◽  
Chi Kyung Kim ◽  
Tae Jung Kim ◽  
Sang Joon An ◽  
Kyungmi Oh ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Infarct Volume ◽  
Hemorrhagic Transformation ◽  
Stroke Patients ◽  
Nihss Score ◽  
Patients With Cancer ◽  
Advanced Stages ◽  
D Dimer ◽  
Active Cancer

Background: Stroke in cancer patients is not rare, but is a devastating event with high mortality. However, the predictors of mortality in stroke patients with cancer have not been well addressed. D-dimer could be a useful predictor because it can reflect both thromboembolic events and advanced stages of cancer. In this study, we evaluate the possibility of D-dimer as a predictor of 30-day mortality in stroke patients with active cancer. Methods: We included 210 ischemic stroke patients with active cancer. The data of 30-day mortality were collected by reviewing medical records. We also collected follow-up D-dimer levels in 106 (50%) participants to evaluate the effects of treatment response on D-dimer levels. Results: Of the 210 participants, 30-day mortality occurred in 28 (13%) patients. Higher initial NIHSS score, D-dimer levels, CRP levels, frequent cryptogenic mechanism, systemic metastasis, multiple vascular territory lesion, hemorrhagic transformation, and larger infarct volume were related to 30-day mortality. In the multivariate analysis, D-dimer [adjusted OR (aOR) = 2.19; 95% CI, 1.46-3.28, P < 0.001] predicted 30-day mortality after adjusting for confounders. Initial NIHSS score (aOR = 1.07; 95% CI, 1.00-1.14, P = 0.043) and hemorrhagic transformation (aOR = 3.02; 95% CI, 1.10-8.29, P = 0.032) were also significant independently from D-dimer levels. In the analysis of D-dimer changes after treatment, the mortality group showed no significant decrease of D-dimer levels, despite treatment, while the survivor group showed opposite responses. Conclusions: D-dimer levels may predict 30-day mortality in acute ischemic stroke patients with active cancer.

Abstract W P63: Intravenous Thrombolysis for Acute Ischemic Stroke in Nonagenarians

Stroke ◽  
2015 ◽  
Vol 46 (suppl_1) ◽  
Author(s):  
Raul Guisado ◽  
Reza Malek ◽  
Ursula Kelly-Tolley ◽  
Arash Padidar ◽  
Harmeet Sachdev
Keyword(s):  
Ischemic Stroke ◽  
Mortality Rate ◽  
Acute Ischemic Stroke ◽  
Ct Perfusion ◽  
Intravenous Thrombolysis ◽  
Hemorrhagic Transformation ◽  
Early Improvement ◽  
Hospital Patients ◽  
Contrast Ct ◽  
Overall Mortality

The safety and effectiveness of intravenous thrombolysis for acute ischemic stroke (AIS) has been established for populations older than 80 years of age . However, management of AIS in nonagenerians is not clear. Previous reports suggest that the rate of ICH after i.v. alteplase is not increased and the rate of early improvement is similar in nonagenerians compared to younger groups, but there is concern with overall mortality and functional outcomes. We report on 20 consecutive patients with AIS treated with i.v. alteplase within 3 hours of onset in two Comprehensive Stroke Centers in San Jose, CA. Methods: Patients were immediately evaluated by members of the Stroke Team of each hospital. . Patients were eligible if they had disabling neurological symptoms, no contraindications for i.v.alteplase and were independent in ADLs prior to the index event. Non-contrast CT brain scan, CT perfusion and CT angiography of head and neck were used to determine the presence of potentially salvageable brain. Results (Table): Mean age was 91 years (range 90 - 98 years). The initial NIHSS was 15.7 ± 6.8. The median NIHSS at hospital discharge was 7.4 ± 8.4 (p <0.001). The median door to needle time was 50.5 minutes (range 36 - 74 minutes). There was no hemorrhagic transformation and no in-hospital mortality. The overall mortality rate at 90 days was 30% (6 of 20 patients) and the rate of good outcome in survivors, defined as mRS ≤ 3 at 90 days was 35.7% (5 of 14 patients). Comment: Intravenous thrombolysis for ischemic stroke in nonagenerians is safe and effective, with good rates of immediate improvement. However, the l90 days mortality rate is high and the long term functional outcome is poor. This data can be useful in helping families make treatment decisions in the most elderly patients with acute ischemic stroke.

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