NADPH oxidase inhibitor regulates microRNAs with improved outcome after mechanical reperfusion

2016 ◽  
Vol 9 (7) ◽  
pp. 702-706 ◽  
Author(s):  
Zhong Liu ◽  
Yong-Hua Tuo ◽  
Jian-Wen Chen ◽  
Qing-Yuan Wang ◽  
Songlin Li ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Nadph Oxidase ◽  
Acute Ischemic Stroke ◽  
Infarct Volume ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Hemorrhagic Transformation ◽  
Oxidase Inhibitor ◽  
Rt Pcr ◽  
Stroke Treatment ◽  
Microrna Microarray

BackgroundInhibition of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) pathway improves the neurological outcome in the transient middle cerebral artery occlusion (tMCAO) animal model. In this study we analyzed the microRNAs profile targeting NOX2 and NOX4 genes and its response to NOX2/4 inhibitor VAS2870 to understand the mechanisms of this protective effect.MethodsThe intraluminal filament tMCAO model was established in hyperglycemic rats (n=106) with 5 hours ischemia followed by 19 hours reperfusion. NOX inhibitor VAS2870 was delivered intravenously before reperfusion. Infarct volume, hemorrhagic transformation, and mortality were determined at 24 hours after cerebral ischemia. MicroRNAs profile targeting NOX2 and NOX4 genes were predicted by microRNA databases and further evaluated by microRNA microarray and quantitative RT-PCR.ResultsTen microRNAs potentially targeting NOX2 and NOX4 genes (including microRNA-29a, microRNA-29c, microRNA-126a, microRNA-132, microRNA-136, microRNA-138, microRNA-139, microRNA-153, microRNA-337, and microRNA-376a) were significantly downregulated in the ischemic hemisphere in the tMCAO group compared with the sham-operated group, as shown by microRNA microarray and quantitative RT-PCR (all p<0.05). Intravenous treatment with NOX inhibitor VAS2870 before reperfusion increased the expression of microRNA-29a, microRNA-29c, microRNA-126a, and microRNA-132 compared with the tMCAO group (all p<0.05).ConclusionsSeveral microRNAs potentially targeting NOX2 and NOX4 genes displayed altered levels in hyperglycemic rats with the tMCAO model, suggesting their regulatory roles and targeting potentials for acute ischemic stroke treatment. Targeting specific microRNAs may represent a novel intervention opportunity to improve outcome and reduce hemorrhagic transformation after mechanical reperfusion for acute ischemic stroke.

NADPH oxidase inhibitor improves outcome of mechanical reperfusion by suppressing hemorrhagic transformation

2016 ◽  
Vol 9 (5) ◽  
pp. 492-498 ◽  
Author(s):  
Yong-Hua Tuo ◽  
Zhong Liu ◽  
Jian-Wen Chen ◽  
Qing-Yuan Wang ◽  
Song-Lin Li ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Nadph Oxidase ◽  
Acute Stroke ◽  
Neuronal Apoptosis ◽  
Mechanical Thrombectomy ◽  
Infarct Volume ◽  
Ischemia Reperfusion ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Hemorrhagic Transformation ◽  
Stroke Treatment

BackgroundSevere hemorrhagic transformation (HT) after mechanical thrombectomy predicts a poor clinical outcome in acute ischemic stroke. To better understand the mechanism of HT, we investigated the role of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) in HT after reperfusion during acute stroke and whether NOX2/4 inhibitor VAS2870 reduces reperfusion-induced HT after mechanical recanalization.MethodsA model of reperfusion-induced HT was established in rats (n=182) with hyperglycemic challenge and 5 h middle cerebral artery occlusion followed by 19 h reperfusion. NOX inhibitor VAS2870 was delivered intravenously 30 min before reperfusion. Infarct volume, brain water content, HT, neurological score, mortality rate, blood–brain barrier (BBB) damage, neuronal apoptosis, and reactive oxygen species were determined at 24 h after cerebral ischemia. The expressions of NOX1, NOX2, NOX4, and BBB-associated proteins were measured.ResultsNOX2 and NOX4 upregulation and severe HT were observed in hyperglycemic rats after cerebral ischemia/reperfusion. VAS2870 suppressed oxidative stress, neuronal apoptosis, and NOX2/4 upregulation in the ischemic hemisphere. VAS2870 reduced infarct volume (17.2±5.3% vs 37.4±9.2%, p<0.01) and the frequency of reperfusion-induced parenchymal hematoma (29.7% vs 59.5%, p<0.05) at 24 h after ischemia compared with the ischemia/reperfusion group. VAS2870 attenuated brain edema and reduced reperfusion-induced BBB breakdown, resulting in improved neurological outcome (neurological deficit score 1.43±0.50 vs 2.43±0.93, p<0.001) and reduced mortality (11.9% vs 64.1%, p<0.001).ConclusionsNOX2 and NOX4 may mediate HT in rats with large vessel stroke after mechanical reperfusion. Infusion of NOX inhibitor VAS2870 before mechanical thrombectomy represents a novel adjunctive therapeutic strategy to prevent reperfusion-induced HT and improve outcome of acute stroke treatment.

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 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 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.

Abstract T P26: Combining Clinical and Imaging Data to Develop a Highly Predictive Model of Outcomes in the MR RESCUE Trial

Stroke ◽  
2015 ◽  
Vol 46 (suppl_1) ◽  
Author(s):  
Chelsea S Kidwell ◽  
Reza Jahan ◽  
Jeffrey Gornbein ◽  
Jeffry R Alger ◽  
Val Nenov ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Infarct Volume ◽  
Patient Characteristics ◽  
Hemorrhagic Transformation ◽  
Imaging Data ◽  
Vascular Events ◽  
Vessel Occlusion ◽  
Intermediate Variables ◽  
Core Volume

Background: Identifying patient characteristics that predict outcomes in acute ischemic stroke may assist in triaging those who are candidates for endovascular therapies. We sought to identify predictors of outcome in the overall Mechanical Retrieval and Recanalization of Stroke Clots Using Embolectomy (MR RESCUE) cohort and compare results to the previously validated Totaled Health Risks in Vascular Events (THRIVE) score. Methods: MR RESCUE randomized 118 acute ischemic stroke patients with multimodal imaging to embolectomy or standard care within 8 hours of onset. For this analysis, we investigated 17 baseline variables (e.g. age, predicted core volume, time to enrollment) and 8 intermediate variables (e.g. hemorrhagic transformation, day 7 recanalization, final infarct volume) with the potential to impact outcomes (day 90 mRS). The baseline variables were analyzed employing bivariate and multivariate methods (random forest and logistic regression). Two models were developed, one including only significant baseline variables, and the second also incorporating significant intermediate variables. Results: A multivariate model (Table) employing only baseline covariates achieved an overall accuracy (C statistic) of 85% in predicting poor outcome (day 90 mRS 3-6) compared to 80.5% for the THRIVE score. A second model (Table) adding significant intermediate variables achieved 89% accuracy in predicting day 90 mRS. Conclusions: In the MR RESCUE trial, advanced imaging variables, including predicted core volume and site of vessel occlusion, contributed to a highly accurate multivariable model of outcome. In the development phase, this model achieved higher accuracy than the THRIVE score. Future studies are needed to validate this model in an independent cohort.

scholarly journals Role of NADPH Oxidase-Induced Hypoxia-Induced Factor-1α Increase in Blood-Brain Barrier Disruption after 2-Hour Focal Ischemic Stroke in Rat

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Yanping Wang ◽  
Yufei Shen ◽  
Xin Yu ◽  
Jingxia Gu ◽  
Xiaoling Zhang ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Nadph Oxidase ◽  
Acute Ischemic Stroke ◽  
Blood Brain Barrier ◽  
Critical Role ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Brain Barrier ◽  
Blood Brain ◽  
Junction Protein

We recently showed that inhibition of hypoxia-induced factor-1α (HIF-1α) decreased acute ischemic stroke-induced blood-brain barrier (BBB) damage. However, factors that induce the upregulation of HIF-1α expression remain unclear. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase played a critical role in reperfusion-induced BBB damage after stroke. However, the role of NADPH oxidase in BBB injury during the acute ischemia stage remains unclear. This study is aimed at investigating the role of NADPH oxidase in BBB injury and the expression of HIF-1α after acute ischemic stroke. A sutured middle cerebral artery occlusion (MCAO) model was used to mimic ischemic stroke in rats. Our results show that the inhibition of NADPH oxidase by apocynin can significantly reduce the BBB damage caused by 2 h ischemic stroke accompanied by reducing the degradation of tight junction protein occludin. In addition, treatment with apocynin significantly decreased the upregulation of HIF-1α induced by 2 h MCAO. More importantly, apocynin could also inhibit the MMP-2 upregulation. Of note, HIF-1α was not colocalized with a bigger blood vessel. Taken together, our results showed that inhibition of NADPH oxidase-mediated HIF-1α upregulation reduced BBB damage accompanied by downregulating MMP-2 expression and occludin degradation after 2 h ischemia stroke. These results explored the mechanism of BBB damage after acute ischemic stroke and may help reduce the associated cerebral hemorrhage transformation after thrombolysis and endovascular treatment after ischemic stroke.

Abstract 177: Risk of Thrombolysis-induced Hemorrhagic Transformation in Patients with Acute Ischemic Stroke: A Predictive Model Using Combined MR Perfusion Biomarkers

Stroke ◽  
2015 ◽  
Vol 46 (suppl_1) ◽  
Author(s):  
Kambiz Nael ◽  
Adam H Bauer ◽  
Chelsea S Kidwell
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Roc Analysis ◽  
Cerebral Blood Volume ◽  
Optimal Parameter ◽  
Infarct Volume ◽  
Probabilistic Method ◽  
Hemorrhagic Transformation ◽  
Mr Perfusion ◽  
Multivariable Logistic Regression Model

Purpose: Hemorrhagic transformation (HT) is a potential devastating complication of thrombolysis in patients with acute ischemic stroke (AIS). The purpose of this study was to evaluate the predictive role of MR perfusion biomarkers including increased microvascular permeability (K2) and decreased cerebral blood volume (CBV) in the infarction core to predict the risk of HT in a cohort of patients with AIS who received thrombolysis. Methods: In this retrospective study, patients were included if they: had AIS, received thrombolysis, had pre-treatment MRI (including diffusion and perfusion) and had follow-up MRI for evaluation of HT within 7 days. MR perfusion data were processed employing a Bayesian probabilistic method. Using coregistered images, voxel-based K2 and rCBV values were obtained in the region of infarction (defined by ADC < 600 10 –6 mm 2 /s) and compared in patients with and without HT. Receiver operating characteristic (ROC) analysis was performed to determine the optimal parameter/s and threshold for predicting HT. Results: Forty-eight patients met study criteria: mean (SD) age was 67.5 ± 15, median baseline NIHSS was 9 (IQR: 5-24) and mean infarct volume of 34 ± 18 ml (range 11-78 ml). Thirty percent of patients (14/48) had HT. The mean K2 value was significantly ( p< . 0001) higher in patients with HT (0.24 ± 0.17) versus patients without HT (0.08 ± 0.03). Mean rCBV was significantly ( p=0 .0001) lower in patients with HT (0.21 ± 0.02) compared to patients without HT (1.28 ± 0.66). ROC analysis showed a threshold and corresponding sensitivity/specificity of 0.104, 94%/84% for K2 and 0.38, 94/97% for rCBV. The combination of K2 and rCBV resulted in a higher discriminative power with an AUC of 0.97, sensitivity of 94% and specificity of 100%. In a multivariable logistic regression model that included NIHSS and infarct volume, the combined K2-rCBV classifier was an independent predictor of HT. Conclusion: Combined increased permeability and decreased CBV derived from MR perfusion have improved sensitivity and specificity, compared to either measure alone, for prediction of HT following thrombolysis. A larger clinical study is required to validate our results in an independent cohort.

scholarly journals Targets of vascular protection in acute ischemic stroke differ in type 2 diabetes

2013 ◽  
Vol 304 (6) ◽  
pp. H806-H815 ◽  
Author(s):  
Aisha I. Kelly-Cobbs ◽  
Roshini Prakash ◽  
Weiguo Li ◽  
Bindu Pillai ◽  
Sherif Hafez ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Infarct Volume ◽  
Hemorrhagic Transformation ◽  
Artery Occlusion ◽  
Neurological Deficits ◽  
Diabetic Patients ◽  
Vascular Protection ◽  
Acute Therapy

Hemorrhagic transformation is an important complication of acute ischemic stroke, particularly in diabetic patients receiving thrombolytic treatment with tissue plasminogen activator, the only approved drug for the treatment of acute ischemic stroke. The objective of the present study was to determine the effects of acute manipulation of potential targets for vascular protection [i.e., NF-κB, peroxynitrite, and matrix metalloproteinases (MMPs)] on vascular injury and functional outcome in a diabetic model of cerebral ischemia. Ischemia was induced by middle cerebral artery occlusion in control and type 2 diabetic Goto-Kakizaki rats. Treatment groups received a single dose of the peroxynitrite decomposition catalyst 5,10,15,20-tetrakis(4-sulfonatophenyl)prophyrinato iron (III), the nonspecific NF-κB inhibitor curcumin, or the broad-spectrum MMP inhibitor minocycline at reperfusion. Poststroke infarct volume, edema, hemorrhage, neurological deficits, and MMP-9 activity were evaluated. All acute treatments reduced MMP-9 and hemorrhagic transformation in diabetic groups. In addition, acute curcumin and minocycline therapy reduced edema in these animals. Improved neurological function was observed in varying degrees with treatment, as indicated by beam-walk performance, modified Bederson scores, and grip strength; however, infarct size was similar to untreated diabetic animals. In control animals, all treatments reduced MMP-9 activity, yet bleeding was not improved. Neuroprotection was only conferred by curcumin and minocycline. Uncovering the underlying mechanisms contributing to the success of acute therapy in diabetes will advance tailored stroke therapies.

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