MRI Blood–Brain Barrier Permeability Measurements to Predict Hemorrhagic Transformation in a Rat Model of Ischemic Stroke

2012 ◽  
Vol 3 (4) ◽  
pp. 508-516 ◽  
Author(s):  
Angelika Hoffmann ◽  
Jörg Bredno ◽  
Michael F. Wendland ◽  
Nikita Derugin ◽  
Jason Hom ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Blood Brain Barrier ◽  
Rat Model ◽  
Hemorrhagic Transformation ◽  
Brain Barrier ◽  
Barrier Permeability ◽  
Blood Brain Barrier Permeability ◽  
Blood Brain ◽  
Brain Barrier Permeability

Abstract 2792: Bone Marrow Mononuclear Cells Improve Blood-Brain Barrier Permeability And Decrease Hemorrhagic Transformation After Treatment With Tissue Plasminogen Activator In An Embolic Stroke Model

Stroke ◽  
2012 ◽  
Vol 43 (suppl_1) ◽  
Author(s):  
Bing Yang ◽  
Xiaopei Xi ◽  
Sean.I Savitz
Keyword(s):  
Bone Marrow ◽  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Blood Brain Barrier ◽  
Hemorrhagic Transformation ◽  
Brain Barrier ◽  
Barrier Permeability ◽  
Blood Brain Barrier Permeability ◽  
Blood Brain ◽  
Brain Barrier Permeability

Background: Tissue plasminogen activator (t-PA) is the only treatment approved in the US for acute ischemic stroke. Cell-based therapies are being studied as a new investigational treatment approach for stroke but few studies have assessed the interaction of cell therapies with IV t-PA in an embolic model. Our laboratory has been investigating the therapeutic potential of bone marrow mononuclear cells (MNCs), which have been shown to enhance recovery after acute ischemic stroke and are currently being studied in safety clinical trials. Methods: An embolic ischemic stroke model was established by deposition of an autologous blood clot into the internal carotid artery in adult Long Evans rats. IV t-PA (10 mg/kg) was administered at 1 hour after occlusion. Two hours later, 10 million allogeneic MNCs per kilogram or saline were given intravenously (N=12 per group). Hemorrhagic transformation (HT) and blood-brain barrier permeability using Evans Blue were quantified at 3 days after stroke. In an in vitro study, astrocytes were isolated from postnatal P1 rats, pre-conditioned by oxygen-glucose deprivation (OGD) for 45 min, and then cultured with MNCs derived from the mother’s bone marrow. MMP-3 was assayed in the media. Results: Over 40% (42%) of animals treated with t-PA had HT at 3 days after stroke. The incidence of HT did not differ in the MNC and saline treated groups. However, the ICH scores were significantly reduced in the MNC group (2±1.2) compared to saline controls (3.8±0.8) ( Fig A, p =0.027). BBB permeability was also reduced in the MNC group (0.28±0.07) compared to saline controls (0.6±0.12) ( Fig B, p =0.033). In the in vitro study, MMP-3 levels in the medium of cultured pre-conditioned astrocytes (30.6±3.7 ng/ml) were reduced when co-cultured directly with MNCs (23.1±2.0 ng/ml, p =0.047) but MMP-3 levels were unchanged when astrocytes and MNCs were co-cultured in transwell (32.8±3.2 ng/ml) ( Fig C&D). Conclusion: We have found for the first time that bone marrow derived MNCs reduce hemorrhagic transformation and blood brain barrier permeability after treatment with IV t-PA for acute ischemic stroke. Our results suggest a novel mechanism in which MNCs may attenuate hemorrhagic risk from t-PA by reducing the release of MMP-3 from astrocytes.

scholarly journals Cytokine MIF Enhances Blood-Brain Barrier Permeability: Impact for Therapy in Ischemic Stroke

2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Yu-Chuan Liu ◽  
Yung-Hsu Tsai ◽  
Sung-Chun Tang ◽  
Houng-Chi Liou ◽  
Kai-Hsiang Kang ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Barrier Permeability ◽  
Blood Brain Barrier Permeability ◽  
Blood Brain ◽  
Brain Barrier Permeability

scholarly journals Computed Tomography Perfusion Derived Blood-Brain Barrier Permeability Does Not Yet Improve Prediction of Hemorrhagic Transformation

2018 ◽  
Vol 45 (1-2) ◽  
pp. 26-32 ◽  
Author(s):  
Alexander D. Horsch ◽  
Edwin Bennink ◽  
Tom van Seeters ◽  
L. Jaap Kappelle ◽  
Yolanda van der Graaf ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Blood Brain Barrier ◽  
Hemorrhagic Transformation ◽  
Brain Barrier ◽  
Barrier Permeability ◽  
Blood Brain Barrier Permeability ◽  
Blood Brain ◽  
Increased Risk ◽  
Brain Barrier Permeability

Introduction: Hemorrhagic transformation (HT) in acute ischemic stroke can occur as a result of reperfusion treatment. While withholding treatment may be warranted in patients with increased risk of HT, prediction of HT remains difficult. Nonlinear regression analysis can be used to estimate blood-brain barrier permeability (BBBP). The aim of this study was to identify a combination of clinical and imaging variables, including BBBP estimations, that can predict HT. Materials and Methods: From the Dutch acute stroke study, 545 patients treated with intravenous recombinant tissue plasminogen activator and/or intra-arterial treatment were selected, with available admission extended computed tomography (CT) perfusion and follow-up imaging. Patient admission treatment characteristics and CT imaging parameters regarding occlusion site, stroke severity, and BBBP were recorded. HT was assessed on day 3 follow-up imaging. The association between potential predictors and HT was analyzed using univariate and multivariate logistic regression. To compare the added value of BBBP, areas under the curve (AUCs) were created from 2 models, with and without BBBP. Results: HT occurred in 57 patients (10%). In univariate analysis, older age (OR 1.03, 95% CI 1.006–1.05), higher admission National Institutes of Health Stroke Scale (NIHSS; OR 1.13, 95% CI 1.08–1.18), higher clot burden (OR 1.28, 95% CI 1.16–1.41), poor collateral score (OR 3.49, 95% CI 1.85–6.58), larger Alberta Stroke Program Early CT Score cerebral blood volume deficit size (OR 1.26, 95% CI 1.14–1.38), and increased BBBP (OR 2.22, 95% CI 1.46–3.37) were associated with HT. In multivariate analysis with age and admission NIHSS, the addition of BBBP did not improve the AUC compared to both independent predictors alone (AUC 0.77, 95% CI 0.71–0.83). Conclusion: BBBP predicts HT but does not improve prediction with age and admission NIHSS.

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