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  • Online Resource  (5)
  • SAGE Publications  (5)
  • 1
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    Online Resource
    Fight INflammation to Improve outcome after aneurysmal Subarachnoid HEmorRhage (FINISHER) trial: Study protocol for a randomized controlled trial
    SAGE Publications ; 2023
    In:  International Journal of Stroke Vol. 18, No. 2 ( 2023-02), p. 242-247
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    In: International Journal of Stroke, SAGE Publications, Vol. 18, No. 2 ( 2023-02), p. 242-247
    Abstract: Aneurysmal subarachnoid hemorrhage (SAH) has high morbidity and mortality. While the primary injury results from the initial bleeding cannot currently be influenced, secondary injury through vasospasm and delayed cerebral ischemia worsens outcome and might be a target for interventions to improve outcome. To date, beside the aneurysm treatment to prevent re-bleeding and the administration of oral nimodipine, there is no therapy available, so novel treatment concepts are needed. Evidence suggests that inflammation contributes to delayed cerebral ischemia and poor outcome in SAH. Some studies suggest a beneficial effect of anti-inflammatory glucocorticoids, but there are no data from randomized controlled trials examining the efficacy of glucocorticoids. Therefore, current guidelines do not recommend the use of glucocorticoids in SAH. Aim: The Fight INflammation to Improve outcome after aneurysmal Subarachnoid HEmorRhage (FINISHER) trial aims to determine whether dexamethasone improves outcome in a clinically relevant endpoint in SAH patients. Methods and design: FINISHER is a multicenter, prospective, randomized, double-blinded, placebo-controlled clinical phase III trial which is testing the outcome and safety of anti-inflammatory treatment with dexamethasone in SAH patients. Sample size estimates: In all, 334 patients will be randomized to either dexamethasone or placebo within 48 h after SAH. The dexamethasone dose is 8 mg tds for days 1–7 and then 8 mg od for days 8–21. Study outcome: The primary outcome is the modified Rankin Scale (mRS) at 6 months, which is dichotomized to favorable (mRS 0–3) versus unfavorable (mRS 4–6). Discussion: The results of this study will provide the first phase III evidence as to whether dexamethasone improves outcome in SAH.
    Type of Medium: Online Resource
    ISSN: 1747-4930 , 1747-4949
    URL: Article
    DOI: 10.1177/17474930221093501
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2023
    detail.hit.zdb_id: 2211666-7
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  • 2
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    Online Resource
    Endothelial Progenitor Cells Augment Collateralization and Hemodynamic Rescue in a Model of Chronic Cerebral Ischemia
    SAGE Publications ; 2014
    In:  Journal of Cerebral Blood Flow & Metabolism Vol. 34, No. 8 ( 2014-08), p. 1297-1305
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    In: Journal of Cerebral Blood Flow & Metabolism, SAGE Publications, Vol. 34, No. 8 ( 2014-08), p. 1297-1305
    Abstract: Surgical flow augmentation for treatment of cerebral hemodynamic impairment remains controversial. Here, we investigated the benefit of endothelial progenitor cell (EPC) treatment in a rat model of chronic cerebral hypoperfusion. At repeated time points after 3-vessel occlusion (3-VO), animals were treated with 1 × 10 6 Dil-labeled (a) ex vivo-expanded embryonic-EPC (e-EPC), (b) cyclic AMP-differentiated embryonic-endothelial progenitor-derived cells (e-EPDC as biologic control) or, (c) saline. The cerebrovascular reserve capacity (CVRC) was assessed immediately before and on days 7 and 21 after 3-VO. Structural effects were assessed by latex perfusion, immunohistochemistry, and intravital fluorescence video microscopy on day 21. Three-vessel occlusion resulted in a significant impairment of the CVRC with better functional recovery after treatment with e-EPC (16.4 ± 8%) compared with e-EPDC (3.7 ± 8%) or saline (6.4 ± 9%) by day 21 ( P 〈 0.05), which was paralleled by a significant increase in the vessel diameters of the anterior Circle of Willis, a significantly higher number of leptomeningeal anastomoses and higher parenchymal capillary density in e-EPC-treated animals. Interestingly, despite in vivo interaction of e-EPC with the cerebral endothelium, e-EPC incorporation into the cerebral vasculature was not observed. Our results suggest that EPC may serve as a novel therapeutic agent in clinical trials for nonsurgical treatment of chronic cerebral hemodynamic impairment.
    Type of Medium: Online Resource
    ISSN: 0271-678X , 1559-7016
    URL: Article
    DOI: 10.1038/jcbfm.2014.78
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2014
    detail.hit.zdb_id: 2039456-1
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  • 3
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    Autocrine release of angiopoietin-2 mediates cerebrovascular disintegration in Moyamoya disease
    SAGE Publications ; 2017
    In:  Journal of Cerebral Blood Flow & Metabolism Vol. 37, No. 4 ( 2017-04), p. 1527-1539
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    In: Journal of Cerebral Blood Flow & Metabolism, SAGE Publications, Vol. 37, No. 4 ( 2017-04), p. 1527-1539
    Abstract: Moyamoya disease is a rare steno-occlusive cerebrovascular disorder often resulting in hemorrhagic and ischemic strokes. Although sharing the same ischemic stimulus with atherosclerotic cerebrovascular disease, Moyamoya disease is characterized by a highly instable cerebrovascular system which is prone to rupture due to pathological neovascularization. To understand the molecular mechanisms underlying this instability, angiopoietin-2 gene expression was analyzed in middle cerebral artery lesions obtained from Moyamoya disease and atherosclerotic cerebrovascular disease patients. Angiopoietin-2 was significantly up-regulated in Moyamoya vessels, while serum concentrations of soluble angiopoietins were not changed. For further evaluations, cerebral endothelial cells incubated with serum from these patients in vitro were applied. In contrast to atherosclerotic cerebrovascular disease serum, Moyamoya disease serum induced an angiopoietin-2 overexpression and secretion, accompanied by loss of endothelial integrity. These effects were absent or inverse in endothelial cells of non-brain origin suggesting brain endothelium specificity. The destabilizing effects on brain endothelial cells to Moyamoya disease serum were partially suppressed by the inhibition of angiopoietin-2. Our findings define brain endothelial cells as the potential source of vessel-destabilizing factors inducing the high plasticity state and disintegration in Moyamoya disease in an autocrine manner. We also provide new insights into Moyamoya disease pathophysiology that may be helpful for preventive treatment strategies in future.
    Type of Medium: Online Resource
    ISSN: 0271-678X , 1559-7016
    URL: Article
    DOI: 10.1177/0271678X16658301
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2017
    detail.hit.zdb_id: 2039456-1
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  • 4
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    Imaging of Hypoxic–Ischemic Penumbra with 18 F-fluoromisonidazole PET/CT and Measurement of Related Cerebral Metabolism in Aneurysmal Subarachnoid Hemorrhage
    SAGE Publications ; 2010
    In:  Journal of Cerebral Blood Flow & Metabolism Vol. 30, No. 1 ( 2010-01), p. 36-45
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    In: Journal of Cerebral Blood Flow & Metabolism, SAGE Publications, Vol. 30, No. 1 ( 2010-01), p. 36-45
    Abstract: This study aimed to characterize hypoxic, but salvageable, tissue imaged by 18 F-fluoromisonidazole ( 18 F-FMISO), combining with perfusion-computed tomography (PCT) for regional cerebral blood flow (rCBF) measurement and metabolism by microdialysis (MD) in aneurysmal subarachnoidal hemorrhage (SAH) patients. 18 F-FMISO positron-emission tomography (PET)/CT was performed within the period of possible vasospasm (day 6.8±3 after SAH) in seven SAH patients. In parallel, rCBF was determined within the MD region of interest (MD-ROI) ( n=5). The MD catheter was inserted into the brain parenchyma with highest risk for ischemia; extracellular levels of glutamate and energy metabolites were registered at time of PET and hourly for 10 days. Twelve-month outcome was evaluated. In asymptomatic patients ( n=3) no hypoxia was detected and glutamate levels were low ( 〈 10 mmol/L), whereas symptomatic patients had higher glutamate concentrations ( P 〈 0.001). Increased 18 F-FMISO uptake within the MD-ROI ( n=3) was related to higher glutamate levels, while rCBF was above the ischemic range. Hypoxia (increased 18 F-FMISO uptake) was present in symptomatic patients and associated with relevant metabolic derangement of extracellular glutamate levels, whereas energy metabolism and rCBF were preserved. This technique has the potential to improve our understanding of the role of cellular hypoxia in aneurysmal SAH.
    Type of Medium: Online Resource
    ISSN: 0271-678X , 1559-7016
    URL: Article
    DOI: 10.1038/jcbfm.2009.199
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2010
    detail.hit.zdb_id: 2039456-1
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  • 5
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    Clinical Implications of Cortical Microvasculature in Adult Moyamoya Disease
    SAGE Publications ; 2009
    In:  Journal of Cerebral Blood Flow & Metabolism Vol. 29, No. 8 ( 2009-08), p. 1383-1387
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    In: Journal of Cerebral Blood Flow & Metabolism, SAGE Publications, Vol. 29, No. 8 ( 2009-08), p. 1383-1387
    Abstract: We analyzed cortical microvascular parameters using intraoperative ICG (Indocyaninegreen)-Videoangiography in 13 patients with Moyamoya disease, and carried out correlative studies by comparing them with clinical parameters obtained by digital subtraction angiography, physical examination, and regional cerebral blood flow studies. Patients with reduced cerebrovascular reserve capacity were characterized by increased microvascular surface area (MVSA). In addition, MVSA correlated positively with arterial microvascular transit time. Asymptomatic patients were characterized by increased arterial microvascular transit time. We show that patients with a higher arteriogenic potential to alter cortical microvasculature are characterized by a more favorable hemodynamic situation and reduced clinical symptoms.
    Type of Medium: Online Resource
    ISSN: 0271-678X , 1559-7016
    URL: Article
    DOI: 10.1038/jcbfm.2009.69
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2009
    detail.hit.zdb_id: 2039456-1
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