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Translational Stroke Research

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https://www.readbyqxmd.com/read/28534197/pcmt1-ameliorates-neuronal-apoptosis-by-inhibiting-the-activation-of-mst1-after-subarachnoid-hemorrhage-in-rats
#1
Ligen Shi, Ammar Al-Baadani, Keren Zhou, Anwen Shao, Shenbin Xu, Sheng Chen, Jianmin Zhang
Mammalian sterile 20-like kinase 1 (MST1) is found to promote neuronal apoptosis. Protein-L-isoaspartate (D-aspartate) O-methyltransferase (PCMT1), an anti-apoptosis factor, was recently identified as an MST1-interacting protein. This study aims to explore the potential role of PCMT1 in reducing MST1-induced neuronal apoptosis after subarachnoid hemorrhage (SAH) in rats. One hundred ninety-eight male Sprague-Dawley rats were used. An exogenous PCMT1 agonist, CGP 3466B, was injected subcutaneously 1 h after the SAH induced by endovascular perforation...
May 22, 2017: Translational Stroke Research
https://www.readbyqxmd.com/read/28509283/in-vivo-molecular-mri-of-icam-1-expression-on-endothelium-and-leukocytes-from-subacute-to-chronic-stages-after-experimental-stroke
#2
Lisette H Deddens, Geralda A F van Tilborg, Kajo van der Marel, Hedi Hunt, Annette van der Toorn, Max A Viergever, Helga E de Vries, Rick M Dijkhuizen
Molecular MRI allows in vivo detection of vascular cell adhesion molecules expressed on inflamed endothelium, which enables detection of specific targets for anti-neuroinflammatory treatment. We explored to what extent MR contrast agent targeted to intercellular adhesion molecule-1 (ICAM-1) could detect endothelial- and leukocyte-associated ICAM-1 expression at different stages after experimental stroke. Furthermore, we assessed potential interfering effects of ICAM-1-targeted contrast agent on post-stroke lesion growth...
May 16, 2017: Translational Stroke Research
https://www.readbyqxmd.com/read/28477280/biomarkers-of-acute-stroke-etiology-base-study-methodology
#3
Edward C Jauch, Andrew D Barreto, Joseph P Broderick, Doug M Char, Brett L Cucchiara, Thomas G Devlin, Alison J Haddock, William J Hicks, Brian C Hiestand, Glen C Jickling, Jeff June, David S Liebeskind, Ted J Lowenkopf, Joseph B Miller, John O'Neill, Tim L Schoonover, Frank R Sharp, W Frank Peacock
Acute ischemic stroke affects over 800,000 US adults annually, with hundreds of thousands more experiencing a transient ischemic attack. Emergent evaluation, prompt acute treatment, and identification of stroke or TIA (transient ischemic attack) etiology for specific secondary prevention are critical for decreasing further morbidity and mortality of cerebrovascular disease. The Biomarkers of Acute Stroke Etiology (BASE) study is a multicenter observational study to identify serum markers defining the etiology of acute ischemic stroke...
May 5, 2017: Translational Stroke Research
https://www.readbyqxmd.com/read/28405804/cytoprotective-drug-tissue-plasminogen-activator-protease-interaction-assays-screening-of-two-novel-cytoprotective-chromones
#4
Paul A Lapchak, Jacqueline M Lara, Paul D Boitano
Tissue plasminogen activator (tPA) is currently used in combination with endovascular procedures to enhance recanalization and cerebral reperfusion and is also currently administered as standard-of-care thrombolytic therapy to patients within 3-4.5 h of an ischemic stroke. Since tPA is not neuroprotective or cytoprotective, adjuvant therapy with a neuroprotective or an optimized cytoprotective compound is required to provide the best care to stroke victims to maximally promote clinical recovery. In this article, we describe the use of a sensitive standardized protease assay with CH3SO2-D-hexahydrotyrosine-Gly-Arg-p-nitroanilide•AcOH, a chromogenic protease substrate that is cleaved to 4-nitroaniline (p-nitroaniline) and measured spectrophotometrically at 405 nm (OD405 nm), and how the assay can be used as an effective screening assay to study drug-tPA interactions...
April 12, 2017: Translational Stroke Research
https://www.readbyqxmd.com/read/28386733/cd163-a-hemoglobin-haptoglobin-scavenger-receptor-after-intracerebral-hemorrhage-functions-in-microglia-macrophages-versus-neurons
#5
EDITORIAL
Thomas Garton, Richard F Keep, Ya Hua, Guohua Xi
No abstract text is available yet for this article.
April 6, 2017: Translational Stroke Research
https://www.readbyqxmd.com/read/28386732/translational-stroke-research-guideline-projections-the-20-20-standards
#6
LETTER
Paul A Lapchak, John H Zhang
No abstract text is available yet for this article.
April 6, 2017: Translational Stroke Research
https://www.readbyqxmd.com/read/28378315/preclinical-development-of-a-prophylactic-neuroprotective-therapy-for-the-preventive-treatment-of-anticipated-ischemia-reperfusion-injury
#7
Frances Rena Bahjat, G Alexander West, Steven G Kohama, Christine Glynn, Henryk F Urbanski, Theodore R Hobbs, Eric Earl, Susan L Stevens, Mary P Stenzel-Poore
Ischemia-reperfusion brain injury can be iatrogenically induced secondary to life-saving procedures. Prophylactic treatment of these patients offers a promising prevention for lifelong complications. We postulate that a cytosine-guanine (CpG) oligodeoxynucleotide (ODN) can provide robust antecedent protection against cerebral ischemic injury with minimal release of pro-inflammatory cytokines, making it an ideal candidate for further clinical development. Mouse and nonhuman primate (NHP) models of cerebral ischemic injury were used to test whether an A-type CpG ODN, which induces minimal systemic inflammatory cytokine responses, can provide prophylactic protection...
April 5, 2017: Translational Stroke Research
https://www.readbyqxmd.com/read/28283966/data-standardization-and-quality-management
#8
Paul A Lapchak, John H Zhang
Important questions regarding the conduct of scientific research and data transparency have been raised in various scientific forums over the last 10 years. It is becoming clear, that in spite of published RIGOR guidelines, that improvement in the transparency of scientific research is required to focus on the discovery and drug development process so that a treatment can be provided to stroke patients. We have the unique privilege of conducting research using animal models of a disease so that we can address the development of a new therapy, and we should do this with great care and vigilance...
March 10, 2017: Translational Stroke Research
https://www.readbyqxmd.com/read/28281221/evidence-for-decreased-brain-parenchymal-volume-after-large-intracerebral-hemorrhages-a-potential-mechanism-limiting-intracranial-pressure-rises
#9
Michael R Williamson, Frederick Colbourne
Potentially fatal intracranial pressure (ICP) rises commonly occur after large intracerebral hemorrhages (ICH). We monitored ICP after infusing 100-160 μL of autologous blood (vs. 0 μL control) into the striatum of rats in order to test the validity of this common model with regard to ICP elevations. Other endpoints included body temperature, behavioral impairment, lesion volume, and edema. Also, we evaluated hippocampal CA1 sector and somatosensory cortical neuron morphology to assess whether global ischemic injury occurred...
March 9, 2017: Translational Stroke Research
https://www.readbyqxmd.com/read/28271393/translational-stroke-research-opportunities-and-a-strategy-to-develop-effective-cytoprotection
#10
EDITORIAL
Paul A Lapchak
No abstract text is available yet for this article.
March 8, 2017: Translational Stroke Research
https://www.readbyqxmd.com/read/28265861/re-evaluate-the-efficacy-and-safety-of-human-urinary-kallidinogenase-resk-protocol-for-an-open-label-single-arm-multicenter-phase-iv-trial-for-the-treatment-of-acute-ischemic-stroke-in-chinese-patients
#11
Jun Ni, Jiazhi Qu, Ming Yao, Zhijun Zhang, Xihua Zhong, Liying Cui
Acute ischemic stroke (AIS) is a major medical challenge in China. Thrombolytic drugs recommended for the treatment of AIS usually have a narrow time window. Human urinary kallidinogenase (HUK) was approved by the China Food and Drug Administration (CFDA) in 2005 for the treatment of mild to moderate AIS, and it is thus widely used in China. However, large-scale clinical study data for a more complete understanding of various aspects of its safety and efficacy characteristics are still unavailable. The ongoing Reevaluate the Efficacy and Safety of Human Urinary Kallidinogenase (RESK) trial is designed to reevaluate the safety and efficacy of HUK in Chinese patients with AIS...
March 6, 2017: Translational Stroke Research
https://www.readbyqxmd.com/read/28247188/diabetes-worsens-functional-outcomes-in-young-female-rats-comparison-of-stroke-models-tissue-plasminogen-activator-effects-and-sexes
#12
Weiguo Li, Rebecca Ward, John Paul Valenzuela, Guangkuo Dong, Susan C Fagan, Adviye Ergul
Diabetes worsens stroke outcome and increases the risk of hemorrhagic transformation (HT) after ischemic stroke, especially with tissue plasminogen activator (tPA) treatment. The widespread use of tPA is still limited by the fear of hemorrhagic transformation (HT), and underlying mechanisms are actively being pursued in preclinical studies. However, experimental models use a 10 times higher dose of tPA than the clinical dose (10 mg/kg) and mostly employ only male animals. In this translational study, we hypothesized that low-dose tPA will improve the functional recovery after the embolic stroke in both control and diabetic male and female animals...
March 1, 2017: Translational Stroke Research
https://www.readbyqxmd.com/read/28243834/sodium-tanshinone-iia-sulfonate-enhances-effectiveness-rt-pa-treatment-in-acute-ischemic-stroke-patients-associated-with-ameliorating-blood-brain-barrier-damage
#13
Biying Ji, Fei Zhou, Lijuan Han, Jun Yang, Haijian Fan, Shanshan Li, Jingwei Li, Xin Zhang, Xiaoying Wang, Xiangyan Chen, Yun Xu
Treatment with sodium tanshinone IIA sulfonate (STS) may ameliorate blood-brain barrier (BBB) damage in acute ischemic stroke patients receiving recombinant tissue plasminogen activator (rt-PA) thrombolysis and improve stroke patients' outcome. This randomized, single-center, placebo-controlled clinical trial investigated the potential effects and underlying mechanisms of STS. Forty-two acute ischemic stroke patients receiving intravenous rt-PA thrombolysis were randomized to intravenous administration either with STS (60 mg/day) (n = 21) or with equivalent volume of saline as a placebo (n = 21) after randomization for 10 days...
February 27, 2017: Translational Stroke Research
https://www.readbyqxmd.com/read/27988839/dr%C3%AE-1-mog-35-55-reduces-permanent-ischemic-brain-injury
#14
Jianyi Wang, Qing Ye, Jing Xu, Gil Benedek, Haiyue Zhang, Yuanyuan Yang, Huan Liu, Roberto Meza-Romero, Arthur A Vandenbark, Halina Offner, Yanqin Gao
Stroke induces a catastrophic immune response that involves the global activation of peripheral leukocytes, especially T cells. The human leukocyte antigen-DRα1 domain linked to MOG-35-55 peptide (DRα1-MOG-35-55) is a partial major histocompatibility complex (MHC) class II construct which can inhibit neuroantigen-specific T cells and block binding of the cytokine/chemokine macrophage migration inhibitory factor (MIF) to its CD74 receptor on monocytes and macrophages. Here, we evaluated the therapeutic effect of DRα1-MOG-35-55 in a mouse model of permanent distal middle cerebral artery occlusion (dMCAO)...
June 2017: Translational Stroke Research
https://www.readbyqxmd.com/read/27896625/mri-characterization-in-the-acute-phase-of-experimental-subarachnoid-hemorrhage
#15
Dewei Guo, D Andrew Wilkinson, B Gregory Thompson, Aditya S Pandey, Richard F Keep, Guohua Xi, Ya Hua
A number of mechanisms have been proposed for the early brain injury after subarachnoid hemorrhage (SAH). In this study, we investigated the radiographic characteristics and influence of gender on early brain injury after experimental SAH. SAH was induced by endovascular perforation in male and female rats. Magnetic resonance imaging was performed in a 7.0-T Varian MR scanner at 24 h after SAH. The occurrence and size of T2 lesions, ventricular dilation, and white matter injury (WMI) were determined on T2-weighted images (T2WI)...
June 2017: Translational Stroke Research
https://www.readbyqxmd.com/read/27844273/sex-differences-in-the-cerebral-collateral-circulation
#16
James E Faber, Scott M Moore, Jennifer L Lucitti, Amir Aghajanian, Hua Zhang
Premenopausal women and intact female rodents sustain smaller cerebral infarctions than males. Several sex-dependent differences have been identified as potential contributors, but many questions remain unanswered. Mice exhibit wide variation in native collateral number and diameter (collateral extent) that is dependent on differences in genetic background, aging, and other comorbidities and that contributes to their also-wide differences in infarct volume. Likewise, variation in infarct volume correlates with differences in collateral-dependent blood flow in patients with acute ischemic stroke...
June 2017: Translational Stroke Research
https://www.readbyqxmd.com/read/28251583/stroke-cytoprotection-can-repeating-history-with-new-expectations-really-be-the-path-to-success-in-stroke-research
#17
LETTER
Paul A Lapchak, Victor V Uteshev
No abstract text is available yet for this article.
April 2017: Translational Stroke Research
https://www.readbyqxmd.com/read/28127687/regulated-and-unregulated-clinical-trials-of-stem-cell-therapies-for-stroke
#18
EDITORIAL
Michael G Liska, Marci G Crowley, Cesar V Borlongan
No abstract text is available yet for this article.
April 2017: Translational Stroke Research
https://www.readbyqxmd.com/read/27838820/increased-12-15-lipoxygenase-leads-to-widespread-brain-injury-following-global-cerebral-ischemia
#19
Kazim Yigitkanli, Yi Zheng, Anton Pekcec, Eng H Lo, Klaus van Leyen
Global ischemia following cardiac arrest is characterized by high mortality and significant neurological deficits in long-term survivors. Its mechanisms of neuronal cell death have only partially been elucidated. 12/15-lipoxygenase (12/15-LOX) is a major contributor to delayed neuronal cell death and vascular injury in experimental stroke, but a possible role in brain injury following global ischemia has to date not been investigated. Using a mouse bilateral occlusion model of transient global ischemia which produced surprisingly widespread injury to cortex, striatum, and hippocampus, we show here that 12/15-LOX is increased in a time-dependent manner in the vasculature and neurons of both cortex and hippocampus...
April 2017: Translational Stroke Research
https://www.readbyqxmd.com/read/27837475/pericytes-in-brain-injury-and-repair-after-ischemic-stroke
#20
REVIEW
Wei Cai, Huan Liu, Jingyan Zhao, Lily Y Chen, Jun Chen, Zhengqi Lu, Xiaoming Hu
Pericytes are functional components of the neurovascular unit (NVU). They provide support to other NVU components and maintain normal physiological functions of the blood-brain barrier (BBB). The brain ischemia and reperfusion result in pathological alterations in pericytes. The intimate anatomical and functional interactions between pericytes and other NVU components play pivotal roles in the progression of stroke pathology. In this review, we depict the biology and functions of pericytes in the normal brain and discuss their effects in brain injury and repair after ischemia/reperfusion...
April 2017: Translational Stroke Research
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