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Translational Stroke Research

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https://www.readbyqxmd.com/read/28405804/cytoprotective-drug-tissue-plasminogen-activator-protease-interaction-assays-screening-of-two-novel-cytoprotective-chromones
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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/28236151/can-quality-improvement-tools-overcome-the-translational-roadblock-the-vital-influence-of-the-researcher
#11
EDITORIAL
Serge Marbacher
No abstract text is available yet for this article.
February 24, 2017: Translational Stroke Research
https://www.readbyqxmd.com/read/28205065/spontaneous-recovery-of-upper-extremity-motor-impairment-after-ischemic-stroke-implications-for-stem-cell-based-therapeutic-approaches
#12
Hossein Delavaran, Joseph Aked, Håkan Sjunnesson, Olle Lindvall, Bo Norrving, Zaal Kokaia, Arne Lindgren
Preclinical studies suggest that stem cell therapy (SCT) may improve sensorimotor recovery after stroke. Upper extremity motor impairment (UEMI) is common after stroke, often entailing substantial disability. To evaluate the feasibility of post-stroke UEMI as a target for SCT, we examined a selected sample of stroke patients potentially suitable for SCT, aiming to assess the frequency and recovery of UEMI, as well as its relation to activity limitations and participation restrictions. Patients aged 20-75 years with first-ever ischemic stroke, and National Institutes of Health Stroke Scale (NIHSS) scores 1-18, underwent brain diffusion-weighted MRI within 4 days of stroke onset (n = 108)...
February 15, 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
#13
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
#14
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
#15
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
#16
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
https://www.readbyqxmd.com/read/27807801/role-of-glibenclamide-in-brain-injury-after-intracerebral-hemorrhage
#17
Bing Jiang, Lin Li, Qianwei Chen, Yihao Tao, Liming Yang, Bo Zhang, John H Zhang, Hua Feng, Zhi Chen, Jun Tang, Gang Zhu
Brain edema following intracerebral hemorrhage (ICH) causes severe secondary brain injury, and no efficient pharmacological preventions are available. The present study was designed to demonstrate the neuroprotective effects of glibenclamide on brain edema and key factors of the blood-brain barrier (BBB). The study was divided into two parts. First, we utilized an autoblood-induced rat model to investigate the expression of sulfonylurea receptor 1 (Sur1). Second, rats were randomized into sham, vehicle, and glibenclamide groups...
April 2017: Translational Stroke Research
https://www.readbyqxmd.com/read/27783383/early-erythrolysis-in-the-hematoma-after-experimental-intracerebral-hemorrhage
#18
Ge Dang, Yuefan Yang, Gang Wu, Ya Hua, Richard F Keep, Guohua Xi
Erythrolysis occurs in the clot after intracerebral hemorrhage (ICH), and the release of hemoglobin causes brain injury, but it is unclear when such lysis occurs. The present study examined early erythrolysis in rats. ICH rats had an intracaudate injection of 100 μl autologous blood, and sham rats had a needle insertion. All rats had T2 and T2* magnetic response imaging (MRI) scanning, and brains were used for histology and CD163 (a hemoglobin scavenger receptor) and DARPP-32 (a neuronal marker) immunohistochemistry...
April 2017: Translational Stroke Research
https://www.readbyqxmd.com/read/27623837/higher-cerebrospinal-fluid-ph-may-contribute-to-the-development-of-delayed-cerebral-ischemia-after-aneurysmal-subarachnoid-hemorrhage
#19
Hidenori Suzuki, Masato Shiba, Yoshinari Nakatsuka, Fumi Nakano, Hirofumi Nishikawa
Recent investigations have shown that many factors may cause delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (SAH). To find new potential contributors to DCI, this retrospective study compared gas data in the cerebrospinal fluid (CSF) between patients with and without DCI. The subjects were 61 consecutive patients with SAH classified as Fisher group III on admission computed tomography scans, whose aneurysms were obliterated by clipping or coiling within 24 h post-SAH. Thirty-three patients were treated with CSF drainage...
April 2017: Translational Stroke Research
https://www.readbyqxmd.com/read/27561653/acute-ischemic-stroke-severity-progression-and-outcome-relate-to-changes-in-dipeptidyl-peptidase-iv-and-fibroblast-activation-protein-activity
#20
Lesley Baerts, Raf Brouns, Kaat Kehoe, Robert Verkerk, Sebastiaan Engelborghs, Peter Paul De Deyn, Dirk Hendriks, Ingrid De Meester
Dipeptidyl peptidase IV (DPPIV) inhibition may be a promising therapeutic strategy for acute stroke treatment, given its potential to prolong the biological half-life of neuroprotective substrates. A related protease, fibroblast activation protein (FAP), was recently shown to inactivate the same substrates. Therefore, it should also be investigated as a potential target in stroke. The study aimed to investigate whether stroke severity and outcome correlate with DPPIV and FAP activities and their kinetics shortly after acute ischemic stroke...
April 2017: Translational Stroke Research
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