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Translational Stroke Research

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https://www.readbyqxmd.com/read/28936802/significance-of-mitochondrial-protein-post-translational-modifications-in-pathophysiology-of-brain-injury
#1
Nina Klimova, Aaron Long, Tibor Kristian
Mitochondria are complex organelles that undergo constant fusion and fission in order to adapt to the ever-changing cellular environment. The fusion/fission proteins, localized in the inner and outer mitochondrial membrane, play critical roles under pathological conditions such as acute brain injury and neurodegenerative diseases. Post-translational modifications of these proteins tightly regulate their function and activity, ultimately impacting mitochondrial dynamics and their efficiency to generate ATP. The individual post-translational modifications that are known to affect mitochondrial dynamics include SUMOylation, ubiquitination, phosphorylation, S-nitrosylation, acetylation, O-linked N-acetyl-glucosamine glycosylation, ADP-ribosylation, and proteolytic cleavage...
September 21, 2017: Translational Stroke Research
https://www.readbyqxmd.com/read/28900857/endovascular-biopsy-in-vivo-cerebral-aneurysm-endothelial-cell-sampling-and-gene-expression-analysis
#2
Daniel L Cooke, David B McCoy, Van V Halbach, Steven W Hetts, Matthew R Amans, Christopher F Dowd, Randall T Higashida, Devon Lawson, Jeffrey Nelson, Chih-Yang Wang, Helen Kim, Zena Werb, Charles McCulloch, Tomoki Hashimoto, Hua Su, Zhengda Sun
There is limited data describing endothelial cell (EC) gene expression between aneurysms and arteries partly because of risks associated with surgical tissue collection. Endovascular biopsy (EB) is a lower risk alternative to conventional surgical methods, though no such efforts have been attempted for aneurysms. We sought (1) to establish the feasibility of EB to isolate viable ECs by fluorescence-activated cell sorting (FACS), (2) to characterize the differences in gene expression by anatomic location and rupture status using single-cell qPCR, and (3) to demonstrate the utility of unsupervised clustering algorithms to identify cell subpopulations...
September 13, 2017: Translational Stroke Research
https://www.readbyqxmd.com/read/28875481/proteinuria-predicts-resistance-to-antiplatelet-therapy-in-ischemic-stroke
#3
Gemlyn George, Nikul Patel, Cecilia Jang, David Wheeler, Sridhara S Yaddanapudi, Jonathan Dissin, Ramani Balu, Janani Rangaswami
The occurrence of a stroke while on antiplatelet agents presents a therapeutic dilemma. One of the main causes for recurrent strokes is antiplatelet resistance more commonly known as high on treatment platelet reactivity (HTPR). Prior studies have established that proteinuria is associated with HTPR following myocardial infarction. Here, we investigated whether dipstick proteinuria correlates with HTPR in patients presenting with stroke. We performed a retrospective cohort analysis of 102 patients admitted for a recurrent ischemic stroke that had either a VerifyNow aspirin or VerifyNow clopidogrel laboratory test performed to assess platelet reactivity...
September 5, 2017: Translational Stroke Research
https://www.readbyqxmd.com/read/28849548/precision-medicine-for-ischemic-stroke-let-us-move-beyond-time-is-brain
#4
EDITORIAL
Shao-Hua Yang, Min Lou, Benyan Luo, Wei-Jian Jiang, Ran Liu
No abstract text is available yet for this article.
August 29, 2017: Translational Stroke Research
https://www.readbyqxmd.com/read/28842830/beneficial-effects-of-delayed-p7c3-a20-treatment-after-transient-mcao-in-rats
#5
Zachary B Loris, Justin R Hynton, Andrew A Pieper, W Dalton Dietrich
Despite ischemic stroke being the fifth leading cause of death in the USA, there are few therapeutic options available. We recently showed that the neuroprotective compound P7C3-A20 reduced brain atrophy, increased neurogenesis, and improved functional recovery when treatment was initiated immediately post-reperfusion after a 90-min middle cerebral artery occlusion (MCAO). In the present study, we investigated a more clinically relevant therapeutic window for P7C3-A20 treatment after ischemic stroke. MCAO rats were administered P7C3-A20 for 1 week, beginning immediately or at a delayed point, 6 h post-reperfusion...
August 25, 2017: Translational Stroke Research
https://www.readbyqxmd.com/read/28842824/protein-modifications-with-ubiquitin-as-response-to-cerebral-ischemia-reperfusion-injury
#6
Karin Hochrainer
Post-translational protein modifications present an elegant and energy efficient way to dynamically reprogram cellular protein properties and functions in response to homeostatic imbalance. One such protein modification is the tagging of proteins with the small modifier ubiquitin that can have an impact on protein stability, localization, interaction dynamics, and function. Ubiquitination is vital to any eukaryotic cell under physiological conditions, but even more important under stress including oxidative, genotoxic, and heat stress, where ubiquitination levels are drastically increased...
August 25, 2017: Translational Stroke Research
https://www.readbyqxmd.com/read/28836238/protective-effects-of-autologous-bone-marrow-mononuclear-cells-after-administering-t-pa-in-an-embolic-stroke-model
#7
Bing Yang, Weilang Li, Nikunj Satani, Duyen M Nghiem, XiaoPei Xi, Jaroslaw Aronowski, Sean I Savitz
Tissue plasminogen activator (t-PA) is the only FDA-approved drug for acute ischemic stroke but poses risk for hemorrhagic transformation (HT). Cell therapy has been investigated as a potential therapy to improve recovery after stroke by the modulation of inflammatory responses and the improvement of blood-brain barrier (BBB) integrity, both of which are associated with HT after t-PA. In our present study, we studied the effect of autologous bone marrow mononuclear cells (MNCs) in an embolic stroke model. We administered MNCs in a rat embolic stroke 2 h after administering t-PA...
August 23, 2017: Translational Stroke Research
https://www.readbyqxmd.com/read/28831694/increased-plasma-galectin-3-preceding-the-development-of-delayed-cerebral-infarction-and-eventual-poor-outcome-in-non-severe-aneurysmal-subarachnoid-hemorrhage
#8
Hirofumi Nishikawa, Yoshinari Nakatsuka, Masato Shiba, Fumihiro Kawakita, Masashi Fujimoto, Hidenori Suzuki
A matricellular protein galectin-3 is involved in tissue injury and inflammation, but the role of galectin-3 remains unclear in aneurysmal subarachnoid hemorrhage (SAH). The purpose of this study was to assess whether acute-stage galectin-3 levels were associated with the subsequent development of neurovascular events and outcome after SAH. This study included 83 consecutive patients diagnosed with aneurysmal SAH of resuscitated World Federation of Neurological Surgeons (WFNS) grades 1-3. Plasma galectin-3 levels were once measured on days 1-3 (the day after clipping or coiling)...
August 22, 2017: Translational Stroke Research
https://www.readbyqxmd.com/read/28825223/angiographic-microcirculatory-obstructions-distal-to-occlusion-signify-poor-outcome-after-endovascular-treatment-for-acute-ischemic-stroke
#9
Ethem Murat Arsava, Anil Arat, Mehmet Akif Topcuoglu, Ahmet Peker, Muge Yemisci, Turgay Dalkara
The success of endovascular therapies depends on a number of factors including flow dynamics proximal and distal to the occlusion. The evaluation of antegrade flow distal to the occluded segment is currently a readily available, yet unexplored, option during stentriever-mediated thrombectomy. In this study, we retrospectively evaluated presence of contrast stasis and absence of capillary blush on angiograms obtained by selective injections into the distal site of occlusive thrombi, prior to deployment of stentrievers, in patients undergoing endovascular treatment for acute MCA occlusion...
August 19, 2017: Translational Stroke Research
https://www.readbyqxmd.com/read/28819935/plasma-biomarkers-of-inflammation-reflect-seizures-and-hemorrhagic-activity-of-cerebral-cavernous-malformations
#10
Romuald Girard, Hussein A Zeineddine, Maged D Fam, Anoop Mayampurath, Ying Cao, Changbin Shi, Robert Shenkar, Sean P Polster, Michael Jesselson, Ryan Duggan, Abdul-Ghani Mikati, Gregory Christoforidis, Jorge Andrade, Kevin J Whitehead, Dean Y Li, Issam A Awad
The clinical course of cerebral cavernous malformations (CCMs) is highly variable. Based on recent discoveries implicating angiogenic and inflammatory mechanisms, we hypothesized that serum biomarkers might reflect chronic or acute disease activity. This single-site prospective observational cohort study included 85 CCM patients, in whom 24 a priori chosen plasma biomarkers were quantified and analyzed in relation to established clinical and imaging parameters of disease categorization and severity. We subsequently validated the positive correlations in longitudinal follow-up of 49 subjects...
August 17, 2017: Translational Stroke Research
https://www.readbyqxmd.com/read/28812241/plasma-glycoproteomic-study-of-therapeutic-hypothermia-reveals-novel-markers-predicting-neurologic-outcome-post-cardiac-arrest
#11
Wenjun Deng, Jing Cao, Lei Chen, David McMullin, James L Januzzi, Ferdinando S Buonanno, Eng H Lo, MingMing Ning
Therapeutic hypothermia (TH) is a neuroprotective treatment post-cardiac arrest but is grossly underutilized. After TH induction, traditional biomarkers and parameters can no long predict clinical outcome due to a lack of understanding of hypothermic response. Innovative approaches to better understand the clinical effect of TH will help to prognosticate outcome and expand beneficial population. Protein glycosylation is an important extracellular post-translational modification, regulating various extracellular signaling pathways...
August 15, 2017: Translational Stroke Research
https://www.readbyqxmd.com/read/28770403/route-of-feeding-as-a-proxy-for-dysphagia-after-stroke-and-the-effect-of-transdermal-glyceryl-trinitrate-data-from-the-efficacy-of-nitric-oxide-in-stroke-randomised-controlled-trial
#12
Lisa J Woodhouse, Polly Scutt, Shaheen Hamdy, David G Smithard, David L Cohen, Christine Roffe, Daniel Bereczki, Eivind Berge, Christopher F Bladin, Valeria Caso, Hanne K Christensen, Rónán Collins, Anna Czlonkowska, Asita de Silva, Anwar Etribi, Ann-Charlotte Laska, George Ntaios, Serefnur Ozturk, Stephen J Phillips, Kameshwar Prasad, Szabolcs Szatmari, Nikola Sprigg, Philip M Bath
Post-stroke dysphagia is common, associated with poor outcome and often requires non-oral feeding/fluids. The relationship between route of feeding and outcome, as well as treatment with glyceryl trinitrate (GTN), was studied prospectively. The Efficacy of Nitric Oxide in Stroke (ENOS) trial assessed transdermal GTN (5 mg versus none for 7 days) in 4011 patients with acute stroke and high blood pressure. Feeding route (oral = normal or soft diet; non-oral = nasogastric tube, percutaneous endoscopic gastrostomy tube, parenteral fluids, no fluids) was assessed at baseline and day 7...
August 2, 2017: Translational Stroke Research
https://www.readbyqxmd.com/read/28766251/melatonin-alleviates-intracerebral-hemorrhage-induced-secondary-brain-injury-in-rats-via-suppressing-apoptosis-inflammation-oxidative-stress-dna-damage-and-mitochondria-injury
#13
Zhong Wang, Feng Zhou, Yang Dou, Xiaodi Tian, Chenglin Liu, Haiying Li, Haitao Shen, Gang Chen
Intracerebral hemorrhage (ICH) is a cerebrovascular disease with high mortality and morbidity, and the effective treatment is still lacking. We designed this study to investigate the therapeutic effects and mechanisms of melatonin on the secondary brain injury (SBI) after ICH. An in vivo ICH model was induced via autologous whole blood injection into the right basal ganglia in Sprague-Dawley (SD) rats. Primary rat cortical neurons were treated with oxygen hemoglobin (OxyHb) as an in vitro ICH model. The results of the in vivo study showed that melatonin alleviated severe brain edema and behavior disorders induced by ICH...
August 1, 2017: Translational Stroke Research
https://www.readbyqxmd.com/read/28755277/chronic-remote-ischemic-conditioning-is-cerebroprotective-and-induces-vascular-remodeling-in-a-vcid-model
#14
Mohammad Badruzzaman Khan, Sherif Hafez, Md Nasrul Hoda, Babak Baban, Jesse Wagner, Mohamed E Awad, Hasith Sangabathula, Stephen Haigh, Mohammed Elsalanty, Jennifer L Waller, David C Hess
Vascular contributions to cognitive impairment and dementia (VCID) make up 50% of the cases of dementia. The purpose of this study was to determine the effect of chronic remote ischemic conditioning (C-RIC) on improving long-term (6 months) outcomes and cerebral blood flow (CBF) and collateral formation in a mouse model of VCID. Adult C57BL/6J male mice (10 weeks) were randomly assigned to four different groups: (1) sham-bilateral carotid artery stenosis (BCAS), (2) BCAS + sham RIC, (3) BCAS+C-RIC for 1 month (1MO), and (4) BCAS+C-RIC-4 months (4MO)...
July 28, 2017: Translational Stroke Research
https://www.readbyqxmd.com/read/28752411/alcohol-consumption-and-aneurysmal-subarachnoid-hemorrhage
#15
Anil Can, Victor M Castro, Yildirim H Ozdemir, Sarajune Dagen, Dmitriy Dligach, Sean Finan, Sheng Yu, Vivian Gainer, Nancy A Shadick, Guergana Savova, Shawn Murphy, Tianxi Cai, Scott T Weiss, Rose Du
Alcohol consumption may be a modifiable risk factor for rupture of intracranial aneurysms. Our aim is to evaluate the association between ruptured aneurysms and alcohol consumption, intensity, and cessation. The medical records of 4701 patients with 6411 radiographically confirmed intracranial aneurysms diagnosed at the Brigham and Women's Hospital and Massachusetts General Hospital between 1990 and 2016 were reviewed. Individuals were divided into cases with ruptured aneurysms and controls with unruptured aneurysms...
July 27, 2017: Translational Stroke Research
https://www.readbyqxmd.com/read/28752410/infections-up-to-76%C3%A2-days-after-stroke-increase-disability-and-death
#16
Annastazia E Learoyd, Lisa Woodhouse, Laurence Shaw, Nikola Sprigg, Daniel Bereczki, Eivind Berge, Valeria Caso, Hanne Christensen, Ronan Collins, Anna Czlonkowska, Anwar El Etribi, Tracy D Farr, John Gommans, Ann-Charlotte Laska, George Ntaios, Serefnur Ozturk, Stuart J Pocock, Kameshwar Prasad, Joanna M Wardlaw, Kevin C Fone, Philip M Bath, Rebecca C Trueman
Early infection after stroke is associated with a poor outcome. We aimed to determine whether delayed infections (up to 76 days post-stroke) are associated with poor outcome at 90 days. Data came from the international Efficacy of Nitric Oxide Stroke (ENOS, ISRCTN99414122) trial. Post hoc data on infections were obtained from serious adverse events reports between 1 and 76 days following stroke in this large cohort of patients. Regression models accounting for baseline covariates were used to analyse fatalities and functional outcomes (modified Rankin Scale (mRS), Barthel Index, Euro-Qol-5D) at 90 days, in patients with infection compared to those without infection...
July 27, 2017: Translational Stroke Research
https://www.readbyqxmd.com/read/28744717/novel-regenerative-therapies-based-on-regionally-induced-multipotent-stem-cells-in-post-stroke-brains-their-origin-characterization-and-perspective
#17
REVIEW
Toshinori Takagi, Shinichi Yoshimura, Rika Sakuma, Akiko Nakano-Doi, Tomohiro Matsuyama, Takayuki Nakagomi
Brain injuries such as ischemic stroke cause severe neural loss. Until recently, it was believed that post-ischemic areas mainly contain necrotic tissue and inflammatory cells. However, using a mouse model of cerebral infarction, we demonstrated that stem cells develop within ischemic areas. Ischemia-induced stem cells can function as neural progenitors; thus, we initially named them injury/ischemia-induced neural stem/progenitor cells (iNSPCs). However, because they differentiate into more than neural lineages, we now refer to them as ischemia-induced multipotent stem cells (iSCs)...
July 25, 2017: Translational Stroke Research
https://www.readbyqxmd.com/read/28726167/early-increased-bradykinin-1-receptor-contributes-to-hemorrhagic-transformation-after-ischemic-stroke-in-type-1-diabetic-rats
#18
Hongfei Sang, Zhongming Qiu, Jin Cai, Wenya Lan, Linjie Yu, Hao Zhang, Min Li, Yi Xie, Ruibing Guo, Ruidong Ye, Xinfeng Liu, Ling Liu, Renliang Zhang
Hemorrhagic transformation (HT) is a major complication of ischemic stroke and further deteriorates neurological outcomes. Bradykinin 1 receptor (B1R) has been proven to mediate vasculo-toxicity in various experimental models. However, its role in the development of HT after stroke remains unclear. We detected the B1R expression in brain tissues with or without HT in a rat model of cerebral ischemia/reperfusion (I/R) with type 1 diabetes, showing higher B1R expression in the hemorrhagic areas than the ischemic tissues...
July 19, 2017: Translational Stroke Research
https://www.readbyqxmd.com/read/28718030/precision-stroke-animal-models-the-permanent-mcao-model-should-be-the-primary-model-not-transient-mcao
#19
Devin W McBride, John H Zhang
An argument for preclinical stroke research to make more use of the permanent middle cerebral artery occlusion (MCAO) model, rather than transient MCAO, is presented. Despite STAIR recommending permanent MCAO as the primary model, preclinical stroke research has not been listened. In 2012, Hossmann reported that 64% of the treatment studies for MCAO used prompt transient MCAO models and only 36% of the studies used permanent MCAO or gradual transient MCAO (i.e., embolic stroke model). Then, in 2014 and 2015, 88% of published basic science studies on large vessel occlusion used the transient MCAO model...
July 17, 2017: Translational Stroke Research
https://www.readbyqxmd.com/read/28691141/vinpocetine-inhibits-nf-%C3%AE%C2%BAb-dependent-inflammation-in-acute-ischemic-stroke-patients
#20
Fang Zhang, Chen Yan, Changjuan Wei, Yang Yao, Xiaofeng Ma, Zhongying Gong, Shoufeng Liu, Dawei Zang, Jieli Chen, Fu-Dong Shi, Junwei Hao
Immunity and inflammation play critical roles in the pathogenesis of acute ischemic stroke. Therefore, immune intervention, as a new therapeutic strategy, is worthy of exploration. Here, we tested the inflammation modulator, vinpocetine, for its effect on the outcomes of stroke. For this multi-center study, we recruited 60 patients with anterior cerebral circulation occlusion and onset of stroke that had exceeded 4.5 h but lasted less than 48 h. These patients, after random division into two groups, received either standard management alone (controls) or standard management plus vinpocetine (30 mg per day intravenously for 14 consecutive days, Gedeon Richter Plc...
July 9, 2017: Translational Stroke Research
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