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Translational stroke

Le Li, Creed M Stary
Astrocytes and microglia play crucial roles in the response to cerebral ischemia and are effective targets for stroke therapy in animal models. MicroRNAs (miRs) are important posttranscriptional regulators of gene expression that function by inhibiting the translation of select target genes. In astrocytes, miR expression patterns regulate mitochondrial function in response to oxidative stress via targeting of Bcl2 and heat shock protein 70 family members. Mitochondria play an active role in microglial activation, and miRs regulate the microglial neuroinflammatory response...
2016: Oxidative Medicine and Cellular Longevity
Lulu Xie, Hongyi Kang, Maiken Nedergaard
BACKGROUND: Stroke is one of the leading causes of death and disability worldwide. As a consequence, several excellent rodent models have been developed to gain insight into the pathophysiology of stroke and testing the efficacy of neuroprotective interventions. However, one potential problem is that albeit roughly 80% of strokes occur in awake patients, all existing murine stroke models employ anesthesia. Moreover, epidemiological studies have shown that stroke injury is more severe in the minority of patients that suffer stroke while asleep...
2016: Journal of Nature and Science
Amutha Selvamani, Farida Sohrabji
With age, stroke prevalence is higher, and stroke outcome, worse, in women. Thus there is an urgent need to identify stroke neuroprotectants for this population. Using a preclinical stroke model, our studies focused on microRNAs (miRNAs), a class of translational repressors, as neuroprotectants. Analysis of circulating miRNA in the acute phase of stroke indicated potential neuroprotective capacity for miR363. Specifically, mir363 is elevated in serum of adult female rats that typically have small infarct volumes, but is deficient in age-matched males or middle-aged males and females, groups that have greater stroke-associated impairment...
October 20, 2016: Neurochemistry International
Sarah A Moore, Ruth Da Silva, Madelaine Balaam, Lianne Brkic, Dan Jackson, Dan Jamieson, Thomas Ploetz, Helen Rodgers, Lisa Shaw, Frederike van Wijck, Christopher Price
BACKGROUND: Loss of upper limb function affects up to 85 % of acute stroke patients. Recovery of upper limb function requires regular intensive practise of specific upper limb tasks. To enhance intensity of practice interventions are being developed to encourage patients to undertake self-directed exercise practice. Most interventions do not translate well into everyday activities and stroke patients continue to find it difficult remembering integration of upper limb movements into daily activities...
October 21, 2016: Trials
Staci Sue Reynolds, Susan M McLennon, Patricia R Ebright, Laura L Murray, Tamilyn Bakas
RATIONALE: Program evaluation is essential to help determine the success of an evidence-based practice program and assist with translating these processes across settings. AIMS: The purpose of this study was to evaluate the usefulness of 2 competency programs that sought to improve neurocritical care nurses' knowledge of and adherence to evidence-based stroke and spinal cord injury guidelines. These programs consisted of 3 specific implementation strategies, including local opinion leaders, printed educational materials, and educational outreach...
October 20, 2016: Journal of Evaluation in Clinical Practice
Guy Bar-Klein, Rebecca Klee, Claudia Brandt, Marion Bankstahl, Pablo Bascuñana, Kathrin Töllner, Hotjensa Dalipaj, Jens P Bankstahl, Alon Friedman, Wolfgang Löscher
OBJECTIVE: Acquired epilepsy is a devastating long-term risk of various brain insults, including trauma, stroke, infections, and status epilepticus (SE). There is no preventive treatment for patients at risk. Due to the complex alterations involved in epileptogenesis, it is likely that multi-targeted approaches are required for epilepsy prevention. We report novel preclinical findings with isoflurane, which exerts various non-anesthetic effects that may be relevant for anti-epileptogenesis...
October 19, 2016: Annals of Neurology
Su Lui, Xiaohong Joe Zhou, John A Sweeney, Qiyong Gong
Unlike neurologic conditions, such as brain tumors, dementia, and stroke, the neural mechanisms for all psychiatric disorders remain unclear. A large body of research obtained with structural and functional magnetic resonance imaging, positron emission tomography/single photon emission computed tomography, and optical imaging has demonstrated regional and illness-specific brain changes at the onset of psychiatric disorders and in individuals at risk for such disorders. Many studies have shown that psychiatric medications induce specific measurable changes in brain anatomy and function that are related to clinical outcomes...
November 2016: Radiology
Anna Dominiczak
Human primary or essential hypertension is a complex, polygenic trait with some 50% contribution from genes and environment. Richard Lifton and colleagues provided elegant dissection of several rare Mendelian forms of hypertension, exemplified by the glucocorticoid remediable aldosteronism and Liddle's syndrome. These discoveries illustrate that a single gene mutation can explain the entire pathogenesis of severe, early onset hypertension as well as dictating the best treatment.The dissection of the much more common polygenic hypertension has proven much more difficult...
September 2016: Journal of Hypertension
Sreekala S Nampoothiri, Tanvi Potluri, Harshith Subramanian, Rajanikant G Krishnamurthy
Despite years of research, most preclinical trials on ischemic stroke have remained unsuccessful owing to poor methodological and statistical standards leading to "translational roadblocks." Various behavioral tests have been established to evaluate traits such as sensorimotor function, cognitive and social interactions, and anxiety-like and depression-like behavior. A test's validity is of cardinal importance as it influences the chance of a successful translation of preclinical results to clinical settings...
October 17, 2016: Molecular Neurobiology
Julius T Kamwesiga, Lena von Koch, Anders Kottorp, Susanne Guidetti
BACKGROUND: Knowledge is scarce about the impact of stroke in Uganda, and culturally adapted, psychometrically tested patient-reported outcome measures are lacking. The Stroke Impact Scale 3.0 is recommended, but it has not been culturally adapted and validated in Uganda. OBJECTIVE: To culturally adapt and determine the psychometric properties of the Stroke Impact Scale 3.0 in the Ugandan context on a small scale. METHOD: The Stroke Impact Scale 3...
2016: SAGE Open Medicine
Aizpea Aguirrezabal Juaristi, Montse Ferrer Fores, Ester Marco Navarro, Sergi Mojal García, Gemma Vilagut Saiz, Esther Duarte Oller
BACKGROUND AND OBJECTIVE: The Satisfaction Pound Scale is a specific questionnaire to evaluate satisfaction with the rehabilitation program after a stroke. The aim of this study was to adapt this scale to Spanish and to evaluate its metric characteristics. METHOD: The adaptation included translation and back-translation methods. Metric characteristics were evaluated in 74 patients, all of whom were administered the Satisfaction Pound Scale and the Short Form 36 (SF-36)...
October 13, 2016: Medicina Clínica
Georgios Tsivgoulis, Andrei V Alexandrov
PURPOSE OF REVIEW: Low cost, avoidance of irradiation, and high temporal resolution are inherent advantages of ultrasound imaging that translate into multiple clinical uses in many domains of neurology. This article presents clinical uses of ultrasound examination in cerebrovascular, neurodegenerative, and peripheral nervous system diseases. RECENT FINDINGS: Modern treatment and prevention of ischemic stroke rely on prompt diagnosis. Ultrasonography has found a place as a noninvasive screening test and bedside technique that provides estimates of the degree of stenosis as well as hemodynamic and structural information about intracranial and extracranial vessels in real time...
October 2016: Continuum: Lifelong Learning in Neurology
Ruihe Lin, Jingli Cai, Eric W Kostuk, Robert Rosenwasser, Lorraine Iacovitti
BACKGROUND: Dimethyl fumarate (DMF), working via its metabolite monomethylfumarate (MMF), acts as a potent antioxidant and immunomodulator in animal models of neurologic disease and in patients with multiple sclerosis. These properties and their translational potential led us to investigate whether DMF/MMF could also protect at-risk and/or dying neurons in models of ischemic stroke in vitro and in vivo. Although the antioxidant effects have been partially addressed, the benefits of DMF immunomodulation after ischemic stroke still need to be explored...
October 13, 2016: Journal of Neuroinflammation
Jongseong Kim, Jung E Park, Matthias Nahrendorf, Dong-Eog Kim
There is an emergent need for imaging methods to better triage patients with acute stroke for tissue-plasminogen activator (tPA)-mediated thrombolysis or endovascular clot retrieval by directly visualizing the size and distribution of cerebral thromboemboli. Currently, magnetic resonance (MR) or computed tomography (CT) angiography visualizes the obstruction of blood flow within the vessel lumen rather than the thrombus itself. The present visualization method, which relies on observation of the dense artery sign (the appearance of cerebral thrombi on a non-enhanced CT), suffers from low sensitivity...
September 2016: Journal of Stroke
Bert Nitzsche, Elzbieta Dudek, Lukasz Hajdo, Andrzej A Kasprzak, Andrej Vilfan, Stefan Diez
Single-molecule experiments have been used with great success to explore the mechanochemical cycles of processive motor proteins such as kinesin-1, but it has proven difficult to apply these approaches to nonprocessive motors. Therefore, the mechanochemical cycle of kinesin-14 (ncd) is still under debate. Here, we use the readout from the collective activity of multiple motors to derive information about the mechanochemical cycle of individual ncd motors. In gliding motility assays we performed 3D imaging based on fluorescence interference contrast microscopy combined with nanometer tracking to simultaneously study the translation and rotation of microtubules...
October 11, 2016: Proceedings of the National Academy of Sciences of the United States of America
W Brent Keeling, Jose Binongo, Michael E Halkos, Bradley G Leshnower, Duc Q Nguyen, Edward P Chen, Eric L Sarin, Jeffrey S Miller, Steven Macheers, Omar M Lattouf, Robert A Guyton, Vinod H Thourani
BACKGROUND: It has been established that outcomes for black patients undergoing coronary artery bypass graft surgery (CABG) are inferior to those of their white counterparts. The purpose of this study was to determine (1) whether rates of multiarterial grafting are different among black patients and white patients, and (2) whether racial differences exist in postoperative outcomes after accounting for grafting strategy. METHODS: A retrospective review of black patients (n = 2,810) and white patients (n = 13,569) who underwent isolated, primary CABG from January 2002 to June 2014 at a US academic institution was performed...
October 4, 2016: Annals of Thoracic Surgery
Danielle Levac, Stephanie M N Glegg, Heidi Sveistrup, Heather Colquhoun, Patricia A Miller, Hillel Finestone, Vincent DePaul, Jocelyn E Harris, Diana Velikonja
BACKGROUND: Despite increasing evidence for the effectiveness of virtual reality (VR)-based therapy in stroke rehabilitation, few knowledge translation (KT) resources exist to support clinical integration. KT interventions addressing known barriers and facilitators to VR use are required. When environmental barriers to VR integration are less amenable to change, KT interventions can target modifiable barriers related to therapist knowledge and skills. METHODS: A multi-faceted KT intervention was designed and implemented to support physical and occupational therapists in two stroke rehabilitation units in acquiring proficiency with use of the Interactive Exercise Rehabilitation System (IREX; GestureTek)...
October 6, 2016: BMC Health Services Research
Petra Bonova, Miroslava Nemethova, Milina Matiasova, Martin Bona, Miroslav Gottlieb
Ischemic tolerance (IT) has gained attention as an attractive strategy for improving stroke outcome. Recently, it was shown that signal responsible for rapid IT induction (tolerance induction factor- TIF) is transmitted via circulating blood. In the present paper, we have hypothesized about the role of the blood cell compartment in TIF production. We used hind limb ischemia to generate TIF as a rapid preconditioning against transient middle cerebral artery occlusion (MCAO). The essential properties of protein synthesis inhibitors actinomycin D and cycloheximide were utilized to obtain the following results: 1...
October 5, 2016: European Journal of Neuroscience
Mariana Gomez-Smith, Sudhir Karthikeyan, Matthew S Jeffers, Rafal Janik, Lynsie A Thomason, Bojana Stefanovic, Dale Corbett
Many promising findings from pre-clinical research have failed to translate to the clinic due to their inability to incorporate human disease co-morbidity. A variety of rodent diets and feeding durations are currently used in models of human metabolic syndrome, obesity and diabetes. One model, the Cafeteria (CAF) diet, makes use of grocery store-purchased food items that more closely approximate the human ultra-processed diet than commercial high-fat or high-sugar rodent diets. The present study describes the development of metabolic syndrome in rats fed a CAF diet as well as the recovery of metabolic syndrome following a healthy "lifestyle" change...
October 2, 2016: Physiology & Behavior
Mark P Jackson, Asif Rahman, Belen Lafon, Gregory Kronberg, Doris Ling, Lucas C Parra, Marom Bikson
The objective of this review is to summarize the contribution of animal research using direct current stimulation (DCS) to our understanding of the physiological effects of transcranial direct current stimulation (tDCS). We comprehensively address experimental methodology in animal studies, broadly classified as: (1) transcranial stimulation; (2) direct cortical stimulation in vivo and (3) in vitro models. In each case advantages and disadvantages for translational research are discussed including dose translation and the overarching "quasi-uniform" assumption, which underpins translational relevance in all animal models of tDCS...
September 10, 2016: Clinical Neurophysiology: Official Journal of the International Federation of Clinical Neurophysiology
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