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Denis Vivien

Alejandra Daruich, Jérôme Parcq, Kimberley Delaunay, Marie-Christine Naud, Quentin Le Rouzic, Emilie Picard, Patricia Crisanti, Denis Vivien, Marianne Berdugo, Francine Behar-Cohen
PURPOSE: Intravitreal recombinant tissue plasminogen activator (rtPA) is used off-label for the surgical management of submacular hemorrhage, a severe complication of neovascular age-related macular degeneration. rtPA is approved for coronary and cerebral thrombolysis. However, in ischemic stroke rtPA is known to increase excitotoxic neural cell death by interacting with the N-methyl-D-aspartate (NMDA) receptor. We therefore investigated the retinal toxicity of rtPA in healthy rats and in a model of NMDA-induced retinal excitotoxicity...
2016: Molecular Vision
Flavie Lesept, Arnaud Chevilley, Julie Jezequel, Laurent Ladépêche, Richard Macrez, Margaux Aimable, Sophie Lenoir, Thomas Bertrand, Laëtitia Rubrecht, Pascale Galea, Laurent Lebouvier, Karl-Uwe Petersen, Yannick Hommet, Eric Maubert, Carine Ali, Laurent Groc, Denis Vivien
N-methyl-d-aspartate receptors (NMDARs) are ion channels whose synaptic versus extrasynaptic localization critically influences their functions. This distribution of NMDARs is highly dependent on their lateral diffusion at the cell membrane. Each obligatory subunit of NMDARs (GluN1 and GluN2) contains two extracellular clamshell-like domains with an agonist-binding domain and a distal N-terminal domain (NTD). To date, the roles and dynamics of the NTD of the GluN1 subunit in NMDAR allosteric signaling remain poorly understood...
November 10, 2016: Cell Death & Disease
Didier Leys, Yannick Hommet, Clémence Jacquet, Solène Moulin, Igor Sibon, Jean-Louis Mas, Thierry Moulin, Maurice Giroud, Sharmila Sagnier, Charlotte Cordonnier, Elisabeth Medeiros de Bustos, Guillaume Turc, Thomas Ronzière, Yannick Bejot, Olivier Detante, Thavarak Ouk, Anne-Marie Mendyk, Pascal Favrole, Mathieu Zuber, Aude Triquenot-Bagan, Ozlem Ozkul-Wermester, Francisco Macian Montoro, Chantal Lamy, Anthony Faivre, Laurent Lebouvier, Camille Potey, Mathilde Poli, Hilde Hénon, Pauline Renou, Nelly Dequatre-Ponchelle, Marie Bodenant, Sabrina Debruxelles, Costanza Rossi, Régis Bordet, Denis Vivien
OBJECTIVE: To determine whether the ratio single chain (sc)/(sc + 2 chain [tc]) recombinant tissue plasminogen activator (rtPA) influences outcomes in patients with cerebral ischemia. METHODS: We prospectively included consecutive patients treated with IV rtPA for cerebral ischemia in 13 stroke centers and determined the sc/(sc + tc) ratio in the treatment administered to each patient. We evaluated the outcome with the modified Rankin Scale (mRS) at 3 months (prespecified analysis) and occurrence of epileptic seizures (post hoc analysis)...
November 4, 2016: Neurology
Sara Martinez de Lizarrondo, Maxime Gauberti, Denis Vivien
Tuning the endogenous fibrinolytic system to prevent excessive thrombus formation is a tempting prophylactic strategy for thrombosis-related disorders [1]. However, we currently lack approved treatments able to induce a sustained hyperfibrinolytic state in humans. In this regard, valproic acid (VPA), a widely used antiepileptic drug, may be of clinical interest. Besides its still not fully understood antiepileptic properties, VPA is a class I selective histodeacetylase (HDAC) inhibitor and thus affects epigenetic regulation of gene expression [2]...
October 6, 2016: Journal of Thrombosis and Haemostasis: JTH
Marie Hébert, Antoine Anfray, Arnaud Chevilley, Sara Martinez de Lizarrondo, Aurélien Quenault, Morgane Louessard, Benoit D Roussel, Pauline Obiang, Etienne Save, Cyrille Orset, Eric Maubert, Denis Vivien, Véronique Agin
In humans, spatial cognition and navigation impairments are a frequent situation during physiological and pathological aging, leading to a dramatic deterioration in the quality of life. Despite the discovery of neurons with location-specific activity in rodents, that is, place cells in the hippocampus and later on grid cells in the entorhinal cortex (EC), the molecular mechanisms underlying spatial cognition are still poorly known. Our present data bring together in an unusual combination 2 molecules of primary biological importance: a major neuronal excitatory receptor, N-methyl-D-aspartate receptor (NMDAR), and an extracellular protease, tissue plasminogen activator (tPA), in the control of spatial navigation...
September 9, 2016: Cerebral Cortex
Paul Bowie, Elaine McNaughton, David Bruce, Deirdre Holly, Eleanor Forrest, Marion Macleod, Susan Kennedy, Ailsa Power, Denis Toppin, Irene Black, Janet Pooley, Audrey Taylor, Vivien Swanson, Moya Kelly, Julie Ferguson, Suzanne Stirling, Judy Wakeling, Angela Inglis, John McKay, Joan Sargeant
INTRODUCTION: Significant event analysis (SEA) is well established in many primary care settings but can be poorly implemented. Reasons include the emotional impact on clinicians and limited knowledge of systems thinking in establishing why events happen and formulating improvements. To enhance SEA effectiveness, we developed and tested "guiding tools" based on human factors principles. METHODS: Mixed-methods development of guiding tools (Personal Booklet-to help with emotional demands and apply a human factors analysis at the individual level; Desk Pad-to guide a team-based systems analysis; and a written Report Format) by a multiprofessional "expert" group and testing with Scottish primary care practitioners who submitted completed enhanced SEA reports...
2016: Journal of Continuing Education in the Health Professions
Richard Macrez, Peter K Stys, Denis Vivien, Stuart A Lipton, Fabian Docagne
Research advances support the idea that excessive activation of the glutamatergic pathway plays an important part in the pathophysiology of multiple sclerosis. Beyond the well established direct toxic effects on neurons, additional sites of glutamate-induced cell damage have been described, including effects in oligodendrocytes, astrocytes, endothelial cells, and immune cells. Such toxic effects could provide a link between various pathological aspects of multiple sclerosis, such as axonal damage, oligodendrocyte cell death, demyelination, autoimmunity, and blood-brain barrier dysfunction...
September 2016: Lancet Neurology
Matthieu Legrand, Maud Gits-Muselli, Louis Boutin, Dea Garcia-Hermoso, Véronique Maurel, Sabri Soussi, Mourad Benyamina, Axelle Ferry, Maïté Chaussard, Samia Hamane, Blandine Denis, Sophie Touratier, Nicolas Guigue, Emilie Fréalle, Mathieu Jeanne, Jean-Vivien Shaal, Charles Soler, Maurice Mimoun, Marc Chaouat, Matthieu Lafaurie, Alexandre Mebazaa, Stéphane Bretagne, Alexandre Alanio
BACKGROUND:  Invasive wound mucormycosis (IWM) is associated with an extremely poor outcome among critically ill burn patients. The purpose of this study was to describe the detection of circulating Mucorales DNA for the early recognition of IWM in critically ill burn patients and to report the potential value of detecting circulating Mucorales DNA (cmDNA) for treatment guidance. METHODS:  Severely ill burn patients admitted to a tertiary referral center between October 2013 and February 2016 were included...
August 17, 2016: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
Oscar A Marcos-Contreras, Sara Martinez de Lizarrondo, Isabelle Bardou, Cyrille Orset, Mathilde Pruvost, Antoine Anfray, Yvann Frigout, Yannick Hommet, Laurent Lebouvier, Joan Montaner, Denis Vivien, Maxime Gauberti
Hyperfibrinolysis is a systemic condition occurring in various clinical disorders such as trauma, liver cirrhosis or leukemia. Apart from increased bleeding tendency, the pathophysiological consequences of hyperfibrinolysis remain largely unknown. Our present aim was to develop an experimental model of hyperfibrinolysis and to study its effects on the homeostasis of the blood brain barrier (BBB). We induced a sustained hyperfibrinolytic state in mice by hydrodynamic transfection of a plasmid encoding for tissue-type plasminogen activator (tPA)...
August 16, 2016: Blood
Richard Macrez, Maria C Ortega, Isabelle Bardou, Anupriya Mehra, Antoine Fournier, Susanne M A Van der Pol, Benoit Haelewyn, Eric Maubert, Flavie Lesept, Arnaud Chevilley, Fernando de Castro, Helga E De Vries, Denis Vivien, Diego Clemente, Fabian Docagne
Multiple sclerosis is among the most common causes of neurological disability in young adults. Here we provide the preclinical proof of concept of the benefit of a novel strategy of treatment for multiple sclerosis targeting neuroendothelial N-methyl-D-aspartate glutamate receptors. We designed a monoclonal antibody against N-methyl-D-aspartate receptors, which targets a regulatory site of the GluN1 subunit of N-methyl-D-aspartate receptor sensitive to the protease tissue plasminogen activator. This antibody reverted the effect of tissue plasminogen activator on N-methyl-D-aspartate receptor function without affecting basal N-methyl-D-aspartate receptor activity (n = 21, P < 0...
September 2016: Brain: a Journal of Neurology
(no author information available yet)
No abstract text is available yet for this article.
June 2016: Annals of Intensive Care
Cyrille Orset, Benoit Haelewyn, Stuart M Allan, Saema Ansar, Francesco Campos, Tae Hee Cho, Anne Durand, Mohamad El Amki, Marc Fatar, Isaac Garcia-Yébenes, Maxime Gauberti, Saskia Grudzenski, Ignacio Lizasoain, Eng Lo, Richard Macrez, Isabelle Margaill, Samaneh Maysami, Stephen Meairs, Norbert Nighoghossian, Josune Orbe, Jose Antonio Paramo, Jean-Jacques Parienti, Nancy J Rothwell, Marina Rubio, Christian Waeber, Alan R Young, Emmanuel Touzé, Denis Vivien
BACKGROUND AND PURPOSE: The debate over the fact that experimental drugs proposed for the treatment of stroke fail in the translation to the clinical situation has attracted considerable attention in the literature. In this context, we present a retrospective pooled analysis of a large data set from preclinical studies, to examine the effects of early versus late administration of intravenous recombinant tissue-type plasminogen activator. METHODS: We collected data from 26 individual studies from 9 international centers (13 researchers; 716 animals) that compared recombinant tissue-type plasminogen activator with controls, in a unique mouse model of thromboembolic stroke induced by an in situ injection of thrombin into the middle cerebral artery...
May 2016: Stroke; a Journal of Cerebral Circulation
Aurélien Briens, Maxime Gauberti, Jérôme Parcq, Joan Montaner, Denis Vivien, Sara Martinez de Lizarrondo
Cell-derived microparticles (MPs) are nano-sized vesicles released by activated cells in the extracellular milieu. They act as vectors of biological activity by carrying membrane-anchored and cytoplasmic constituents of the parental cells. Although detection and characterization of cell-derived MPs may be of high diagnostic and prognostic values in a number of human diseases, reliable measurement of their size, number and biological activity still remains challenging using currently available methods. In the present study, we developed a protocol to directly image and functionally characterize MPs using high-resolution laser-scanning confocal microscopy...
2016: Theranostics
Anthony Garnier, Mohamad Hamieh, Aurélie Drouet, Jérôme Leprince, Denis Vivien, Thierry Frébourg, Brigitte Le Mauff, Jean-Baptiste Latouche, Olivier Toutirais
Owing to their multiple immune functions, CD4(+) T cells are of major interest for immunotherapy in chronic viral infections and cancer, as well as for severe autoimmune diseases and transplantation. Therefore, standardized methods allowing rapid generation of a large number of CD4(+) T cells for adoptive immunotherapy are still awaited. We constructed stable artificial antigen-presenting cells (AAPCs) derived from mouse fibroblasts. They were genetically modified to express human leukocyte antigen (HLA)-DR molecules and the human accessory molecules B7...
August 2016: Immunology and Cell Biology
Samaneh Maysami, Raymond Wong, Jesus M Pradillo, Adam Denes, Hiramani Dhungana, Tarja Malm, Jari Koistinaho, Cyrille Orset, Mahbubur Rahman, Marina Rubio, Markus Schwaninger, Denis Vivien, Philip M Bath, Nancy J Rothwell, Stuart M Allan
Stroke represents a global challenge and is a leading cause of permanent disability worldwide. Despite much effort, translation of research findings to clinical benefit has not yet been successful. Failure of neuroprotection trials is considered, in part, due to the low quality of preclinical studies, low level of reproducibility across different laboratories and that stroke co-morbidities have not been fully considered in experimental models. More rigorous testing of new drug candidates in different experimental models of stroke and initiation of preclinical cross-laboratory studies have been suggested as ways to improve translation...
March 2016: Journal of Cerebral Blood Flow and Metabolism
Arnaud Chevilley, Flavie Lesept, Sophie Lenoir, Carine Ali, Jérôme Parcq, Denis Vivien
Tissue-type plasminogen activator (tPA) a serine protease is constituted of five functional domains through which it interacts with different substrates, binding proteins, and receptors. In the last years, great interest has been given to the clinical relevance of targeting tPA in different diseases of the central nervous system, in particular stroke. Among its reported functions in the central nervous system, tPA displays both neurotrophic and neurotoxic effects. How can the protease mediate such opposite functions remain unclear but several hypotheses have been proposed...
2015: Frontiers in Cellular Neuroscience
Anupriya Mehra, Carine Ali, Jérôme Parcq, Denis Vivien, Fabian Docagne
The plasminogen activation (PA) system consists in a group of proteases and protease inhibitors regulating the activation of the zymogen plasminogen into its proteolytically active form, plasmin. Here, we give an update of the current knowledge about the role of the PA system on different aspects of neuroinflammation. These include modification in blood-brain barrier integrity, leukocyte diapedesis, removal of fibrin deposits in nervous tissues, microglial activation and neutrophil functions. Furthermore, we focus on the molecular mechanisms (some of them independent of plasmin generation and even of proteolysis) and target receptors responsible for these effects...
March 2016: Biochimica et Biophysica Acta
Julie Belliere, Sara Martinez de Lizarrondo, Robin P Choudhury, Aurélien Quenault, Audrey Le Béhot, Christine Delage, Dominique Chauveau, Joost P Schanstra, Jean-Loup Bascands, Denis Vivien, Maxime Gauberti
Endothelial activation is a hallmark of cardiovascular diseases, acting either as a cause or a consequence of organ injury. To date, we lack suitable methods to measure endothelial activation in vivo. In the present study, we developed a magnetic resonance imaging (MRI) method allowing non-invasive endothelial activation mapping in the vasculature of the main organs affected during cardiovascular diseases. In clinically relevant contexts in mice (including systemic inflammation, acute and chronic kidney diseases, diabetes mellitus and normal aging), we provided evidence that this method allows detecting endothelial activation before any clinical manifestation of organ failure in the brain, kidney and heart with an exceptional sensitivity...
2015: Theranostics
Morgane Louessard, Alexandre Lacroix, Magalie Martineau, Gregoire Mondielli, Axel Montagne, Flavie Lesept, Bertrand Lambolez, Bruno Cauli, Jean-Pierre Mothet, Denis Vivien, Eric Maubert
Although the extracellular serine protease tissue plasminogen activator (tPA) is involved in pathophysiological processes such as learning and memory, anxiety, epilepsy, stroke, and Alzheimer's disease, information about its regional, cellular, and subcellular distribution in vivo is lacking. In the present study, we observed, in healthy mice and rats, the presence of tPA in endothelial cells, oligodendrocytes, mastocytes, and ependymocytes, but not in pericytes, microglial cells, and astrocytes. Moreover, blockage of the axo-dendritic transport unmasked tPA expression in neurons of cortical and hippocampal areas...
September 2016: Molecular Neurobiology
Gemma Llovera, Kerstin Hofmann, Stefan Roth, Angelica Salas-Pérdomo, Maura Ferrer-Ferrer, Carlo Perego, Elisa R Zanier, Uta Mamrak, Andre Rex, Hélène Party, Véronique Agin, Claudine Fauchon, Cyrille Orset, Benoît Haelewyn, Maria-Grazia De Simoni, Ulrich Dirnagl, Ulrike Grittner, Anna M Planas, Nikolaus Plesnila, Denis Vivien, Arthur Liesz
Numerous treatments have been reported to provide a beneficial outcome in experimental animal stroke models; however, these treatments (with the exception of tissue plasminogen activator) have failed in clinical trials. To improve the translation of treatment efficacy from bench to bedside, we have performed a preclinical randomized controlled multicenter trial (pRCT) to test a potential stroke therapy under circumstances closer to the design and rigor of a clinical randomized control trial. Anti-CD49d antibodies, which inhibit the migration of leukocytes into the brain, were previously investigated in experimental stroke models by individual laboratories...
August 5, 2015: Science Translational Medicine
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