Article
Biochemistry & Molecular Biology
Elodie Hedou, Sara Douceau, Arnaud Chevilley, Alexandre Varangot, Audrey M. Thiebaut, Hortense Triniac, Isabelle Bardou, Carine Ali, Mike Maillasson, Tiziana Crepaldi, Paolo Comoglio, Eloise Lemarchand, Veronique Agin, Benoit D. Roussel, Denis Vivien
Summary: The two-chains form of tPA, tc-tPA, activates the MET receptor in neurons and leads to the recruitment and degradation of NMDARs containing the GluN2B subunit. This process modulates neuronal signaling and survival by controlling the crosstalk between MET and GluN2B subunit of NMDARs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Pharmacology & Pharmacy
Maria D. Valls, Maria Soldado, Jorge Arasa, Miguel Perez-Aso, Adrienne J. Williams, Bruce N. Cronstein, M. Antonia Noguera, M. Carmen Terencio, M. Carmen Montesinos
Summary: Activation of adenosine A(2A) receptor can promote angiogenesis by increasing the expression of annexin A2 in human dermal microvascular endothelial cells, which enhances fibrinolysis and contributes to wound healing and tissue revascularization.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Claire S. Whyte, Hadj Ahmed. Mostefai, Kim M. Baeten, Andrew J. Lucking, David E. Newby, Nuala A. Booth, Nicola J. Mutch
Summary: The resolution of arterial thrombi relies on the endogenous fibrinolytic system. tPA primarily localizes to the thrombus head in a free and active form. Thrombi formed under high shear conditions are more resistant to fibrinolysis due to less tPA and increased PAI-1 concentrations.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Clinical Neurology
Jianhui Jin, Ruirui Wang, Qing Lin
Summary: The study revealed that GluN2B subunits in immature neurons play a significant role in compensatory increases in NMDAR-mediated currents after Ketamine exposure. This indicates that the neonatal brain is particularly vulnerable to the neurotoxic effects of Ketamine.
JOURNAL OF PAIN RESEARCH
(2021)
Review
Biochemistry & Molecular Biology
Manuel Yepes, Yena Woo, Cynthia Martin-Jimenez
Summary: The neurovascular unit is a complex structure involving various cells and components that are essential for maintaining normal neuronal function. Plasminogen activators play a crucial role in regulating the function of the neurovascular unit, with dysfunction leading to neurodegenerative disorders. Research on the expression and function of tissue-type plasminogen activator and urokinase-type plasminogen activator in the neurovascular unit has provided valuable insights into neurovascular and neurodegenerative disorders.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Hematology
Dante Disharoon, Brian G. Trewyn, Paco S. Herson, David W. M. Marr, Keith B. Neeves
Summary: This study developed a platform for co-delivering tPA and plasminogen using microwheels to accelerate clot lysis, surpassing the biochemical speed limit through corkscrew motion. The results demonstrated significant efficacy in lysing plasma clots with this approach.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2022)
Article
Multidisciplinary Sciences
Anna Kufner, Huma Fatima Ali, Martin Ebinger, Jochen B. Fiebach, David S. Liebeskind, Matthias Endres, Bob Siegerink
Summary: The study found that smoking did not provide clear clinical benefit from endovascular therapy incorporating intra-arterial thrombolysis in ischemic stroke patients.
Article
Pharmacology & Pharmacy
Kirstin Meiners, Prisca Hamm, Marcus Gutmann, Jan Niedens, Agnieszka Nowak-Krol, Salvador Pane, Tessa Luehmann
Summary: The study developed three polyethylene glycol (PEG)ylated tPA bioconjugates based on the recombinant human tPA drug Alteplase using site-specific conjugation strategies. These bioconjugates showed improved proteolytic activity, slower inhibition kinetics by PAI-1, and increased hydrodynamic size.
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
(2023)
Article
Obstetrics & Gynecology
Esra Demirel, Reem Sabouni, Neelima Chandra, Ov D. Slayden, David F. Archer
Summary: The study investigates the distribution and concentrations of several receptors and activators within the primate endometrium during artificial menstrual cycles, showing similarities in their expression patterns suggesting overlapping pathways. These findings indicate potential interactions between the plasminogen activator system and steroid receptors in the endometrium.
REPRODUCTIVE SCIENCES
(2022)
Article
Urology & Nephrology
Victor M. Schuettfort, Benjamin Pradere, David D'Andrea, Nico C. Grossmann, Fahad Quhal, Hadi Mostafaei, Ekaterina Laukhtina, Keiichiro Mori, Michael Rink, Pierre I. Karakiewicz, Reza Sari Motlagh, Satoshi Katayama, Yair Lotan, Douglas Scherr, Mohammad Abufaraj, Harun Fajkovica, Eva Comperat, Dmitry Enikeev, Shahrokh F. Shariat
Summary: Elevated preoperative plasma levels of uPA, SuPAR, and PAI-one were confirmed to be associated with aggressive disease features and worse survival outcomes in patients treated with RC for UCB. These biomarkers have the potential to identify patients who may benefit from intensified/multimodal therapy and improve the discriminatory power of predictive/prognostic models.
JOURNAL OF UROLOGY
(2021)
Review
Medicine, General & Internal
Melinda B. Roaldsen, Haakon Lindekleiv, Ellisiv B. Mathiesen
Summary: In patients with acute wake-up ischemic stroke, both intravenous thrombolytic treatment and endovascular thrombectomy of large vessel occlusion improve functional outcome without increasing the risk of death. However, a possible increased risk of symptomatic intracranial hemorrhage associated with thrombolytic treatment cannot be ruled out. Further studies are needed to determine the optimal criteria for selecting patients for treatment.
COCHRANE DATABASE OF SYSTEMATIC REVIEWS
(2021)
Article
Multidisciplinary Sciences
Eyal Rozenfeld, Merav Tauber, Yair Ben-Chaim, Moshe Parnas
Summary: This study demonstrates that muscarinic receptors are regulated by membrane potential in vivo, impacting behavior, indicating the significant role of GPCR voltage dependence in neuronal coding and behavioral output.
NATURE COMMUNICATIONS
(2021)
Article
Biology
Matthieu Lepine, Sara Douceau, Gabrielle Devienne, Paul Prunotto, Sophie Lenoir, Caroline Regnauld, Elsa Pouettre, Juliette Piquet, Laurent Lebouvier, Yannick Hommet, Eric Maubert, Veronique Agin, Bertrand Lambolez, Bruno Cauli, Carine Ali, Denis Vivien
Summary: The study reveals that tPA released from cortical FS-PV interneurons in the central nervous system can reduce the density of PNNs by degrading CSPGs. This finding provides valuable insights into the control of brain plasticity.
Article
Health Care Sciences & Services
Hee Young Cho, Han Sung Park, Eun Hee Ahn, Eun Ju Ko, Hyeon Woo Park, Young Ran Kim, Ji Hyang Kim, Woo Sik Lee, Nam Keun Kim
Summary: The study revealed that PAI-1 rs1050955 and REN 10795 rs5707 alleles may decrease the risk of RPL, while the tPA rs4646972 genotype may increase the risk of RPL.
JOURNAL OF PERSONALIZED MEDICINE
(2021)
Review
Cell Biology
Steven L. Gonias
Summary: Tissue-type plasminogen activator (tPA) and urokinase-type plasminogen activator (uPA) are serine proteases that play a crucial role in fibrinolysis in mammalian systems. Cells have evolved receptor systems to detect and respond to tPA and uPA, impacting various aspects of cell physiology. This review highlights the structure and function of plasminogen activator receptor assemblies and their role in regulating innate immunity and inflammation.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2021)
Article
Clinical Neurology
Thomas Metayer, Cyrille Orset, Carine Ali, Jonathane Furon, Nicolas Szabla, Evelyne Emery, Denis Vivien, Thomas Gaberel
Summary: The development of hydrocephalus post-SAH may be related to excessive CSF secretion by the choroid plexus, which can be limited by ICV injection of bumetanide. However, other mechanisms may also be involved in post-SAH acute hydrocephalus.
ACTA NEUROCHIRURGICA
(2022)
Article
Engineering, Biomedical
Arthur Chavignon, Baptiste Heiles, Vincent Hingot, Cyrille Orset, Denis Vivien, Olivier Couture
Summary: This article presents the implementation of volumetric ultrasound imaging for micro-angiography in the rat brain. The study demonstrates the ability to achieve unprecedented resolution with a simple and light setup, providing potential applications in both preclinical and clinical studies.
IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING
(2022)
Article
Clinical Neurology
Estelle R. Louet, Martina Glavan, Cyrille Orset, Jerome Parcq, Daniel F. Hanley, Denis Vivien
Summary: This study reveals the importance of tPA-dependent endothelial NMDAR signaling in the formation and rupture of intracranial aneurysms (IAs). By using a monoclonal antibody, Glunomab (R), to block this process, the rate of IA formation and rupture can be reduced, suggesting its potential as a therapeutic candidate for this devastating disease.
TRANSLATIONAL STROKE RESEARCH
(2022)
Article
Hematology
Marc V. A. van Moorsel, Steven de Maat, Kristof Vercruysse, Esther M. van Leeuwen, Charlene Jacqmarcq, Thomas Bonnard, Denis Vivien, H. Bart van der Worp, Rick M. Dijkhuizen, Coen Maas
Summary: Recombinant human tissue plasminogen activator (rh-tPA) and Microlyse are both important thrombolytic agents for the treatment of acute ischemic stroke, but they have different mechanisms. rh-tPA activates plasminogen by binding to fibrin, while Microlyse activates plasminogen by binding to von Willebrand factor (VWF). The study results show that both thrombolytic agents can increase cortical reperfusion and reduce cerebral lesion volume in different types of thrombus models. However, only Microlyse can reduce cerebral lesion volume in the platelet-rich model.
Article
Endocrinology & Metabolism
Antoine Drieu, Anastasia Lanquetin, Paul Prunotto, Zuhal Gulhan, Swannie Pedron, Gloria Vegliante, Daniele Tolomeo, Sophie Serriere, Johnny Vercouillie, Laurent Galineau, Clovis Tauber, Bertrand Kuhnast, Marina Rubio, Elisa R. Zanier, Damien Levard, Sylvie Chalon, Denis Vivien, Carine Ali
Summary: This study investigates the relationship between cognitive dysfunction and neuro-inflammation caused by mild traumatic brain injury (TBI) using animal models and imaging techniques. The results show that even without evidence of brain contusion or bleeding, mild TBI can lead to persistent behavioral deficits and can be detected by PET imaging.
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
(2022)
Article
Medicine, Research & Experimental
Hyeongju Kim, Sophie Lenoir, Angela Helfricht, Taeyang Jung, Zhana K. Karneva, Yejin Lee, Wouter Beumer, Geert B. van der Horst, Herma Anthonijsz, Levi C. M. Buil, Frits van der Ham, Gerard J. Platenburg, Pasi Purhonen, Hans Hebert, Sandrine Humbert, Frederic Saudou, Pontus Klein, Ji-Joon Song
Summary: This study demonstrates the therapeutic potential of targeting HTT exon 12 in Huntington's disease. Truncation of HTT exon 12 does not affect the main physiological functions of HTT, and pharmacological induction of HTT & UDelta;12 reduces HTT aggregation and increases dendritic spine count.
Article
Biology
Matthieu Lepine, Sara Douceau, Gabrielle Devienne, Paul Prunotto, Sophie Lenoir, Caroline Regnauld, Elsa Pouettre, Juliette Piquet, Laurent Lebouvier, Yannick Hommet, Eric Maubert, Veronique Agin, Bertrand Lambolez, Bruno Cauli, Carine Ali, Denis Vivien
Summary: The study reveals that tPA released from cortical FS-PV interneurons in the central nervous system can reduce the density of PNNs by degrading CSPGs. This finding provides valuable insights into the control of brain plasticity.
Article
Biochemistry & Molecular Biology
Edelweiss Touron, Ines Moulinet, Elizabeth Kuhn, Siya Sherif, Valentin Ourry, Brigitte Landeau, Florence Mezenge, Denis Vivien, Olga M. Klimecki, Geraldine Poisnel, Natalie L. Marchant, Gael Chetelat
Summary: Subclinical depressive symptoms are associated with increased risk of Alzheimer's disease, and this study found that these symptoms are linked to neurodegenerative changes in the brain.
MOLECULAR PSYCHIATRY
(2022)
Article
Neurosciences
Vincent Zuba, Jonathane Furon, Mathys Bellemain-Sagnard, Sara Martinez de Lazarrondo, Laurent Lebouvier, Marina Rubio, Yannick Hommet, Maxime Gauberti, Denis Vivien, Carine Ali
Summary: This study found that vascular tPA can reach the brain parenchyma through choroid plexus epithelial cells, providing new insights for the treatment of CNS disorders.
FLUIDS AND BARRIERS OF THE CNS
(2022)
Article
Clinical Neurology
Alin Borha, Florent Lebrun, Emmanuel Touze, Evelyne Emery, Denis Vivien, Thomas Gaberel
Summary: Endovascular thrombectomy has changed the management of ischemic stroke. Decompressive craniectomy for ischemic stroke after thrombectomy could lead to a higher risk of hemorrhagic transformation, as shown in a mouse model of stroke induced by occlusion of the middle cerebral artery.
Article
Cell Biology
Alexandre Varangot, Simon Lebatard, Mathys Bellemain-Sagnard, Laurent Lebouvier, Yannick Hommet, Denis Vivien
Summary: The neuronal expression of tPA has important implications in the physiopathology of the central nervous system. The mechanisms regulating the neuronal trafficking of tPA are unknown.
CELL DEATH & DISEASE
(2023)
Article
Neurosciences
Jonathane Furon, Merve Yetim, Elsa Pouettre, Sara Martinez de Lizarrondo, Eric Maubert, Yannick Hommet, Laurent Lebouvier, Ze Zheng, Carine Ali, Denis Vivien
Summary: This study reveals a new mechanism of regulation of neurovascular coupling (NVC) by demonstrating the role of tPA and NMDARs.
FLUIDS AND BARRIERS OF THE CNS
(2023)
Article
Medicine, General & Internal
Melanie Roussel, Ben Bloom, Mehdi Taalba, Christophe Choquet, Delphine Douillet, Florent Femy, Alexis Marouk, Judith Gorlicki, Camille Gerlier, Richard Macrez, Emilien Arnaud, Rudy Bompard, Emmanuel Montassier, Olivier Hugli, Charlotte Czopik, Xavier Eyer, Axel Benhamed, Olivier Peyrony, Tahar Chouihed, Andrea Penaloza, Alessio Marra, Said Laribi, Paul-Georges Reuter, Wilhelm Behringer, Marion Douplat, Jeremy Guenezan, Nicolas Javaud, Olivier Lucidarme, Marine Cachanado, Ainhoa Aparicio-Monforte, Yonathan Freund
Summary: Despite the validation of clinical decision rules, there has been an increase in the use of CTPA for suspected pulmonary embolism in the emergency department, along with a higher number of diagnosed PEs and especially low-risk PEs.
ANNALS OF INTERNAL MEDICINE
(2023)
Article
Clinical Neurology
Elizabeth Kuhn, Audrey Perrotin, Renaud La Joie, Edelweiss Touron, Sophie Dautricourt, Matthieu Vanhoutte, Denis Vivien, Vincent de La Sayette, Gael Chetelat
Summary: This study aimed to assess the association between informant-reported subjective memory decline and Alzheimer disease biomarkers. The results showed a strong correlation between the informant report and higher amyloid deposition as well as lower cognitive performance in patients with mild cognitive impairment.
Article
Engineering, Electrical & Electronic
Herman Verinaz-Jadan, Carmel L. Howe, Pingfan Song, Flavie Lesept, Josef Kittler, Amanda J. Foust, Pier Luigi Dragotti
Summary: Light Field Microscopy (LFM) is an imaging technique that enables fast dynamics study in biological systems. This work introduces a deep neural network for LFM to image neuronal activity in adverse conditions. The network architecture is based on the sparse nature of neurons and employs a linear convolutional neural network to fit the physics of the acquisition process. With a semi-supervised training framework and physics knowledge, the proposed method outperforms typical deep learning and model-based reconstruction strategies for imaging neuronal activity in mammalian brain tissue via LFM.
IEEE TRANSACTIONS ON COMPUTATIONAL IMAGING
(2023)