Search

Your search keyword '"Denes, Adam"' showing total 191 results
Start Over Author "Denes, Adam"
191 results on '"Denes, Adam"'

3. Microglia states and nomenclature: A field at its crossroads

Author

Paolicelli, Rosa C, Sierra, Amanda, Stevens, Beth, Tremblay, Marie-Eve, Aguzzi, Adriano, Ajami, Bahareh, Amit, Ido, Audinat, Etienne, Bechmann, Ingo, Bennett, Mariko, Bennett, Frederick, Bessis, Alain, Biber, Knut, Bilbo, Staci, Blurton-Jones, Mathew, Boddeke, Erik, Brites, Dora, Brône, Bert, Brown, Guy C, Butovsky, Oleg, Carson, Monica J, Castellano, Bernardo, Colonna, Marco, Cowley, Sally A, Cunningham, Colm, Davalos, Dimitrios, De Jager, Philip L, de Strooper, Bart, Denes, Adam, Eggen, Bart JL, Eyo, Ukpong, Galea, Elena, Garel, Sonia, Ginhoux, Florent, Glass, Christopher K, Gokce, Ozgun, Gomez-Nicola, Diego, González, Berta, Gordon, Siamon, Graeber, Manuel B, Greenhalgh, Andrew D, Gressens, Pierre, Greter, Melanie, Gutmann, David H, Haass, Christian, Heneka, Michael T, Heppner, Frank L, Hong, Soyon, Hume, David A, Jung, Steffen, Kettenmann, Helmut, Kipnis, Jonathan, Koyama, Ryuta, Lemke, Greg, Lynch, Marina, Majewska, Ania, Malcangio, Marzia, Malm, Tarja, Mancuso, Renzo, Masuda, Takahiro, Matteoli, Michela, McColl, Barry W, Miron, Veronique E, Molofsky, Anna Victoria, Monje, Michelle, Mracsko, Eva, Nadjar, Agnes, Neher, Jonas J, Neniskyte, Urte, Neumann, Harald, Noda, Mami, Peng, Bo, Peri, Francesca, Perry, V Hugh, Popovich, Phillip G, Pridans, Clare, Priller, Josef, Prinz, Marco, Ragozzino, Davide, Ransohoff, Richard M, Salter, Michael W, Schaefer, Anne, Schafer, Dorothy P, Schwartz, Michal, Simons, Mikael, Smith, Cody J, Streit, Wolfgang J, Tay, Tuan Leng, Tsai, Li-Huei, Verkhratsky, Alexei, von Bernhardi, Rommy, Wake, Hiroaki, Wittamer, Valérie, Wolf, Susanne A, Wu, Long-Jun, and Wyss-Coray, Tony

Subjects
Microglia, Neurosciences, Psychology, Cognitive Sciences, Neurology & Neurosurgery
Abstract

Microglial research has advanced considerably in recent decades yet has been constrained by a rolling series of dichotomies such as "resting versus activated" and "M1 versus M2." This dualistic classification of good or bad microglia is inconsistent with the wide repertoire of microglial states and functions in development, plasticity, aging, and diseases that were elucidated in recent years. New designations continuously arising in an attempt to describe the different microglial states, notably defined using transcriptomics and proteomics, may easily lead to a misleading, although unintentional, coupling of categories and functions. To address these issues, we assembled a group of multidisciplinary experts to discuss our current understanding of microglial states as a dynamic concept and the importance of addressing microglial function. Here, we provide a conceptual framework and recommendations on the use of microglial nomenclature for researchers, reviewers, and editors, which will serve as the foundations for a future white paper.

Published
2022

4. Microglia rescue neurons from aggregate-induced neuronal dysfunction and death through tunneling nanotubes

Author

Scheiblich, Hannah, Eikens, Frederik, Wischhof, Lena, Opitz, Sabine, Jüngling, Kay, Cserép, Csaba, Schmidt, Susanne V., Lambertz, Jessica, Bellande, Tracy, Pósfai, Balázs, Geck, Charlotte, Spitzer, Jasper, Odainic, Alexandru, Castro-Gomez, Sergio, Schwartz, Stephanie, Boussaad, Ibrahim, Krüger, Rejko, Glaab, Enrico, Di Monte, Donato A., Bano, Daniele, Dénes, Ádám, Latz, Eike, Melki, Ronald, Pape, Hans-Christian, and Heneka, Michael T.

Published
2024
Full Text
View/download PDF

6. Endothelial cells and macrophages as allies in the healthy and diseased brain

Author

Projekt DEAL, European Commission, Denes, Adam, Hansen, Cathrin E., Oezorhan, Uemit, Figuerola, Sara, Vries, Helga E. de, Sorokin, Lydia, Planas, Anna M., Engelhardt, Britta, Schwaninger, Markus, Projekt DEAL, European Commission, Denes, Adam, Hansen, Cathrin E., Oezorhan, Uemit, Figuerola, Sara, Vries, Helga E. de, Sorokin, Lydia, Planas, Anna M., Engelhardt, Britta, and Schwaninger, Markus

Abstract

Diseases of the central nervous system (CNS) are often associated with vascular disturbances or inflammation and frequently both. Consequently, endothelial cells and macrophages are key cellular players that mediate pathology in many CNS diseases. Macrophages in the brain consist of the CNS-associated macrophages (CAMs) [also referred to as border-associated macrophages (BAMs)] and microglia, both of which are close neighbours or even form direct contacts with endothelial cells in microvessels. Recent progress has revealed that different macrophage populations in the CNS and a subset of brain endothelial cells are derived from the same erythromyeloid progenitor cells. Macrophages and endothelial cells share several common features in their life cycle-from invasion into the CNS early during embryonic development and proliferation in the CNS, to their demise. In adults, microglia and CAMs have been implicated in regulating the patency and diameter of vessels, blood flow, the tightness of the blood-brain barrier, the removal of vascular calcification, and the life-time of brain endothelial cells. Conversely, CNS endothelial cells may affect the polarization and activation state of myeloid populations. The molecular mechanisms governing the pas de deux of brain macrophages and endothelial cells are beginning to be deciphered and will be reviewed here.

Published
2024

7. Perinatal asphyxia leads to acute kidney damage and increased renal susceptibility in adulthood.

Author

Lakat, Tamas, Fekete, Andrea, Demeter, Kornel, Toth, Akos R., Varga, Zoltan K., Patonai, Attila, Kelemen, Hanga, Budai, Andras, Szabo, Miklos, Szabo, Attila J., Kaila, Kai, Denes, Adam, Mikics, Eva, and Hosszu, Adam

Subjects
ASPHYXIA neonatorum, CONNECTIVE tissue growth factor, HEAT stroke, MACHINE learning, RENAL tubular transport disorders, LIPOCALIN-2, HEAT shock factors
Abstract

Perinatal asphyxia (PA) poses a significant threat to multiple organs, particularly the kidneys. Diagnosing PA-associated kidney injury remains challenging, and treatment options are inadequate. Furthermore, there is a lack of long-term follow-up data regarding the renal implications of PA. In this study, 7-day-old male Wistar rats were exposed to PA using a gas mixture (4% O2; 20% CO2 in N2 for 15 min) to investigate molecular pathways linked to renal tubular damage, hypoxia, angiogenesis, heat shock response, inflammation, and fibrosis in the kidney. In a second experiment, adult rats with a history of PA were subjected to moderate renal ischemia-reperfusion (IR) injury to test the hypothesis that PA exacerbates renal susceptibility. Our results revealed an increased gene expression of renal injury markers (kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin), hypoxic and heat shock factors (hypoxia-inducible factor-1α, heat shock factor-1, and heat shock protein-27), proinflammatory cytokines (interleukin-1β, interleukin-6, tumor necrosis factor-α, and monocyte chemoattractant protein-1), and fibrotic markers (transforming growth factor-β, connective tissue growth factor, and fibronectin) promptly after PA. Moreover, a machine learning model was identified through random forest analysis, demonstrating an impressive classification accuracy (95.5%) for PA. Post-PA rats showed exacerbated functional decline and tubular injury and more intense hypoxic, heat shock, proinflammatory, and profibrotic response after renal IR injury compared with controls. In conclusion, PA leads to subclinical kidney injury, which may increase the susceptibility to subsequent renal damage later in life. In addition, the parameters identified through random forest analysis provide a robust foundation for future biomarker research in the context of PA. NEW & NOTEWORTHY: This article demonstrates that perinatal asphyxia leads to subclinical kidney injury that permanently increases renal susceptibility to subsequent ischemic injury. We identified major molecular pathways involved in perinatal asphyxia-induced renal complications, highlighting potential targets of therapeutic approaches. In addition, random forest analysis revealed a model that classifies perinatal asphyxia with 95.5% accuracy that may provide a strong foundation for further biomarker research. These findings underscore the importance of multiorgan follow-up for perinatal asphyxia-affected patients. [ABSTRACT FROM AUTHOR]

Published
2024
Full Text
View/download PDF

11. Viral epidemics in a cell culture: novel high resolution data and their interpretation by a percolation theory based model

Author

Gönci, Balázs, Németh, Valéria, Balogh, Emeric, Szabó, Bálint, Dénes, Ádám, Környei, Zsuzsanna, and Vicsek, Tamás

Subjects
Physics - Biological Physics, Condensed Matter - Statistical Mechanics, Quantitative Biology - Cell Behavior
Abstract

Because of its relevance to everyday life, the spreading of viral infections has been of central interest in a variety of scientific communities involved in fighting, preventing and theoretically interpreting epidemic processes. Recent large scale observations have resulted in major discoveries concerning the overall features of the spreading process in systems with highly mobile susceptible units, but virtually no data are available about observations of infection spreading for a very large number of immobile units. Here we present the first detailed quantitative documentation of percolation-type viral epidemics in a highly reproducible in vitro system consisting of tens of thousands of virtually motionless cells. We use a confluent astroglial monolayer in a Petri dish and induce productive infection in a limited number of cells with a genetically modified herpesvirus strain. This approach allows extreme high resolution tracking of the spatio-temporal development of the epidemic. We show that a simple model is capable of reproducing the basic features of our observations, i.e., the observed behaviour is likely to be applicable to many different kinds of systems. Statistical physics inspired approaches to our data, such as fractal dimension of the infected clusters as well as their size distribution, seem to fit into a percolation theory based interpretation. We suggest that our observations may be used to model epidemics in more complex systems, which are difficult to study in isolation., Comment: To appear in PLoS ONE. Supporting material can be downloaded from http://amur.elte.hu/BDGVirus/

Published
2010
Full Text
View/download PDF

17. Citalopram Neuroendocrine Challenge Shows Altered Tryptophan and Kynurenine Metabolism in Migraine

Author

Gecse, Kinga, primary, Édes, Andrea, additional, Nagy, Tamás, additional, Demeter, Adrienn, additional, Virág, Dávid, additional, Király, Márton, additional, Dalmadi Kiss, Borbála, additional, Ludányi, Krisztina, additional, Környei, Zsuzsanna, additional, Denes, Adam, additional, Bagdy, Gyorgy, additional, and Juhasz, Gabriella, additional

Published
2022
Full Text
View/download PDF

19. Microglia states and nomenclature: A field at its crossroads.

Author

Paolicelli, Rosa C., Sierra, Amanda, Stevens, Beth, Tremblay, Marie-Eve, Aguzzi, Adriano, Ajami, Bahareh, Amit, Ido, Audinat, Etienne, Bechmann, Ingo, Bennett, Mariko, Bennett, Frederick, Bessis, Alain, Biber, Knut, Bilbo, Staci, Blurton-Jones, Mathew, Boddeke, Erik, Brites, Dora, Brône, Bert, Brown, Guy C., Butovsky, Oleg, Carson, Monica J., Castellano, Bernardo, Colonna, Marco, Cowley, Sally A., Cunningham, Colm, Davalos, Dimitrios, De Jager, Philip L., de Strooper, Bart, Denes, Adam, Eggen, Bart J. L., Eyo, Ukpong, Galea, Elena, Garel, Sonia, Ginhoux, Florent, Glass, Christopher K., Gokce, Ozgun, Gomez-Nicola, Diego, González, Berta, Gordon, Siamon, Graeber, Manuel B., Greenhalgh, Andrew D., Gressens, Pierre, Greter, Melanie, Gutmann, David H., Haass, Christian, Heneka, Michael, Heppner, Frank L., Hong, Soyon, Hume, David A., Jung, Steffen, Kettenmann, Helmut, Kipnis, Jonathan, Koyama, Ryuta, Lemke, Greg, Lynch, Marina, Majewska, Ania, Malcangio, Marzia, Malm, Tarja, Mancuso, Renzo, Masuda, Takahiro, Matteoli, Michela, McColl, Barry W., Miron, Veronique E., Molofsky, Anna Victoria, Monje, Michelle, Mracsko, Eva, Nadjar, Agnes, Neher, Jonas J., Neniskyte, Urte, Neumann, Harald, Noda, Mami, Peng, Bo, Peri, Francesca, Perry, V. Hugh, Popovich, Phillip G., Pridans, Clare, Priller, Josef, Prinz, Marco, Ragozzino, Davide, Ransohoff, Richard M., Salter, Michael W., Schaefer, Anne, Schafer, Dorothy P., Schwartz, Michal, Simons, Mikael, Smith, Cody J., Streit, Wolfgang J., Tay, Tuan Leng, Tsai, Li-Huei, Verkhratsky, Alexei, von Bernhardi, Rommy, Wake, Hiroaki, Wittamer, Valérie, Wolf, Susanne A., Wu, Long-Jun, Wyss-Coray, Tony, Paolicelli, Rosa C., Sierra, Amanda, Stevens, Beth, Tremblay, Marie-Eve, Aguzzi, Adriano, Ajami, Bahareh, Amit, Ido, Audinat, Etienne, Bechmann, Ingo, Bennett, Mariko, Bennett, Frederick, Bessis, Alain, Biber, Knut, Bilbo, Staci, Blurton-Jones, Mathew, Boddeke, Erik, Brites, Dora, Brône, Bert, Brown, Guy C., Butovsky, Oleg, Carson, Monica J., Castellano, Bernardo, Colonna, Marco, Cowley, Sally A., Cunningham, Colm, Davalos, Dimitrios, De Jager, Philip L., de Strooper, Bart, Denes, Adam, Eggen, Bart J. L., Eyo, Ukpong, Galea, Elena, Garel, Sonia, Ginhoux, Florent, Glass, Christopher K., Gokce, Ozgun, Gomez-Nicola, Diego, González, Berta, Gordon, Siamon, Graeber, Manuel B., Greenhalgh, Andrew D., Gressens, Pierre, Greter, Melanie, Gutmann, David H., Haass, Christian, Heneka, Michael, Heppner, Frank L., Hong, Soyon, Hume, David A., Jung, Steffen, Kettenmann, Helmut, Kipnis, Jonathan, Koyama, Ryuta, Lemke, Greg, Lynch, Marina, Majewska, Ania, Malcangio, Marzia, Malm, Tarja, Mancuso, Renzo, Masuda, Takahiro, Matteoli, Michela, McColl, Barry W., Miron, Veronique E., Molofsky, Anna Victoria, Monje, Michelle, Mracsko, Eva, Nadjar, Agnes, Neher, Jonas J., Neniskyte, Urte, Neumann, Harald, Noda, Mami, Peng, Bo, Peri, Francesca, Perry, V. Hugh, Popovich, Phillip G., Pridans, Clare, Priller, Josef, Prinz, Marco, Ragozzino, Davide, Ransohoff, Richard M., Salter, Michael W., Schaefer, Anne, Schafer, Dorothy P., Schwartz, Michal, Simons, Mikael, Smith, Cody J., Streit, Wolfgang J., Tay, Tuan Leng, Tsai, Li-Huei, Verkhratsky, Alexei, von Bernhardi, Rommy, Wake, Hiroaki, Wittamer, Valérie, Wolf, Susanne A., Wu, Long-Jun, and Wyss-Coray, Tony

Abstract

Microglial research has advanced considerably in recent decades yet has been constrained by a rolling series of dichotomies such as "resting versus activated" and "M1 versus M2." This dualistic classification of good or bad microglia is inconsistent with the wide repertoire of microglial states and functions in development, plasticity, aging, and diseases that were elucidated in recent years. New designations continuously arising in an attempt to describe the different microglial states, notably defined using transcriptomics and proteomics, may easily lead to a misleading, although unintentional, coupling of categories and functions. To address these issues, we assembled a group of multidisciplinary experts to discuss our current understanding of microglial states as a dynamic concept and the importance of addressing microglial function. Here, we provide a conceptual framework and recommendations on the use of microglial nomenclature for researchers, reviewers, and editors, which will serve as the foundations for a future white paper.

Published
2022

20. Microglia states and nomenclature: A field at its crossroads.

Author

Paolicelli, Rosa RC, Sierra, Amanda, Stevens, Beth, Tremblay, Marie-Eve, Aguzzi, Adriano, Ajami, Bahareh, Amit, Ido, Audinat, Etienne, Bechmann, Ingo, Bennett, Mariko, Bennett, Frederick, Bessis, Alain, Biber, Knut, Bilbo, Staci, Blurton-Jones, Mathew, Boddeke, Erik, Brites, Dora, Brône, Bert, Brown, Guy C, Butovsky, Oleg, Carson, Monica J, Castellano, Bernardo, Colonna, Marco, Cowley, Sally A, Cunningham, Colm, Davalos, Dimitrios, De Jager, Philip L, De Strooper, Bart, Denes, Adam, Eggen, Bart BJL, Eyo, Ukpong, Galea, Elena, Garel, Sonia, Ginhoux, Florent, Glass, Christopher K, Gokce, Ozgun, Gomez-Nicola, Diego, González, Berta, Gordon, Siamon, Graeber, Manuel MB, Greenhalgh, Andrew AD, Gressens, Pierre, Greter, Melanie, Gutmann, David DH, Haass, Christian, Heneka, Michael MT, Heppner, Frank FL, Hong, Soyon, Hume, David DA, Jung, Steffen, Kettenmann, Helmut, Kipnis, Jonathan, Koyama, Ryuta, Lemke, Greg, Lynch, Marina, Majewska, Ania, Malcangio, Marzia, Malm, Tarja, Mancuso, Renzo, Masuda, Takahiro, Matteoli, Michela, McColl, Barry W, Miron, Veronique E, Molofsky, Anna Victoria, Monje, Michelle, Mracsko, Eva, Nadjar, Agnes, Neher, Jonas JJ, Neniskyte, Urte, Neumann, Frank Harald, Noda, Mami, Peng, Bo, Peri, Francesca, Perry, Hugh VH, Popovich, Phillip PG, Pridans, Clare, Priller, Josef, Prinz, Marco, Ragozzino, Davide, Ransohoff, Richard M, Salter, Michael W, Schaefer, Anne, Schafer, Dorothy P, Schwartz, Michal, Simons, Mikael, Smith, Cody J, Streit, Wolfgang WJ, Tay, Tuan Leng, Tsai, Li-Huei, Verkhratsky, Alexei, von Bernhardi, Rommy, Wake, Hiroaki, Wittamer, Valérie, Wolf, Susanne A, Wu, Long-Jun, Wyss-Coray, Tony, Paolicelli, Rosa RC, Sierra, Amanda, Stevens, Beth, Tremblay, Marie-Eve, Aguzzi, Adriano, Ajami, Bahareh, Amit, Ido, Audinat, Etienne, Bechmann, Ingo, Bennett, Mariko, Bennett, Frederick, Bessis, Alain, Biber, Knut, Bilbo, Staci, Blurton-Jones, Mathew, Boddeke, Erik, Brites, Dora, Brône, Bert, Brown, Guy C, Butovsky, Oleg, Carson, Monica J, Castellano, Bernardo, Colonna, Marco, Cowley, Sally A, Cunningham, Colm, Davalos, Dimitrios, De Jager, Philip L, De Strooper, Bart, Denes, Adam, Eggen, Bart BJL, Eyo, Ukpong, Galea, Elena, Garel, Sonia, Ginhoux, Florent, Glass, Christopher K, Gokce, Ozgun, Gomez-Nicola, Diego, González, Berta, Gordon, Siamon, Graeber, Manuel MB, Greenhalgh, Andrew AD, Gressens, Pierre, Greter, Melanie, Gutmann, David DH, Haass, Christian, Heneka, Michael MT, Heppner, Frank FL, Hong, Soyon, Hume, David DA, Jung, Steffen, Kettenmann, Helmut, Kipnis, Jonathan, Koyama, Ryuta, Lemke, Greg, Lynch, Marina, Majewska, Ania, Malcangio, Marzia, Malm, Tarja, Mancuso, Renzo, Masuda, Takahiro, Matteoli, Michela, McColl, Barry W, Miron, Veronique E, Molofsky, Anna Victoria, Monje, Michelle, Mracsko, Eva, Nadjar, Agnes, Neher, Jonas JJ, Neniskyte, Urte, Neumann, Frank Harald, Noda, Mami, Peng, Bo, Peri, Francesca, Perry, Hugh VH, Popovich, Phillip PG, Pridans, Clare, Priller, Josef, Prinz, Marco, Ragozzino, Davide, Ransohoff, Richard M, Salter, Michael W, Schaefer, Anne, Schafer, Dorothy P, Schwartz, Michal, Simons, Mikael, Smith, Cody J, Streit, Wolfgang WJ, Tay, Tuan Leng, Tsai, Li-Huei, Verkhratsky, Alexei, von Bernhardi, Rommy, Wake, Hiroaki, Wittamer, Valérie, Wolf, Susanne A, Wu, Long-Jun, and Wyss-Coray, Tony

Abstract

Microglial research has advanced considerably in recent decades yet has been constrained by a rolling series of dichotomies such as "resting versus activated" and "M1 versus M2." This dualistic classification of good or bad microglia is inconsistent with the wide repertoire of microglial states and functions in development, plasticity, aging, and diseases that were elucidated in recent years. New designations continuously arising in an attempt to describe the different microglial states, notably defined using transcriptomics and proteomics, may easily lead to a misleading, although unintentional, coupling of categories and functions. To address these issues, we assembled a group of multidisciplinary experts to discuss our current understanding of microglial states as a dynamic concept and the importance of addressing microglial function. Here, we provide a conceptual framework and recommendations on the use of microglial nomenclature for researchers, reviewers, and editors, which will serve as the foundations for a future white paper., SCOPUS: re.j, info:eu-repo/semantics/published

Published
2022

23. Brain inflammation is induced by co-morbidities and risk factors for stroke

Author

Drake, Caroline, Boutin, Hervé, Jones, Matthew S., Denes, Adam, McColl, Barry W., Selvarajah, Johann R., Hulme, Sharon, Georgiou, Rachel F., Hinz, Rainer, Gerhard, Alexander, Vail, Andy, Prenant, Christian, Julyan, Peter, Maroy, Renaud, Brown, Gavin, Smigova, Alison, Herholz, Karl, Kassiou, Michael, Crossman, David, Francis, Sheila, Proctor, Spencer D., Russell, James C., Hopkins, Stephen J., Tyrrell, Pippa J., Rothwell, Nancy J., and Allan, Stuart M.

Published
2011
Full Text
View/download PDF

30. Chronic T cell proliferation in brains after stroke could interfere with the efficacy of immunotherapies

Author

Heindl, Steffanie, primary, Ricci, Alessio, additional, Carofiglio, Olga, additional, Zhou, Qihui, additional, Arzberger, Thomas, additional, Lenart, Nikolett, additional, Franzmeier, Nicolai, additional, Hortobagyi, Tibor, additional, Nelson, Peter T., additional, Stowe, Ann M., additional, Denes, Adam, additional, Edbauer, Dieter, additional, and Liesz, Arthur, additional

Published
2021
Full Text
View/download PDF

42. Microglial cell loss after ischemic stroke favors brain neutrophil accumulation

Author

Agencia Estatal de Investigación (España), Ministerio de Economía y Competitividad (España), Ministerio de Ciencia, Innovación y Universidades (España), Otxoa de Amezaga, Amaia, Miró-Mur, Francesc, Pedragosa, Jordi, Gallizioli, Mattia, Justicia, Carles, Gaja-Capdevila, Núria, Ruíz-Jaén, Francisca, Salas-Perdomo, Angélica, Bosch, Anna, Calvo, María, Márquez-Kisinousky, Leonardo, Denes, Adam, Gunzer, Matthias, Planas, Anna M., Agencia Estatal de Investigación (España), Ministerio de Economía y Competitividad (España), Ministerio de Ciencia, Innovación y Universidades (España), Otxoa de Amezaga, Amaia, Miró-Mur, Francesc, Pedragosa, Jordi, Gallizioli, Mattia, Justicia, Carles, Gaja-Capdevila, Núria, Ruíz-Jaén, Francisca, Salas-Perdomo, Angélica, Bosch, Anna, Calvo, María, Márquez-Kisinousky, Leonardo, Denes, Adam, Gunzer, Matthias, and Planas, Anna M.

Abstract

Stroke attracts neutrophils to the injured brain tissue where they can damage the integrity of the blood–brain barrier and exacerbate the lesion. However, the mechanisms involved in neutrophil transmigration, location and accumulation in the ischemic brain are not fully elucidated. Neutrophils can reach the perivascular spaces of brain vessels after crossing the endothelial cell layer and endothelial basal lamina of post-capillary venules, or migrating from the leptomeninges following pial vessel extravasation and/or a suggested translocation from the skull bone marrow. Based on previous observations of microglia phagocytosing neutrophils recruited to the ischemic brain lesion, we hypothesized that microglial cells might control neutrophil accumulation in the injured brain. We studied a model of permanent occlusion of the middle cerebral artery in mice, including microglia- and neutrophil-reporter mice. Using various in vitro and in vivo strategies to impair microglial function or to eliminate microglia by targeting colony stimulating factor 1 receptor (CSF1R), this study demonstrates that microglial phagocytosis of neutrophils has fundamental consequences for the ischemic tissue. We found that reactive microglia engulf neutrophils at the periphery of the ischemic lesion, whereas local microglial cell loss and dystrophy occurring in the ischemic core are associated with the accumulation of neutrophils first in perivascular spaces and later in the parenchyma. Accordingly, microglia depletion by long-term treatment with a CSF1R inhibitor increased the numbers of neutrophils and enlarged the ischemic lesion. Hence, microglial phagocytic function sets a critical line of defense against the vascular and tissue damaging capacity of neutrophils in brain ischemia.

Published
2019

43. Neuronal toll-like receptor 4 signaling induces brain endothelial activation and neutrophil transmigration in vitro

Author

Leow-Dyke Sophie, Allen Charlotte, Denes Adam, Nilsson Olov, Maysami Samaneh, Bowie Andrew G, Rothwell Nancy J, and Pinteaux Emmanuel

Subjects
Neurons, Toll-like receptors, Lipopolysaccharide, Neutrophils, Chemokines, Endothelial cells, Neurology. Diseases of the nervous system, RC346-429
Abstract

Abstract Background The innate immune response in the brain is initiated by pathogen-associated molecular patterns (PAMPS) or danger-associated molecular patterns (DAMPS) produced in response to central nervous system (CNS) infection or injury. These molecules activate members of the Toll-like receptor (TLR) family, of which TLR4 is the receptor for bacterial lipopolysaccharide (LPS). Although neurons have been reported to express TLR4, the function of TLR4 activation in neurons remains unknown. Methods TLR4 mRNA expression in primary mouse glial and neuronal cultures was assessed by RT-PCR. Mouse mixed glial, neuronal or endothelial cell cultures were treated with LPS in the absence or the presence of a TLR4 specific antagonist (VIPER) or a specific JNK inhibitor (SP600125). Expression of inflammatory mediators was assayed by cytometric bead array (CBA) and ELISA. Activation of extracellular-signal regulated kinase 1/2 (ERK1/2), p38, c-Jun-N-terminal kinase (JNK) and c-Jun was assessed by Western blot. The effect of conditioned media of untreated- versus LPS-treated glial or neuronal cultures on endothelial activation was assessed by neutrophil transmigration assay, and immunocytochemistry and ELISA were used to measure expression of intercellular cell adhesion molecule (ICAM-1) and vascular cell adhesion molecule (VCAM-1). Results LPS induces strong release of the chemokines RANTES and CXCL1 (KC), tumor necrosis factor-α (TNFα) and IL-6 in primary mouse neuronal cultures. In contrast, LPS induced release of IL-1α, IL-1β and granulocyte-colony stimulating factor (G-CSF) in mixed glial, but not in neuronal cultures. LPS-induced neuronal KC expression and release were completely blocked by VIPER. In glial cultures, LPS induced activation of ERK1/2, p38 and JNK. In contrast, in neuronal cultures, LPS activated JNK but not ERK1/2 or p38, and the specific JNK inhibitor SP600125 significantly blocked LPS-induced KC expression and release. Finally, conditioned medium of LPS-treated neuronal cultures induced strong expression of ICAM-1 and VCAM-1 on endothelial cells, and induced infiltration of neutrophils across the endothelial monolayer, which was inhibited by VIPER. Conclusion These data demonstrate for the first time that neurons can play a role as key sensors of infection to initiate CNS inflammation.

Published
2012
Full Text
View/download PDF

44. Interleukin-1 mediates ischaemic brain injury via distinct actions on endothelial cells and cholinergic neurons

Author

Wong, Raymond, Lénárt, Nikolett, Hill, Laura, Toms, Lauren, Martinecz, Bernadett, Császár, Eszter, Nyiri, Gábor, Papaemmanouil, Athina, Waisman, Ari, Muller, Werner, Schwaninger, Markus, Rothwell, Nancy, Francis, Sheila, Pinteaux, Emmanuel, Denes, Adam, and Allan, Stuart

Abstract

The cytokine interleukin-1 (IL-1) is a key contributor to neuroinflammation and brain injury, yet mechanisms by which IL-1 triggers neuronal injury remain unknown. Here we induced conditional deletion of IL-1R1 in brain endothelial cells, neurons and blood cells to assess site-specific IL-1 actions in a model of cerebral ischaemia in mice. Tamoxifen treatment of IL-1R1 floxed (fl/fl) mice crossed with mice expressing tamoxifen-inducible Cre-recombinase under the Slco1c1 promoter resulted in brain endothelium-specific deletion of IL-1R1 and a significant decrease in infarct size (29%), blood-brain barrier (BBB) breakdown (53%) and neurological deficit (40%) compared to vehicle-treated or control (IL-1R1fl/fl) mice. Absence of brain endothelial IL-1 signalling improved cerebral blood flow, followed by reduced neutrophil infiltration and vascular activation 24 h after brain injury. Conditional IL-1R1 deletion in neurons using tamoxifen inducible nestin-Cre mice resulted in reduced neuronal injury (25%) and altered microglia-neuron interactions, without affecting cerebral perfusion or vascular activation. Deletion of IL-1R1 specifically in cholinergic neurons reduced infarct size, brain oedema and improved functional outcome. Ubiquitous deletion of IL-1R1 had no effect on brain injury, suggesting beneficial compensatory mechanisms on other cells against the detrimental effects of IL-1 on endothelial cells and neurons. We also show that IL-1R1 signalling deletion in platelets or myeloid cells does not contribute to brain injury after experimental stroke. Thus, brain endothelial and neuronal (cholinergic) IL-1R1 mediate detrimental actions of IL-1 in the brain in ischaemic stroke. Cell-specific targeting of IL-1R1 in the brain could therefore have therapeutic benefits in stroke and other cerebrovascular diseases.

Published
2018

46. Interleukin-1α expression precedes IL-1β after ischemic brain injury and is localised to areas of focal neuronal loss and penumbral tissues

Author

Luheshi Nadia M, Kovács Krisztina J, Lopez-Castejon Gloria, Brough David, and Denes Adam

Subjects
Neurology. Diseases of the nervous system, RC346-429
Abstract

Abstract Background Cerebral ischemia is a devastating condition in which the outcome is heavily influenced by inflammatory processes, which can augment primary injury caused by reduced blood supply. The cytokines interleukin-1α (IL-1α) and IL-1β are key contributors to ischemic brain injury. However, there is very little evidence that IL-1 expression occurs at the protein level early enough (within hours) to influence brain damage after stroke. In order to determine this we investigated the temporal and spatial profiles of IL-1α and IL-1β expression after cerebral ischemia. Findings We report here that in mice, as early as 4 h after reperfusion following ischemia induced by occlusion of the middle cerebral artery, IL-1α, but not IL-1β, is expressed by microglia-like cells in the ischemic hemisphere, which parallels an upregulation of IL-1α mRNA. 24 h after ischemia IL-1α expression is closely associated with areas of focal blood brain barrier breakdown and neuronal death, mostly near the penumbra surrounding the infarct. The sub-cellular distribution of IL-1α in injured areas is not uniform suggesting that it is regulated. Conclusions The early expression of IL-1α in areas of focal neuronal injury suggests that it is the major form of IL-1 contributing to inflammation early after cerebral ischemia. This adds to the growing body of evidence that IL-1α is a key mediator of the sterile inflammatory response.

Published
2011
Full Text
View/download PDF

47. Microglial cell loss after ischemic stroke favors brain neutrophil accumulation

Author

Otxoa-de-Amezaga, Amaia, primary, Miró-Mur, Francesc, additional, Pedragosa, Jordi, additional, Gallizioli, Mattia, additional, Justicia, Carles, additional, Gaja-Capdevila, Núria, additional, Ruíz-Jaen, Francisca, additional, Salas-Perdomo, Angélica, additional, Bosch, Anna, additional, Calvo, Maria, additional, Márquez-Kisinousky, Leonardo, additional, Denes, Adam, additional, Gunzer, Matthias, additional, and Planas, Anna M., additional

Published
2018
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results