Global ETD Search

1	Myeloid cell involvement during the resolution of acute brain inflammation Davies, Claire Linzi January 2016 (has links) Excessive tissue-damaging inflammation can exacerbate acute brain injury, and non-resolving inflammation is implicated in chronic neurodegeneration. Understanding the mechanisms that resolve deleterious inflammation in the brain is imperative to develop new therapeutic strategies. However current knowledge is limited, partly due to a lack of tractable models. Studies in extra-cerebral tissues have shown that myeloid cells are central to the inflammatory response. The aim of this thesis was to develop a model of self-limiting acute brain inflammation that is optimised to address mechanisms controlling resolution. The model was used to define the temporal profile of myeloid cell accumulation in the brain and establish the precise identities, origin and functional contribution of cell subsets in the resolution of the inflammatory response in the brain. Cerebral inflammation was induced by stereotaxic injection of inflammatory stimuli (LPS, HMGB1, MSU); LPS produced a robust inflammatory response and neutrophil influx and loss defined clear phases of initiation and resolution. Cellular changes (e.g. glial activation, endothelial activation and leukocyte influx) in response to LPS were characteristic of acute inflammation. Bone marrow chimaeric (Csf1r-EGFPC57Bl/6J) and monocyte reporter (Ccr2+/RFP) mice were used to distinguish between infiltrating macrophages and resident microglia. Analysis over 28 d showed the temporal profile of myeloid cells during brain inflammation, and monocyte accumulation contributed to expansion of the total mononuclear phagocyte population. Ccr2RFP/RFP knock-in mice showed that monocyte recruitment and resolution were independent of CCR2, and selective depletion of Ly6Clo monocytes with an anti- CSF1R antibody did not affect macrophage recruitment. Monocyte depletion using clodronate failed to deplete the Ly6Cint population and monocytes were still recruited into the brain. Together these results suggest multiple monocyte subsets could be involved in the inflammatory response in the brain. These data show that myeloid cell subsets of distinct origins accumulate in the inflamed brain. This work establishes a model system to identify endogenous mechanisms of resolution in cerebral inflammation and provides a platform to test CNS-targeted pro-resolution agents.
2	The effect of hypoxia on macrophage proteoglycans : potential role in atherosclerosis / Asplund, Annika, January 2009 (has links) Diss. (sammanfattning) Göteborg : Göteborgs universitet, 2009. / Härtill 3 uppsatser.
3	The Diversity and Functions of Microglia/Macrophages in Neurological Disease and Glioma Microenvironment Rajagopalan, Shanmuga Priya January 2022 (has links) No description available. Cellular Biology Microglia Brain macrophages Neurological disease Glioma tumor-microenvironment Tumor associated macrophages
4	La migration des microglies et les molécules adhésives au cours du développement embryonnaire du cerveau / Microglial migration and adhesion molecules during embryonic brain development Smolders, Sophie 30 October 2017 (has links) Les microglies sont des cellules hématogène mais prennent place dans le système nerveux central (SNC) au cours du développement embryonnaire pour constituer la population résidente des cellules immunitaires. Elles sont les médiateurs crucials du bon développement et de l'entretien des réseaux de neurones dans le SNC. De nombreux aspects de la physiologie microgliale et les mécanismes qui sous-tendent leurs fonctions au cours du développement embryonnaire du cerveau sont encore largement méconnues. Cette thèse de doctorat porte sur la migration des cellules microgliales au cours du développement embryonnaire du cortex et elle débouche sur trois grandes conclusions. (1) Les cellules microgliales embryonnaires in situ sont très dynamiques et adaptent leur phénotype à leur environnement local. (2) La vitesse de migration des microglies ex vivo dépend des intégrines beta1 qui exercent des fonctions à la fois inhibitrices et promotrices sur la migration selon l'âge embryonnaire. (3) Les microglies jouent probablement un rôle dans l'étiologie des troubles du développement neurologique, mais il faudrait que les futures recherches se concentrent sur le dysfonctionnement des microglies plutôt que sur leur activation immunitaire classique. / Microglia are blood-borne cells but take up residence in the central nervous system (CNS) during embryonic development to constitute the resident pool of immune cells. They are crucial mediators of the healthy development and maintenance of neural networks in the CNS. Many aspects of the physiology of microglia and the mechanisms underpinning their tasks during embryonic brain development are still unresolved. This doctoral dissertation focuses on migration of microglial cells during embryonic cortical development. All together, this dissertation brings forwards three major conclusions. (1) In situ embryonic microglia are highly dynamic cells that adapt their phenotype to their local environment. (2) Microglial migration speed ex vivo is dependent on β1 integrins that exert both migration promoting and inhibiting functions which are age-specifically regulated. (3) Microglia likely play a role in the etiology of neurodevelopmental disorders, but further research should focus on microglia dysfunction rather than classical microglial immune activation. Matrice extracellulaire Integrines Migration cellulaire Inflammation maternelle Développement Souris Macrophages du cerveau Vaisseaux sanguins Extracellular matrix Brain macrophages Development 612.82
5	Etude de l'implication des cellules microgliales et de l'α-synucleine dans la maladie neurodégénérative de Parkinson / Microglia and α-synuclein implication in Parkinson's disease Moussaud, Simon 25 February 2011 (has links) Les maladies neurodégénératives liées à l’âge, telle celle de Parkinson, sont un problème majeur de santé publique. Cependant, la maladie de Parkinson reste incurable et les traitements sont très limités. En effet, les causes de la maladie restent encore mal comprises et la recherche se concentre sur ses mécanismes moléculaires. Dans cette étude, nous nous sommes intéressés à deux phénomènes anormaux se produisant dans la maladie de Parkinson : l’agrégation de l’α-synucléine et l’activation des cellules microgliales. Pour étudier la polymérisation de l’α-synucléine, nous avons établi de nouvelles méthodes permettant la production in vitro de différents types d’oligomères d’α-synucléine. Grâce à des méthodes biophysiques de pointe, nous avons caractérisé ces différents oligomères à l’échelle moléculaire. Puis nous avons étudié leurs effets toxiques sur les neurones. Ensuite, nous nous sommes intéressés à l’activation des microglies et en particulier à leurs canaux potassiques et aux changements liés au vieillissement. Nous avons identifié les canaux Kv1.3 et Kir2.1 et montré qu’ils étaient impliqués dans l’activation des microglies. En parallèle, nous avons établi une méthode originale qui permet l’isolation et la culture de microglies primaires issues de cerveaux adultes. En comparaison à celles de nouveaux-nés, les microglies adultes montrent des différences subtiles mais cruciales qui soutiennent l’hypothèse de changements liés au vieillissement. Globalement, nos résultats suggèrent qu’il est possible de développer de nouvelles approches thérapeutiques contre la maladie de Parkinson en modulant l’action des microglies ou en bloquant l’oligomérisation de l’ α-synucléine. / Age-related neurodegenerative disorders like Parkinson’s disease take an enormous toll on individuals and on society. Despite extensive efforts, Parkinson’s disease remains incurable and only very limited treatments exist. Indeed, Parkinson’s pathogenesis is still not clear and research on its molecular mechanisms is ongoing. In this study, we focused our interest on two abnormal events occurring in Parkinson’s patients, namely α-synuclein aggregation and microglial activation. We first investigated α-synuclein and its abnormal polymerisation. For this purpose, we developed novel methods, which allowed the in vitro production of different types of α-synuclein oligomers. Using highly sensitive biophysical methods, we characterised these different oligomers at a single-particle level. Then, we tested their biological effects on neurons. Afterwards, we studied microglial activation. We concentrated our efforts on two axes, namely age-related changes in microglial function and K+ channels in microglia. We showed that Kv1.3 and Kir2.1 K+ channels are involved in microglial activation. In parallel, we developed a new approach, which allows the effective isolation and culture of primary microglia from adult mouse brains. Adult primary microglia presented subtle but crucial differences in comparison to microglia from neo-natal mice, confirming the hypothesis of age-related changes of microglia. Taken together, our results support the hypotheses that microglial modulation or inhibition of α-synuclein oligomerisation are possible therapeutic strategies against Parkinson's disease. Vieillissement Maladies neurodégénératives Maladie de Parkinson Neurodégénération Α-synucléine Oligomères Toxicité Dopamine Neurones Neuroinflammation Microglies Immunité du cerveau Lignée cellulaire C8-B4 Cultures primaires Méthode d’isolation in vitro Patch-clamp Electrophysiologie Canaux potassiques Kv1.3 - Kir2.1 Oxyde nitrique Cytokines Aging Neurodegenerative disorders Parkinson’s disease Neurodegeneration Α-synuclein Oligomers Toxicity Dopamine Neurons Neuroinflammation Microglia Brain macrophages Brain immunity C8-B4 cell line Primary culture In vitro isolation method Patch-clamp Electrophysiology Potassium channels Kv1.3 - Kir2.1 Nitric oxide Cytokines 612 616.9

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