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Articles by Anja Urbach in JoVE
Other articles by Anja Urbach on PubMed
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Expanding Expression of the 5-lipoxygenase Pathway Within the Arterial Wall During Human Atherogenesis
Proceedings of the National Academy of Sciences of the United States of America.
Feb, 2003 |
Pubmed ID: 12552108 Oxidation products of low-density lipoproteins have been suggested to promote inflammation during atherogenesis, and reticulocyte-type 15-lipoxygenase has been implicated to mediate this oxidation. In addition, the 5-lipoxygenase cascade leads to formation of leukotrienes, which exhibit strong proinflammatory activities in cardiovascular tissues. Here, we studied both lipoxygenase pathways in human atherosclerosis. The 5-lipoxygenase pathway was abundantly expressed in arterial walls of patients afflicted with various lesion stages of atherosclerosis of the aorta and of coronary and carotid arteries. 5-lipoxygenase localized to macrophages, dendritic cells, foam cells, mast cells, and neutrophilic granulocytes, and the number of 5-lipoxygenase expressing cells markedly increased in advanced lesions. By contrast, reticulocyte-type 15-lipoxygenase was expressed at levels that were several orders of magnitude lower than 5-lipoxygenase in both normal and diseased arteries, and its expression could not be related to lesion pathology. Our data support a model of atherogenesis in which 5-lipoxygenase cascade-dependent inflammatory circuits consisting of several leukocyte lineages and arterial wall cells evolve within the blood vessel wall during critical stages of lesion development. They raise the possibility that antileukotriene drugs may be an effective treatment regimen in late-stage disease.
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Microarray-based Long-term Detection of Genes Differentially Expressed After Cortical Spreading Depression
The European Journal of Neuroscience.
Aug, 2006 |
Pubmed ID: 16930413 Spreading depression (SD) is a slowly propagating wave of neuronal depolarization altering ion homeostasis, blood flow and energy metabolism without causing irreversible damage of the tissue. As SD has been implicated in several neurological diseases including migraine and stroke, understanding these disorders requires systematic knowledge of the processes modified by SD. Thus, we induced repetitive SD in the rat cerebral cortex by topical application of 3 m KCl for approximately 2 h and evaluated the kinetics of SD-induced changes in cortical gene expression for up to 30 days using Affymetrix RAE230A arrays. The temporal profile showed a rapid expression of immediate early genes, genes associated with inflammation, metabolism, stress and DNA repair, ion transport, and genes that play a role in growth/differentiation. Stress-response genes could still be detected after 24 h. At this time, induced genes were mainly related to the cell membrane and adhesion, or to the cytoskeleton. A subset of genes was still affected even 30 days after SD. Real-time polymerase chain reactions and immunohistochemistry confirmed the microarray results for several of the transcripts. Our findings demonstrate a temporal pattern of gene expression which might promote tissue remodeling and cortical plasticity, and might probably account for the mediation of neuronal tolerance towards subsequent ischemia.
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Cyclin D2 Knockout Mice with Depleted Adult Neurogenesis Learn Barnes Maze Task
Behavioral Neuroscience.
Feb, 2013 |
Pubmed ID: 23244288 There is a broad discussion concerning the function of new neurons in the adult brain. An increasingly accepted hypothesis proposes their crucial role in spatial learning. In this work, however, we demonstrate adult cyclin D2 knockout (cD2 KO) mice, which lack adult hippocampal neurogenesis, are able to learn a spatial version of the Barnes maze. Similar to wild type (WT) controls, these mutant mice exhibited several indicators of learning during 6 days of training: successively shorter latency and distance, higher speed, and decreasing number of errors. WT and cD2 KO mice showed improved search strategies, which became increasingly spatial. During probe Trial 1, mutant mice attained the highest significant number of nose-pokes at the former target hole compared with all the other holes. Both WT and cD2 KO mice covered shorter distances during probe Trial 2, whereas the mutant mice showed higher speed. We also discuss the possibility that some of the observed differences displayed by cD2 KO mice during training and at the probe trials-for example, longer mean distance and more errors-are associated with a smaller hippocampal formation. Our results suggest that adult brain neurogenesis is not obligatory for learning the Barnes maze.
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Cortical Spreading Depolarization Stimulates Gliogenesis in the Rat Entorhinal Cortex
Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism.
2015 |
Pubmed ID: 25515215 Recently, we showed that cortical spreading depolarizations (CSDs) are a potent trigger of hippocampal neurogenesis. Here, we evaluated CSD-induced cytogenesis in the entorhinal cortex (EC), which provides the major afferent input to the dentate gyrus. Cortical spreading depolarizations were induced by epidural application of 3 mol/L KCl, controls received equimolar NaCl. Cytogenesis was analyzed at different time points thereafter by means of intraperitoneal 5-bromodeoxyuridine injections (day 2, 4, or days 1 to 7) and immunohistochemistry. Recurrent CSD significantly increased numbers of newborn cells in the ipsilateral EC. The majority of these cells expressed glial markers. Microglia proliferation was maximal at day 2, whereas NG2 glia and astrocytes responded for a prolonged period of time (days 2 to 4). Newborn glia remained detectable for 6 weeks after CSD. Whereas we furthermore detected newborn cells immunopositive for doublecortin, a marker for immature neuronal cells, we found no evidence for the generation of new neurons in the EC. Our results indicate that CSD is a potent gliogenic stimulus, leading to rapid and enduring changes in the glial cellular composition of the affected brain tissue. Thus, CSD facilitates ongoing structural remodeling of the directly affected cortex that might contribute to the pathophysiology of CSD-related brain pathologies.
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