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Our aim was to test whether some physiological circumstances, such as stress, could enhance susceptibility to inflammation in the prefrontal cortex (PFC), which shows a relative resistance to inflammation. PFC is important in many brain functions and is a target for some neurodegenerative diseases. We induced an inflammatory process by a single intracortical injection of 2 \u03bcg of lipopolysaccharide (LPS), a potent proinflammogen, in nonstressed and stressed rats. We evaluated the effect of our treatment on inflammatory markers, neuronal populations, BDNF expression, and behavior of several mitogen-activated protein (MAP) kinases and the transcription factor cAMP response element-binding protein. Stress strengthens the changes induced by LPS injection: microglial activation and proliferation with an increase in the levels of the proinflammatory cytokine tumor necrosis factor-\u03b1; loss of cells such as astroglia, seen as loss of glial fibrillary acidic protein immunoreactivity, and neurons, studied by neuronal-specific nuclear protein immunohistochemistry and GAD67 and NMDA receptor 1A mRNAs expression by<jats:italic>in situ<\/jats:italic>hybridization. A significant increase in the BDNF mRNA expression and modifications in the levels of MAP kinase phosphorylation were also found. In addition, we observed a protective effect from RU486 [mifepristone (11\u03b2-[<jats:italic>p<\/jats:italic>-(dimethylamino)phenyl]-17\u03b2-hydroxy-17-(1-propynyl)estra-4,9-dien-3-one)], a potent inhibitor of the glucocorticoid receptor activation. All of these data show a synergistic effect between inflammation and stress, which could explain the relationship described between stress and some neurodegenerative pathologies.<\/jats:p>","DOI":"10.1523\/jneurosci.0802-06.2006","type":"journal-article","created":{"date-parts":[[2006,5,24]],"date-time":"2006-05-24T20:59:33Z","timestamp":1148504373000},"page":"5709-5719","source":"Crossref","is-referenced-by-count":197,"title":["Stress Increases Vulnerability to Inflammation in the Rat Prefrontal Cortex"],"prefix":"10.1523","volume":"26","author":[{"given":"R. M.","family":"de Pablos","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. F.","family":"Villar\u00e1n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Arg\u00fcelles","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. 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