PMC:3312845 / 3929-5911 JSONTXT

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TNF-α is expressed at low levels in normal brain and is rapidly upregulated in glia, neurons and endothelial cells in various pathophysiological conditions, including SE [17,18]. TNF-α shows various effects on brain function depending on its local tissue concentration, the type of target cells, and especially the specific receptor subtype: TNF receptor I, or p55 receptor (TNFp55R); and TNF receptor II, or p75 receptor (TNFp75R) [19]. Furthermore, TNF-α induces macrophage inflammatory protein-2 (MIP-2) that recruits neutrophils under pathological conditions, including SE [14,20]. Neurons, microglia, and astrocytes produce MIP-2 when incubated with pro-inflammatory cytokines such as TNF-α and/or interleukin-1β (IL-1β) or after injury [21-23]. Indeed, we have recently reported that SE-mediated MIP-2 expression is relevant to leukocyte infiltrations following SE in an IL-1β-independent manner [20]. However, the relationship between the TNF-α system and BBB disruption/neutrophil infiltration during vasogenic edema formation induced by epileptogenic insults has not been fully clarified. Therefore, in the present study, we investigated the roles of TNF-α in vasogenic edema and its related events in rat epilepsy models provoked by pilocarpine-induced 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