![]() Moreover, upregulation of Mef2C in aged mice restrained postoperative microglial activation, attenuating the neuroinflammatory response and cognitive impairment. In vitro, BV2 cells lacking Mef2C released higher levels of inflammatory cytokines upon stimulation with lipopolysaccharide (LPS, a bacterial toxin) than Mef2C-sufficient cells. Knocking down Mef2C induced a microglial priming phenotype in young mice, resulting in postoperative increases in the hippocampal levels of the inflammatory factors IL1-β, IL-6 and TNF-α that could impair cognition these findings were consistent with the observations in aged mice. Notably, the expression of myocyte-specific enhancer 2C (Mef2C), an immune checkpoint that limits overactivation of microglia, was downregulated in aged microglia. Furthermore, microglial depletion by feeding of a standard diet containing a colony stimulating factor 1 receptor (CSF1R) inhibitor (PLX5622) markedly protected aged mice from POCD. We found here that exploratory laparotomy induced cognitive function decline in aged mice but not in young mice and that this decline was accompanied by inflammatory activation of microglia in the hippocampus. ![]() The aim of this study was to explore the mechanisms by which POCD preferentially affects older individuals. Postoperative cognitive dysfunction (POCD) is a common postoperative central nervous system (CNS) complication with a higher occurrence among aged individuals than among young individuals. ![]()
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