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  To control for any possible variations between litters, agonist preparation or inoculations

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hu123456
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Počet príspevkov : 254
Registration date : 14.03.2014

 To control for any possible variations between litters, agonist preparation or inoculations Empty
OdoslaťPredmet: To control for any possible variations between litters, agonist preparation or inoculations    To control for any possible variations between litters, agonist preparation or inoculations Icon_minitimeUt júl 01, 2014 7:08 am

The higher ex pression of SLAMF7, CD11a, F4 80 and CD172a on neonatal microglia 17-AAG 分子量 compared with weanling microglia indicates a clear phenotype on these cells that correlates with the heightened inflammatory response in the CNS. Discussion In the current study, we observed heightened responses to TLR stimulation in the CNS in neonatal mice com pared with weanlings. This response was most notable with LPS, but was also observed with CpG ODNs. Kinetic analysis of gene expression indicated that the increased cytokine response in neonates peaked at 6 hpi, which was associated with an increase in activation markers for myeloid cells in the CNS. Analysis of this cell population in the brains of neonatal and weanling mice indicated two primary differences in the myeloid population between these ages.<br><br> The first was more mac rophages 17-DMAG ic50 in weanling mice and the second was increased expression of multiple regulatory molecules on neonatal microglia. Surprisingly, SLAMF7, a regulatory molecule on NK cells, was detected on neonatal, microglia and the mRNA expression of this molecule tightly corre lated with cytokine induction. The increased cytokine expression following TLR stimulation in neonates in the brain is opposite of the activation of monocytes macrophages in the periphery. For example, neonatal mouse monocytes macrophages have reduced cytokine responses to TLR4 stimulation compared with adults, with the exception of IL 10 pro duction. Similar age related effects were also ob served in studies with human monocytes macrophages.<br><br> The primary reason for the differences in the periphery compared with the CNS may simply be the requirement for microglia in the CNS to be active in neonates for synaptic pruning and other developmental processes. A similar role in development has not been reported for peripheral monocytes. Thus, unlike adult animals A66 価格 in which the immune response in the CNS is considered to be more limited than in peripheral tissues, the CNS in neonatal mice may be more responsive to in sult or injury and produce a more substantial inflamma tory response. Since development of the neonatal mouse brain corresponds in several parameters with the second trimester development of the human brain, this time period in humans may be particularly sensitive to immune stimulation.<br><br> However, since myeloid cells ap pear to be responsible for this increased inflammatory response, the inflammatory response in the human brain will most likely correlate with the timeframe in which these cells are most active during development, which may differ from that observed in mice. The elevated response by the myeloid population in the neonatal CNS is surprising considering the lower level of Tlr mRNA expression and the higher levels of inhibitory molecules, including CD200R and CD172a. Deficiency in CD200R has been linked to increased inflammation in models of experi mental autoimmune encephalitis and Parkinsons disease, while CD172a negatively regulates CD11b mediated adhesion, migration and phagocytosis. The higher expression of these receptors would predict a reduced responsiveness to TLR stimulation.
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