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Comparison of Three Hypothermic Target Temperatures for the Treatment of Hypoxic Ischemia: mRNA Level Responses of Eight Genes in the Piglet Brain

机译:三种低温治疗低氧缺血性目标温度的比较:仔猪脑中八个基因的mRNA水平响应

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Hypothermia can reduce neurodevelopmental disabilities in asphyxiated newborn infants. However, the optimal cooling temperature for neuroprotection is not well defined. We studied the effects of transient piglet brain hypoxic ischemia (HI) on transcriptional activity of eight genes and if mRNA level alterations could be counteracted by whole body cooling to 35, 33.5 or 30 °C. BDNF mRNA was globally upregulated by the insult, and none of the cooling temperatures counteracted this change. In contrast, MANF mRNA was downregulated, and these changes were modestly counteracted in different brain regions by hypothermic treatment at 33.5 °C, while 30 °C aggravated the MANF mRNA loss. MAP2 mRNA was markedly downregulated in all brain regions except striatum, and cooling to 33.5 °C modestly counteract this downregulation in the cortex cerebri. There was a tendency for GFAP mRNA levels in core, but not mantle regions to be downregulated and for these changes to be modestly counteracted by cooling to 33.5 or 35 °C. Cooling to 30 °C caused global GFAP mRNA decrease. HSP70 mRNA tended to become upregulated by HI and to be more pronounced in cortex and CA1 of hippocampus during cooling to 33.5 °C. We conclude that HI causes alterations of mRNA levels of many genes in superficial and deep piglet brain areas. Some of these changes may be beneficial, others detrimental, and lowering body temperature partly counteracts some, but not all changes. There may be general differences between core and mantle regions, as well as between the different cooling temperatures for protection. Comparing the three studied temperatures, cooling to 33.5 °C, appears to provide the best cooling temperature compromise.
机译:低体温可以减少窒息新生儿的神经发育障碍。但是,对于神经保护的最佳冷却温度尚不明确。我们研究了短暂性仔猪脑缺氧缺血(HI)对八个基因转录活性的影响,以及是否可以通过将全身冷却至35、33.5或30°C来抵消mRNA水平的改变。 BDNF mRNA被该损伤整体上调,并且没有冷却温度抵消该变化。相比之下,MANF mRNA的表达下调,在33.5°C进行低温治疗可在不同的大脑区域适度抵消这些变化,而30°C则加剧了MANF mRNA的损失。 MAP2 mRNA在纹状体以外的所有大脑区域均显着下调,冷却至33.5°C适度抵消了大脑皮层的这种下调。核心中的GFAP mRNA水平存在趋势,但下皮区域没有被下调,冷却至33.5或35°C可以适度抵消这些变化。冷却至30°C会导致全局GFAP mRNA下降。 HSP70 mRNA倾向于被HI上调,并在冷却至33.5°C时在海马的皮质和CA1中更为明显。我们得出的结论是,HI会引起浅表和深部仔猪脑区域许多基因的mRNA水平改变。这些变化中的某些变化可能是有益的,而另一些则是有害的,降低体温会部分抵消某些变化,但不是全部。核心区域和外套区域之间以及用于保护的不同冷却温度之间可能存在一般差异。比较三个研究温度,冷却至33.5°C,似乎可以提供最佳的冷却温度折衷。

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