Olson Linus, Faulkner Stuart, Lundströmer Karin, Kerenyi Aron, Kelen Dorka, Chandrasekaran M, Ådén Ulrika, Olson Lars, Golay Xavier, Lagercrantz Hugo, Robertson Nicola J, Galter Dagmar
Department of Women's and Children's Health, Astrid Lindgren Children's Hospital, Karolinska Institutet, 17176, Stockholm, Sweden,
Transl Stroke Res. 2013 Apr;4(2):248-57. doi: 10.1007/s12975-012-0215-4. Epub 2012 Oct 14.
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.
低温可降低窒息新生儿的神经发育障碍。然而，神经保护的最佳降温温度尚未明确界定。我们研究了新生仔猪短暂性脑缺氧缺血（HI）对八个基因转录活性的影响，以及全身降温至35、33.5或30°C是否能抵消mRNA水平的变化。BDNF mRNA在损伤后整体上调，且没有一个降温温度能抵消这种变化。相比之下，MANF mRNA下调，33.5°C的低温处理在不同脑区适度抵消了这些变化，而30°C则加剧了MANF mRNA的丢失。除纹状体外，所有脑区的MAP2 mRNA均显著下调，降温至33.5°C适度抵消了大脑皮质的这种下调。在核心区而非被膜区，GFAP mRNA水平有下调趋势，降温至33.5或35°C适度抵消了这些变化。降温至30°C导致GFAP mRNA整体下降。HSP70 mRNA在HI后有上调趋势，在降温至33.5°C时，在海马体皮质和CA1区更为明显。我们得出结论，HI导致新生仔猪浅表和深部脑区许多基因的mRNA水平发生改变。其中一些变化可能是有益的，另一些则是有害的，降低体温部分抵消了一些但不是所有的变化。核心区和被膜区之间以及不同降温温度之间可能存在一般差异。比较三个研究温度，降温至33.5°C似乎能提供最佳的降温温度平衡点。
