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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
KTH, School of Chemical Science and Engineering (CHE), Chemical Engineering and Technology, Energy Processes.
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2013 (English)In: Translational Stroke Research, ISSN 1868-4483, Vol. 4, no 2, 248-257 p.Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2013. Vol. 4, no 2, 248-257 p.
Keyword [en]
Hypoxic ischemic encephalopathy, In situ hybridisation, Neonatal asphyxia, Neuronal and glial markers, Piglets, Therapeutic hypothermia
National Category
Medical and Health Sciences
URN: urn:nbn:se:kth:diva-120756DOI: 10.1007/s12975-012-0215-4ISI: 000316399200013ScopusID: 2-s2.0-84875056233OAI: diva2:616299
Swedish Research Council

QC 20130416

Available from: 2013-04-16 Created: 2013-04-16 Last updated: 2013-04-22Bibliographically approved

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