naa a22 4500 510776329 CHVBK 20180411083231.0 cr unu---uuuuu 180411e20130401xx s 000 0 eng 10.1007/s12975-012-0215-4 doi (NATIONALLICENCE)springer-10.1007/s12975-012-0215-4 Comparison of Three Hypothermic Target Temperatures for the Treatment of Hypoxic Ischemia: mRNA Level Responses of Eight Genes in the Piglet Brain [Elektronische Daten] [Linus Olson, Stuart Faulkner, Karin Lundströmer, Aron Kerenyi, Dorka Kelen, M. Chandrasekaran, Ulrika Ådén, Lars Olson, Xavier Golay, Hugo Lagercrantz, Nicola Robertson, Dagmar Galter] 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. Springer Science+Business Media New York, 2012 Neonatal asphyxia nationallicence Hypoxic ischemic encephalopathy nationallicence Therapeutic hypothermia nationallicence Neuronal and glial markers nationallicence In situ hybridisation nationallicence Piglets nationallicence Olson Linus Department of Women's and Children's Health, Astrid Lindgren Children's Hospital, Karolinska Institutet, 17176, Stockholm, Sweden aut Faulkner Stuart Institute for Women's Health, University College London, London, UK aut Lundströmer Karin Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden aut Kerenyi Aron Institute for Women's Health, University College London, London, UK aut Kelen Dorka Institute for Women's Health, University College London, London, UK aut Chandrasekaran M. Institute for Women's Health, University College London, London, UK aut Ådén Ulrika Department of Women's and Children's Health, Astrid Lindgren Children's Hospital, Karolinska Institutet, 17176, Stockholm, Sweden aut Olson Lars Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden aut Golay Xavier Institute of Neurology, University College London, London, UK aut Lagercrantz Hugo Department of Women's and Children's Health, Astrid Lindgren Children's Hospital, Karolinska Institutet, 17176, Stockholm, Sweden aut Robertson Nicola Institute for Women's Health, University College London, London, UK aut Galter Dagmar Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden aut Translational Stroke Research Springer-Verlag 4/2(2013-04-01), 248-257 1868-4483 4:2<248 2013 4 12975 https://doi.org/10.1007/s12975-012-0215-4 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s12975-012-0215-4 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Olson Linus Department of Women's and Children's Health, Astrid Lindgren Children's Hospital, Karolinska Institutet, 17176, Stockholm, Sweden aut NATIONALLICENCE 700 1- Faulkner Stuart Institute for Women's Health, University College London, London, UK aut NATIONALLICENCE 700 1- Lundströmer Karin Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden aut NATIONALLICENCE 700 1- Kerenyi Aron Institute for Women's Health, University College London, London, UK aut NATIONALLICENCE 700 1- Kelen Dorka Institute for Women's Health, University College London, London, UK aut NATIONALLICENCE 700 1- Chandrasekaran M. Institute for Women's Health, University College London, London, UK aut NATIONALLICENCE 700 1- Ådén Ulrika Department of Women's and Children's Health, Astrid Lindgren Children's Hospital, Karolinska Institutet, 17176, Stockholm, Sweden aut NATIONALLICENCE 700 1- Olson Lars Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden aut NATIONALLICENCE 700 1- Golay Xavier Institute of Neurology, University College London, London, UK aut NATIONALLICENCE 700 1- Lagercrantz Hugo Department of Women's and Children's Health, Astrid Lindgren Children's Hospital, Karolinska Institutet, 17176, Stockholm, Sweden aut NATIONALLICENCE 700 1- Robertson Nicola Institute for Women's Health, University College London, London, UK aut NATIONALLICENCE 700 1- Galter Dagmar Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden aut NATIONALLICENCE 773 0- Translational Stroke Research Springer-Verlag 4/2(2013-04-01), 248-257 1868-4483 4:2<248 2013 4 12975 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer