Comparison of Three Hypothermic Target Temperatures for the Treatment of Hypoxic Ischemia

MRNA Level Responses of Eight Genes in the Piglet Brain

Linus Olson, Stuart Faulkner, Karin Lundströmer, Aron Kerenyi, Dorka Kelen, M. Chandrasekaran, Ulrika Ådén, Lars Olson, Xavier Golay, Hugo Lagercrantz, Nicola J. Robertson, Dagmar Galter

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)248-257
Number of pages10
JournalTranslational Stroke Research
Volume4
Issue number2
DOIs
StatePublished - 2013
Externally publishedYes

Fingerprint

Ischemia
Messenger RNA
Temperature
Brain
Genes
Down-Regulation
Therapeutics
Brain-Derived Neurotrophic Factor
Hypothermia
Brain Ischemia
Body Temperature
Cerebral Cortex
Hippocampus
Newborn Infant

Keywords

  • Hypoxic ischemic encephalopathy
  • In situ hybridisation
  • Neonatal asphyxia
  • Neuronal and glial markers
  • Piglets
  • Therapeutic hypothermia

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)
  • Cardiology and Cardiovascular Medicine

Cite this

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

In: Translational Stroke Research, Vol. 4, No. 2, 2013, p. 248-257.

Research output: Contribution to journalArticle

Olson, L, Faulkner, S, Lundströmer, K, Kerenyi, A, Kelen, D, Chandrasekaran, M, Ådén, U, Olson, L, Golay, X, Lagercrantz, H, Robertson, NJ & Galter, D 2013, 'Comparison of Three Hypothermic Target Temperatures for the Treatment of Hypoxic Ischemia: MRNA Level Responses of Eight Genes in the Piglet Brain', Translational Stroke Research, vol. 4, no. 2, pp. 248-257. https://doi.org/10.1007/s12975-012-0215-4
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. / Comparison of Three Hypothermic Target Temperatures for the Treatment of Hypoxic Ischemia : MRNA Level Responses of Eight Genes in the Piglet Brain. In: Translational Stroke Research. 2013 ; Vol. 4, No. 2. pp. 248-257.
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abstract = "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.",
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