Immediate remote ischemic postconditioning after hypoxia ischemia in piglets protects cerebral white matter but not grey matter

Mojgan Ezzati, Alan Bainbridge, Kevin D Broad, Go Kawano, Aaron Oliver-Taylor, Eridan Rocha-Ferreira, Daniel Alonso-Alconada, Igor Fierens, Jamshid Rostami, K Jane Hassell, Ilias Tachtsidis, Pierre Gressens, Mariya Hristova, Kate Bennett, Sophie Lebon, Bobbi Fleiss, Derek Yellon, Derek J Hausenloy, Xavier Golay, Nicola J Robertson

Research output: Contribution to journalArticlepeer-review

Abstract

Remote ischemic postconditioning (RIPostC) is a promising therapeutic intervention whereby brief episodes of ischemia/reperfusion of one organ (limb) mitigate damage in another organ (brain) that has experienced severe hypoxia-ischemia. Our aim was to assess whether RIPostC is protective following cerebral hypoxia-ischemia in a piglet model of neonatal encephalopathy (NE) using magnetic resonance spectroscopy (MRS) biomarkers and immunohistochemistry. After hypoxia-ischemia (HI), 16 Large White female newborn piglets were randomized to: (i) no intervention (n = 8); (ii) RIPostC - with four, 10-min cycles of bilateral lower limb ischemia/reperfusion immediately after HI (n = 8). RIPostC reduced the hypoxic-ischemic-induced increase in white matter proton MRS lactate/N acetyl aspartate (p = 0.005) and increased whole brain phosphorus-31 MRS ATP (p = 0.039) over the 48 h after HI. Cell death was reduced with RIPostC in the periventricular white matter (p = 0.03), internal capsule (p = 0.002) and corpus callosum (p = 0.021); there was reduced microglial activation in corpus callosum (p = 0.001) and more surviving oligodendrocytes in corpus callosum (p = 0.029) and periventricular white matter (p = 0.001). Changes in gene expression were detected in the white matter at 48 h, including KATP channel and endothelin A receptor. Immediate RIPostC is a potentially safe and promising brain protective therapy for babies with NE with protection in white but not grey matter.

Original languageEnglish
Pages (from-to)1396-411
Number of pages16
JournalJournal of Cerebral Blood Flow and Metabolism
Volume36
Issue number8
DOIs
Publication statusPublished - Aug 2016

Keywords

  • Adenosine Triphosphate/metabolism
  • Animals
  • Animals, Newborn
  • Aspartic Acid/analogs & derivatives
  • Biomarkers/metabolism
  • Brain Mapping
  • Disease Models, Animal
  • Electroencephalography
  • Gene Expression
  • Gray Matter/blood supply
  • Hypoxia-Ischemia, Brain/diagnostic imaging
  • Immunohistochemistry
  • Ischemic Postconditioning/methods
  • KATP Channels/genetics
  • Lactic Acid/metabolism
  • Lower Extremity/blood supply
  • Magnetic Resonance Spectroscopy
  • Receptor, Endothelin A/genetics
  • Swine
  • White Matter/blood supply

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