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

13 Scopus citations


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 K ATP 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 (US)
Pages (from-to)1396-1411
Number of pages16
JournalJournal of Cerebral Blood Flow and Metabolism
Issue number8
StatePublished - Aug 1 2016


  • Birth asphyxia
  • hypoxia-ischemia
  • neonatal encephalopathy
  • neuroprotection
  • remote ischemic postconditioning

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine


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