Journal
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
Volume 36, Issue 8, Pages 1396-1411Publisher
SAGE PUBLICATIONS INC
DOI: 10.1177/0271678X15608862
Keywords
Birth asphyxia; hypoxia-ischemia; neuroprotection; neonatal encephalopathy; remote ischemic postconditioning
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Funding
- MRC [MR/J00457X/1]
- Basque Government Postdoctoral Program [POS_2013_1_191]
- UK Department of Health's National Institute for Health Research Biomedical Research Centres funding scheme
- Medical Research Council [MR/J00457X/1] Funding Source: researchfish
- MRC [MR/J00457X/1] Funding Source: UKRI
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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.
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