Remote ischemic postconditioning for neuroprotection after newborn hypoxia–ischemia: systematic review of preclinical studies

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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Short-term outcomes of remote ischemic postconditioning 1 h after perinatal hypoxia–ischemia in term piglets

Pediatric Research ◽

10.1038/s41390-020-0878-6 ◽

2020 ◽

Cited By ~ 1

Author(s):

Kasper J. Kyng ◽

Sigrid Kerrn-Jespersen ◽

Kristine Bennedsgaard ◽

Torjus Skajaa ◽

Michael Pedersen ◽

...

Keyword(s):

Ischemic Postconditioning ◽

Perinatal Hypoxia ◽

Short Term ◽

Remote Ischemic Postconditioning ◽

Hypoxia Ischemia

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Magnesium Is Not Consistently Neuroprotective for Perinatal Hypoxia-Ischemia in Term-Equivalent Models in Preclinical Studies: A Systematic Review

Developmental Neuroscience ◽

10.1159/000362206 ◽

2014 ◽

Vol 36 (2) ◽

pp. 73-82 ◽

Cited By ~ 40

Author(s):

Robert Galinsky ◽

Laura Bennet ◽

Floris Groenendaal ◽

Christopher A. Lear ◽

Sidhartha Tan ◽

...

Keyword(s):

Systematic Review ◽

Preclinical Studies ◽

Perinatal Hypoxia ◽

Equivalent Models ◽

Hypoxia Ischemia

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Immediate Remote Ischemic Postconditioning Reduces Brain Nitrotyrosine Formation in a Piglet Asphyxia Model

Oxidative Medicine and Cellular Longevity ◽

10.1155/2016/5763743 ◽

2016 ◽

Vol 2016 ◽

pp. 1-11 ◽

Cited By ~ 12

Author(s):

Eridan Rocha-Ferreira ◽

Brogan Rudge ◽

Michael P. Hughes ◽

Ahad A. Rahim ◽

Mariya Hristova ◽

...

Keyword(s):

Brain Injury ◽

Beneficial Effect ◽

Nitrosative Stress ◽

Birth Asphyxia ◽

Treated Group ◽

Ischemic Postconditioning ◽

Perinatal Hypoxia ◽

Enos Expression ◽

Remote Ischemic Postconditioning ◽

Hypoxia Ischemia

Remote ischemic postconditioning (RIPostC) is a promising therapeutic intervention that could be administered as an alternative to cooling in cases of perinatal hypoxia-ischemia (HI). In the current study we hypothesized that RIPostC in the piglet model of birth asphyxia confers protection by reducing nitrosative stress and subsequent nitrotyrosine formation, as well as having an effect on glial immunoreactivity. Postnatal day 1 (P1) piglets underwent HI brain injury and were randomised to HI (control) or HI + RIPostC. Immunohistochemistry assessment 48 hours after HI revealed a significant decrease in brain nitrotyrosine deposits in the RIPostC-treated group (p=0.02). This was accompanied by a significant increase in eNOS expression (p<0.0001) and decrease in iNOS (p=0.010), with no alteration in nNOS activity. Interestingly, RIPostC treatment was associated with a significant increase in GFAP (p=0.002) and IBA1 (p=0.006), markers of astroglial and microglial activity, respectively. The current study demonstrates a beneficial effect of RIPostC therapy in the preclinical piglet model of neonatal asphyxia, which appears to be mediated by modulation of nitrosative stress, despite glial activation.

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