title: Immediate Remote Ischemic Postconditioning Reduces Brain Nitrotyrosine Formation in a Piglet Asphyxia Model.
abstract: 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.
authors.affiliation: Preclinical Neonatal Neuroprotection Group, UCL EGA Institute for Women's Health, London WC1E 6BT, UK.
authors.forename: Eridan
authors.initials: E
authors.lastname: Rocha-Ferreira
authors.affiliation: Preclinical Neonatal Neuroprotection Group, UCL EGA Institute for Women's Health, London WC1E 6BT, UK.
authors.forename: Brogan
authors.initials: B
authors.lastname: Rudge
authors.affiliation: Department of Pharmacology, UCL School of Pharmacy, London WC1N 1AX, UK.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Hughes
authors.affiliation: Department of Pharmacology, UCL School of Pharmacy, London WC1N 1AX, UK.
authors.forename: Ahad A
authors.initials: AA
authors.lastname: Rahim
authors.affiliation: Perinatal Brain Group, UCL EGA Institute for Women's Health, London WC1E 6HX, UK.
authors.forename: Mariya
authors.initials: M
authors.lastname: Hristova
authors.affiliation: Preclinical Neonatal Neuroprotection Group, UCL EGA Institute for Women's Health, London WC1E 6BT, UK.
authors.forename: Nicola J
authors.initials: NJ
authors.lastname: Robertson
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001237:Asphyxia / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D057775:Ischemic Postconditioning; D009457:Neuroglia / Q000378:metabolism / Q000473:pathology; D019001:Nitric Oxide Synthase / Q000378:metabolism; D018384:Oxidative Stress; D034421:Sus scrofa; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000378:metabolism
chemical_list: D015415:Biomarkers; C002744:3-nitrotyrosine; D014443:Tyrosine; D019001:Nitric Oxide Synthase