title: Immediate remote ischemic postconditioning after hypoxia ischemia in piglets protects cerebral white matter but not grey matter.
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.
authors.affiliation: Institute for Women's Health, University College London, London, UK.
authors.forename: Mojgan
authors.initials: M
authors.lastname: Ezzati
authors.affiliation: Physics and Bioengineering, University College London NHS Trust, London, UK.
authors.forename: Alan
authors.initials: A
authors.lastname: Bainbridge
authors.affiliation: Institute for Women's Health, University College London, London, UK.
authors.forename: Kevin D
authors.initials: KD
authors.lastname: Broad
authors.affiliation: Institute for Women's Health, University College London, London, UK.
authors.forename: Go
authors.initials: G
authors.lastname: Kawano
authors.affiliation: Institute for Women's Health, University College London, London, UK.
authors.forename: Aaron
authors.initials: A
authors.lastname: Oliver-Taylor
authors.affiliation: Institute for Women's Health, University College London, London, UK.
authors.forename: Eridan
authors.initials: E
authors.lastname: Rocha-Ferreira
authors.affiliation: Institute for Women's Health, University College London, London, UK.
authors.forename: Daniel
authors.initials: D
authors.lastname: Alonso-Alconada
authors.affiliation: Institute for Women's Health, University College London, London, UK.
authors.forename: Igor
authors.initials: I
authors.lastname: Fierens
authors.affiliation: Institute for Women's Health, University College London, London, UK.
authors.forename: Jamshid
authors.initials: J
authors.lastname: Rostami
authors.affiliation: Institute for Women's Health, University College London, London, UK.
authors.forename: K
authors.initials: K
authors.lastname: Jane Hassell
authors.affiliation: Medical Physics and Biomedical Engineering, University College London, London, UK.
authors.forename: Ilias
authors.initials: I
authors.lastname: Tachtsidis
authors.affiliation: Department of Perinatal Imaging and Health, Division of Imaging Sciences and Biomedical Engineering, King's College London, King's Health Partners, St. Thomas' Hospital, London, UK Inserm, U1141, Paris, France University Paris Diderot, Sorbonne Paris Cité, Paris, France PremUP, Paris, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Gressens
authors.affiliation: Institute for Women's Health, University College London, London, UK.
authors.forename: Mariya
authors.initials: M
authors.lastname: Hristova
authors.affiliation: Institute for Women's Health, University College London, London, UK.
authors.forename: Kate
authors.initials: K
authors.lastname: Bennett
authors.affiliation: PremUP, Paris, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Lebon
authors.affiliation: Department of Perinatal Imaging and Health, Division of Imaging Sciences and Biomedical Engineering, King's College London, King's Health Partners, St. Thomas' Hospital, London, UK Inserm, U1141, Paris, France University Paris Diderot, Sorbonne Paris Cité, Paris, France PremUP, Paris, France.
authors.forename: Bobbi
authors.initials: B
authors.lastname: Fleiss
authors.affiliation: The Hatter Cardiovascular Institute, University College London, London, UK.
authors.forename: Derek
authors.initials: D
authors.lastname: Yellon
authors.affiliation: The Hatter Cardiovascular Institute, University College London, London, UK Cardiovascular and Metabolic Disorders Program, Duke-NUS Graduate Medical School, Singapore, Singapore National Heart Centre Singapore, Singapore.
authors.forename: Derek J
authors.initials: DJ
authors.lastname: Hausenloy
authors.affiliation: Institute of Neurology, University College London, London, UK.
authors.forename: Xavier
authors.initials: X
authors.lastname: Golay
authors.affiliation: Institute for Women's Health, University College London, London, UK n.robertson@ucl.ac.uk.
authors.forename: Nicola J
authors.initials: NJ
authors.lastname: Robertson
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D001931:Brain Mapping; D004195:Disease Models, Animal; D004569:Electroencephalography; D015870:Gene Expression; D066128:Gray Matter / Q000098:blood supply / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology*; D020925:Hypoxia-Ischemia, Brain / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D007150:Immunohistochemistry; D057775:Ischemic Postconditioning / Q000379:methods*; D054086:KATP Channels / Q000235:genetics; D019344:Lactic Acid / Q000378:metabolism; D035002:Lower Extremity / Q000098:blood supply*; D009682:Magnetic Resonance Spectroscopy; D044022:Receptor, Endothelin A / Q000235:genetics; D013552:Swine; D066127:White Matter / Q000098:blood supply / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology*
chemical_list: D015415:Biomarkers; D054086:KATP Channels; D044022:Receptor, Endothelin A; D001224:Aspartic Acid; D019344:Lactic Acid; D000255:Adenosine Triphosphate; C000179:N-acetylaspartate
keywords: Birth asphyxia; hypoxia–ischemia; neonatal encephalopathy; neuroprotection; remote ischemic postconditioning