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Our aim was to use magnetic resonance spectroscopy (<jats:styled-content style=\"fixed-case\">MRS<\/jats:styled-content>) biomarkers and immunohistochemistry to investigate the cerebral effects of the <jats:styled-content style=\"fixed-case\">NHE<\/jats:styled-content> inhibitor, methyl isobutyl amiloride (<jats:styled-content style=\"fixed-case\">MIA<\/jats:styled-content>) given after severe perinatal asphyxia in the piglet. Eighteen male piglets (aged &lt;\u00a024\u00a0h) underwent transient global cerebral hypoxia\u2010ischaemia and were randomized to (i) saline placebo; or (ii) 3\u00a0mg\/kg intravenous <jats:styled-content style=\"fixed-case\">MIA<\/jats:styled-content> administered 10\u00a0min post\u2010insult and 8\u00a0hourly thereafter. Serial phosphorus\u201031 (<jats:sup>31<\/jats:sup>P) and proton (<jats:sup>1<\/jats:sup>H) <jats:styled-content style=\"fixed-case\">MRS<\/jats:styled-content> data were acquired before, during and up to 48\u00a0h after hypoxia\u2010ischaemia and metabolite\u2010ratio time\u2010series Area under the Curve (<jats:styled-content style=\"fixed-case\">AUC<\/jats:styled-content>) calculated. At 48\u00a0h, histological and immunohistochemical assessments quantified regional tissue injury. <jats:styled-content style=\"fixed-case\">MIA<\/jats:styled-content> decreased thalamic lactate\/N\u2010acetylaspartate and lactate\/creatine <jats:styled-content style=\"fixed-case\">AUC<\/jats:styled-content>s (both <jats:italic>p<\/jats:italic>\u00a0&lt;\u00a00.05) compared with placebo. Correlating with improved cerebral energy metabolism, transferase mediated biotinylated d\u2010UTP nick end\u2010labelling (<jats:styled-content style=\"fixed-case\">TUNEL<\/jats:styled-content>) positive cell density was reduced in the <jats:styled-content style=\"fixed-case\">MIA<\/jats:styled-content> group in cerebral cortex, thalamus and white matter (all <jats:italic>p<\/jats:italic>\u00a0&lt;\u00a00.05) and caspase 3 immunoreactive cells were reduced in pyriform cortex and caudate nucleus (both <jats:italic>p<\/jats:italic>\u00a0&lt;\u00a00.05). Microglial activation was reduced in pyriform and midtemporal cortex (both <jats:italic>p<\/jats:italic>\u00a0&lt;\u00a00.05). Treatment with <jats:styled-content style=\"fixed-case\">MIA<\/jats:styled-content> starting 10\u00a0min after hypoxia\u2010ischaemia was neuroprotective in this perinatal asphyxia model.<\/jats:p>","DOI":"10.1111\/jnc.12097","type":"journal-article","created":{"date-parts":[[2012,11,22]],"date-time":"2012-11-22T11:40:37Z","timestamp":1353584437000},"page":"645-657","source":"Crossref","is-referenced-by-count":23,"title":["Methyl\u2010isobutyl amiloride reduces brain Lac\/<scp>NAA<\/scp>, cell death and microglial activation in a perinatal asphyxia model"],"prefix":"10.1111","volume":"124","author":[{"given":"Nicola J.","family":"Robertson","sequence":"first","affiliation":[{"name":"Institute for Women's Health University College London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takenori","family":"Kato","sequence":"additional","affiliation":[{"name":"Institute for Women's Health University College London London UK"},{"name":"Nagoya City University Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan","family":"Bainbridge","sequence":"additional","affiliation":[{"name":"Medical Physics and Bioengineering University College London Hospitals London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manigandan","family":"Chandrasekaran","sequence":"additional","affiliation":[{"name":"Institute for Women's Health University College London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Osuke","family":"Iwata","sequence":"additional","affiliation":[{"name":"Institute for Women's Health University College London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Kapetanakis","sequence":"additional","affiliation":[{"name":"Institute for Women's Health University College London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stuart","family":"Faulkner","sequence":"additional","affiliation":[{"name":"Institute for Women's Health University College London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeanie","family":"Cheong","sequence":"additional","affiliation":[{"name":"Institute for Women's Health University College London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sachiko","family":"Iwata","sequence":"additional","affiliation":[{"name":"Institute for Women's Health University College London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariya","family":"Hristova","sequence":"additional","affiliation":[{"name":"Institute for Women's Health University College London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ernest","family":"Cady","sequence":"additional","affiliation":[{"name":"Medical Physics and Bioengineering University College London Hospitals London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gennadij","family":"Raivich","sequence":"additional","affiliation":[{"name":"Institute for Women's Health University College London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2012,12,26]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0735-1097(02)01693-5"},{"key":"e_1_2_9_3_1","doi-asserted-by":"crossref","unstructured":"AzzopardiD.(2011)Neuroprotective effects of hypothermia combined with inhaled xenon following perinatal asphyxia (TOBY Xe). 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