• Osuke Iwata, Sachiko Iwata, John S Thornton, Enrico De Vita, Alan Bainbridge, Linda Herbert, Francesco Scaravilli, Donald Peebles, John S Wyatt, Ernest B Cady, and Nicola J Robertson.
• Centre for Perinatal Brain Research, Institute for Women's Health, University College London, and Lysholm Department of Neuroradiology, National Hospital for Neurology and Neurosurgery, London, UK. o.iwata... more @orbix.uk.net less
• Brain Res. 2007 Jun 18;1154:173-80.

ObjectiveFor optimal neuroprotection following transient perinatal hypoxia-ischaemia (HI), therapy should start before overt secondary energy failure and its irreversible neurotoxic cascade. Hypothermia is a promising neuroprotective intervention that also prolongs the therapeutic time window ("latent-phase"; the period between re-establishment of apparently normal cerebral metabolism after HI, and the start of secondary energy failure). The influences of HI severity on latent-phase duration and regional neuroprotection are unclear. Under normothermia and delayed whole-body cooling to 35 and 33 degrees C we aimed to assess relationships between HI severity and: (i) latent-phase duration; (ii) secondary-energy-failure severity; and (iii) neuronal injury 48 h following HI.MethodsNewborn piglets were randomized to: (i) HI-normothermia (n=12), (ii) HI-35 degrees C (n=7), and (iii) HI-33 degrees C (n=10). HI-35 degrees C and HI-33 degrees C piglets were cooled between 2 and 26 h after HI. Insult and secondary-energy-failure severity and latent-phase duration were evaluated using phosphorus magnetic resonance spectroscopy and compared with neuronal death in cortical-grey and deep-grey matter.ResultsMore severe HI was associated with shorter latent-phase (p=0.002), worse secondary energy failure (p=0.023) and more cortical-grey-matter neuronal death (p=0.016).ConclusionsLatent-phase duration is inversely related to insult severity; latent-phase brevity may explain the apparently less effective neuroprotection following severe cerebral HI.

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