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Brain Res. 2007 Jun 18;1154:173-80. Epub 2007 Apr 1.

"Therapeutic time window" duration decreases with increasing severity of cerebral hypoxia-ischaemia under normothermia and delayed hypothermia in newborn piglets.

Author information

  • 1Centre 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@orbix.uk.net

Abstract

OBJECTIVE:

For 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.

METHODS:

Newborn 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.

RESULTS:

More 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).

CONCLUSIONS:

Latent-phase duration is inversely related to insult severity; latent-phase brevity may explain the apparently less effective neuroprotection following severe cerebral HI.

PMID:
17475224
[PubMed - indexed for MEDLINE]
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