Increased cerebral lactate during hypoxia may be neuroprotective in newborn piglets with intrauterine growth restriction

Moxon-Lester, Leith, Sinclair, Kate, Burke, Christopher, Cowin, Gary J., Rose, Stephen E. and Colditz, Paul (2007) Increased cerebral lactate during hypoxia may be neuroprotective in newborn piglets with intrauterine growth restriction. Brain Research, 1179 7: 79-88. doi:10.1016/j.brainres.2007.08.037


Author Moxon-Lester, Leith
Sinclair, Kate
Burke, Christopher
Cowin, Gary J.
Rose, Stephen E.
Colditz, Paul
Title Increased cerebral lactate during hypoxia may be neuroprotective in newborn piglets with intrauterine growth restriction
Journal name Brain Research   Check publisher's open access policy
ISSN 0006-8993
Publication date 2007-11-07
Sub-type Article (original research)
DOI 10.1016/j.brainres.2007.08.037
Volume 1179
Issue 7
Start page 79
End page 88
Total pages 10
Place of publication Amsterdam, Netherlands
Publisher Elsevier
Language eng
Subject 111403 Paediatrics
110903 Central Nervous System
Abstract Intrauterine growth restriction (IUGR) can increase susceptibility to perinatal hypoxic brain injury for reasons that are unknown. Previous studies of the neonatal IUGR brain have suggested that the cerebral mitochondrial capacity is reduced but the glycolytic capacity increased relative to normal weight (NW) neonates. In view of these two factors, we hypothesized that the generation of brain lactate during a mild hypoxic insult would be greater in neonatal IUGR piglets compared to NW piglets. Brain lactate/N-acetylaspartate (NAA) ratios and apparent diffusion coefficients (ADCs) were determined by proton magnetic resonance spectroscopy and imaging of the brain before, during and after hypoxia in seven neonatal piglets with asymmetric IUGR and six NW piglets. During hypoxia, IUGR piglets had significantly higher brain lactate/NAA ratios than NW piglets (P = 0.046). The lactate response in the IUGR piglets correlated inversely with apoptosis in the thalamus and frontal cortex of the brain measured 4 h post hypoxia (Pearson's r = 0.86, P < 0.05). Apoptosis in IUGR piglets with high brain lactate was similar to that in the NW piglets whereas IUGR piglets with low brain lactate had significantly higher apoptosis than NW piglets (P = 0.019). ADCs in the high lactate IUGR piglets were significantly lower during hypoxia than in all the other piglets. This signifies increased diffusion of water into brain cells during hypoxia, possibly in response to increased intracellular osmolality caused by high intracellular lactate concentrations. These findings support previous studies showing increased susceptibility to hypoxic brain injury in IUGR neonates but suggest that increased glycolysis during hypoxia confers neuroprotection in some IUGR piglets.
Keyword Intrauterine growth restriction
Hypoxia
Lactate
Neonate
Apoptosis
Apparent diffusion coefficient
Magnetic resonance spectroscopy
Q-Index Code CX

 
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