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A Piglet Model of Neonatal Hypoxic-Ischemic Encephalopathy
Published on: May 16, 2015
Increased cerebral lactate during hypoxia may be neuroprotective in newborn piglets with intrauterine growth
Leith Moxon-Lester1, Kate Sinclair, Christopher Burke
1Perinatal Research Centre, University of Queensland, Royal Brisbane and Women's Hospital, Level 6 Ned Hanlon Building, Brisbane, Australia. l.lester@uq.edu.au
Insights
Intrauterine growth restriction (IUGR) increases susceptibility to perinatal hypoxic brain injury. In IUGR piglets, higher brain lactate during hypoxia correlated with less brain cell death, suggesting glycolysis may offer neuroprotection.
Area of Science:
- Neuroscience
- Perinatal Medicine
- Biochemistry
Background:
- Intrauterine growth restriction (IUGR) is linked to increased risk of perinatal hypoxic brain injury.
- Neonatal IUGR brains may have reduced mitochondrial and increased glycolytic capacity.
- The precise mechanisms underlying IUGR's impact on hypoxic brain injury remain unclear.
Purpose of the Study:
- To investigate the hypothesis that neonatal IUGR piglets generate more brain lactate during hypoxia compared to normal weight (NW) piglets.
- To explore the relationship between brain lactate levels, apoptosis, and water diffusion in IUGR piglets during hypoxic insults.
Main Methods:
- Utilized proton magnetic resonance spectroscopy and imaging to measure brain lactate/N-acetylaspartate (NAA) ratios and apparent diffusion coefficients (ADCs).
- Studied seven neonatal IUGR piglets and six NW piglets before, during, and after a mild hypoxic insult.
- Quantified apoptosis in specific brain regions 4 hours post-hypoxia.
Main Results:
- IUGR piglets exhibited significantly higher brain lactate/NAA ratios during hypoxia compared to NW piglets (P=0.046).
- Elevated brain lactate in IUGR piglets inversely correlated with thalamic and frontal cortex apoptosis (Pearson's r=0.86, P<0.05).
- Lower ADCs in high-lactate IUGR piglets indicated increased intracellular water diffusion, potentially due to high lactate concentrations.
Conclusions:
- Findings support increased susceptibility to hypoxic brain injury in IUGR neonates.
- Increased glycolysis during hypoxia may confer a neuroprotective effect in some IUGR piglets.
- Elevated brain lactate during hypoxia could be a marker for altered brain metabolism and water movement in IUGR.
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.
