Article Text

RESUSCITATION WITH DIFFERENT OXYGEN CONCENTRATIONS GIVES A DOSE-DEPENDENT DECREASE IN BRAIN-DERIVED NEUROTROPHIC FACTOR EXPRESSION AND ACTIVITY IN NEWBORN PIG CEREBRAL CORTEX
  1. R Solberg1,
  2. J H Andresen1,
  3. M Wright1,
  4. O D Saugstad1
  1. 1Department of Paediatric Research, Rikshospitalet University Hospital, Oslo, Norway

Abstract

Objective Hypoxic-ischaemic injury of the brain in the neonatal period often leads to long-term neurological deficits. Brain-derived neurotrophic factor (BDNF) plays a crucial role in neuronal survival and maintenance, neurogenesis, learning and memory. Caspase-3, a specific apoptotic marker, plays a major role in cell death in immature neurons after brain injury, but can be blocked by BDNF.

Methods Global hypoxia was induced in newborn piglets following a standardised model; they were resuscitated with 21, 40 or 100% oxygen for 30 minutes and then observed for 9 h (n  =  11, 12, 10). RNA was isolated from snap-frozen brain tissue from the prefrontal cortex and gene expression levels for BDNF were determined by reverse transcription PCR. 100 mg brain tissue from the same area was used for immunoassay (ELISA).

Results Both reverse transcription PCR and the immunoassay showed a dose-dependent decrease in BDNF in the hyperoxic groups (p = 0.006 and p = 0.033 for 21 vs 100%, respectively). Caspase-3 correlated negatively with BDNF (r  =  −0.49, p = 0.024) and was significantly increased already by 40% (p = 0.032).

Conclusions Hyperoxia by resuscitation gives a dose-dependent decrease in BDNF, suggesting a lower neuroprotection, less caspase-3 inhibition and more neuronal apoptosis.

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