Article Text

DEXTROMETHORPHAN PREVENTS HYPEROXIA-INDUCED CELL DEATH IN THE NEWBORN RAT BRAIN
  1. E Pircher1,
  2. E Griesmaier 1,
  3. M Tschirch 1,
  4. E Griesmaier 1,
  5. G Urbanek 1,
  6. M Simbruner 1,
  7. M Keller1
  1. 1Department of Pediatrics IV, Medical University Innsbruck, Innsbruck, Tirol, Austria

Abstract

Objective Preterm newborns are at high risk of neurological deficits related to perinatal brain damage. Evidence is increasing that, especially in the developing preterm brain, oxygen can constitute a neurotoxic factor and subsequently contribute to brain injury (Felderhoff et al, 2004). It has been shown that dextromethorphan, a low-affinity N-methyl-d-aspartate receptor antagonist with anti-inflammatory properties, is protective in in-vivo studies on preterm brain injury (McDonald et al, 1990; Keller et al, 2007). Whether dextromethorphan is also protective in hyperoxia-induced neonatal brain injury is not known.

Hypothesis We hypothesised that dextromethorphan prevents hyperoxia-induced brain damage in newborn rats.

Methods Wistar rats were randomly injected intraperitoneally with dextromethorphan (5 μg/g body weight) or PBS on postnatal day 2 and exposed to normoxia (21% oxygen) or hyperoxia (100% oxygen) for 48 h. Endpoints were set at postnatal day 4 and the number of activated caspase-3-positive cells analysed in 10 different brain regions (Ikonomidou et al, 2006).

Results Systemic hyperoxia significantly increased the number of activated caspase-3-positive cells in mediodorsal, laterodorsal and ventral thalamus. After one single dose of dextromethorphan this significant increase in hyperoxia-induced apoptosis could no longer be detected.

Conclusions Oxygen is widely used in neonatal intensive care. This study supplies evidence of oxygen being neurotoxic in the developing brain and the neuroprotective potential of dextromethorphan. Dextromethorphan might thus be a promising neuroprotective drug in neonatology. Further studies are mandatory.

Statistics from Altmetric.com

Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.