Abstract
Background and aims: Hyperoxia is a high risk factor in the pathogenesis of preterm brain injury. Oxygen, at supraphysiological concentrations has been shown to cause an increase in free radical formation, inflammatory response and apoptotic cell death and subsequently contributes to brain injury. Dextromethorphan (DM) has been shown to be protective against inflammation-mediated, hypoxic-ischemic and excitotoxic brain injury. This study focuses on potential effects and underlying mechanisms of DM in a neonatal animal model of hyperoxic brain injury.
Methods: On postnatal day six (P6) rat pups were randomly injected intraperitoneally with i) DM 5μg/g body weight, (bw), ii) DM 25μg/g bw and iii) PBS as control. Subsequent to the injection rats were exposed to either normoxia (21% O2) or hyperoxia (>90% O2) for 24 hours. Endpoint was set at P7. Western Blot (WB) and immunohistochemistry analysed the effect of DM on apoptosis by activation of caspase-3 and on pro- and anti-inflammatory cytokines (interleukin (IL) 18 and 10).
Results: A single dose of DM (25μg/g bw) significantly reduced the number of caspase-3 positive cells after hyperoxia in temporoparietal, parietofrontal and retrosplenial cortex and in occipital and frontal white matter. Preliminary data indicate that IL-10 levels analysed by WB are decreased by hyperoxia and restored to normal levels by administration of DM. DM showed no effect on interleukin 18 expression.
Conclusion: This study shows a protective effect of DM against hyperoxia-induced apoptotic cell death and inflammatory responses in the newborn rat brain.
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Griesmaier, E., Kampkötter, C., Posod, A. et al. 109 Evaluation of Dextromethorphan as Neuroprotective Strategy in Neonatal Hyperoxic Brain Injury. Pediatr Res 68 (Suppl 1), 58 (2010). https://doi.org/10.1203/00006450-201011001-00109
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DOI: https://doi.org/10.1203/00006450-201011001-00109