The common antitussive agent dextromethorphan protects against hyperoxia-induced cell death in established in vivo and in vitro models of neonatal brain injury.
Preterm infants are prematurely subjected to relatively high oxygen concentrations, even when supplemental oxygen is not administered. There is increasing evidence to show that an excess of oxygen is toxic to the developing brain. Dextromethorphan (DM), a frequently used antitussive agent with pleiotropic mechanisms of action, has been shown to be neuroprotective in various models of central nervous system pathology. Due to its numerous beneficial properties, it might also be able to counteract detrimental effects of a neonatal oxygen insult. The aim of the current study was to evaluate its therapeutic potential in established cell culture and rodent models of hyperoxia-induced neonatal brain injury. For in vitro studies pre- and immature oligodendroglial (OLN-93) cells were subjected to hyperoxic conditions for 48 h after pre-treatment with increasing doses of DM. For in vivo studies 6-day-old Wistar rat pups received a single intraperitoneal injection of DM in two different dosages prior to being exposed to hyperoxia for 24h. Cell viability and caspase-3 activation were assessed as outcome parameters at the end of exposure. DM significantly increased cell viability in immature oligodendroglial cells subjected to hyperoxia. In pre-oligodendroglial cells cell viability was not significantly affected by DM treatment. In vivo caspase-3 activation induced by hyperoxic exposure was significantly lower after administration of DM in gray and white matter areas. In control animals kept under normoxic conditions DM did not significantly influence caspase-3-dependent apoptosis. The present results indicate that DM is a promising and safe treatment strategy for neonatal hyperoxia-induced brain injury that merits further investigation.
['Posod|A|A|', 'Pinzer|K|K|', 'Urbanek|M|M|', 'Wegleiter|K|K|', 'Keller|M|M|', 'Kiechl-Kohlendorfer|U|U|', 'Griesmaier|E|E|']
D000818:Animals D000831:Animals, Newborn D000996:Antitussive Agents D017209:Apoptosis D001921:Brain D001930:Brain Injuries D053148:Caspase 3 D002460:Cell Line D002470:Cell Survival D016207:Cytokines D003915:Dextromethorphan D004195:Disease Models, Animal D004305:Dose-Response Relationship, Drug D066128:Gray Matter D018496:Hyperoxia D018696:Neuroprotective Agents D009836:Oligodendroglia D010100:Oxygen D017208:Rats, Wistar D016194:Receptors, N-Methyl-D-Aspartate D017480:Receptors, sigma D066127:White Matter
dextromethorphan neonatal brain injury OLN-93 hyperoxia oxygen toxicity sigma receptor