DEXAMETHASONE PREVENTS APOPTOSIS IN A NEONATAL RAT MODEL OF HYPOXIC-ISCHEMIC ENCEPHALOPATHY (HIE) BY A REACTIVE OXYGEN SPECIES-INDEPENDENT MECHANISM

It has previously been shown, in a neonatal rat model of hypoxic-ische mic encephalopathy (HIE), that neuronal injury can be attenuated by pr etreatment with dexamethasone. The mechanism by which dexamethasone ex erts this protective effect is not known. Using the same neonatal rat model of HIE, we found pretreatment with dexamethasone to have no effe ct on the generation of superoxide radical, products of lipid peroxida tion, peroxynitrite-mediated tissue damage or bcl-2 protein expression . However, dexamethasone did inhibit the induction of c-fos transcript ion seen following HIE, and subsequent evidence of apoptosis. We concl ude that it is possible to Limit hypoxic-ischemic neuronal injury, des pite the continued production of reactive oxygen species, by intervent ions which block the cascade of events culminating in apoptosis. The i nvolvement of apoptosis in the neuronal injury of HIE, if confirmed in acutely asphyxiated human infants, suggests that there may be a post- injury 'window of opportunity' for neuroprotective interventions.