Increased plasma beta-hydroxybutyrate, preserved cerebral energy metabolism, and amelioration of brain damage during neonatal hypoxia ischemia with dexamethasone pretreatment

Dexamethasone (DEX) pretreatment has been shown to be neuroprotective in a neonatal rat model of hypoxia ischemia (HI). The exact mechanism of this ne uroprotection is still unknown. This study used P-31 nuclear magnetic reson ance spectroscopy to monitor energy metabolism during a 3-h episode of HI i n 7-d-old rat pups in one of two groups. The first group was pretreated wit h 0.1 mt saline (i.p.) and the second group was treated with 0.1 mt of 0.1m g/kg DEX (i.p.) 22 h before HI. Animals pretreated with DEX had elevated nu cleoside triphosphate and phosphocreatine levels during HI when compared wi th controls. Saline-treated animals had significant decreases in nucleoside triphosphate and phosphocreatine and increases in inorganic phosphate over this same period. P-31 nuclear magnetic resonance data unequivocally demon strate preservation of energy metabolism during HI in neonatal rats pretrea ted with DEX. Animals pretreated with DEX had little or no brain damage fol lowing 3 h of HI when compared with matched controls, which experienced sev ere neuronal loss and cortical infarction, These same pretreated animals ha d an increase in blood beta-hydroxybutyrate levels before ischemia, suggest ing an increase in ketone bodies, which is the neonate's primary energy sou rce. Elevation of ketone bodies appears to be one of the mechanisms by whic h DEX pretreatment provides neuroprotection during HI in the neonatal rat.