Contrary to adult, neonatal rats show pronounced brain uptake of corticosteroids

Neurotoxic adverse effects after systemic corticosteroid administration are elevated in preterm infants. To test whether this might be related to an immature blood-brain barrier (BBB) that permits corticosteroids to enter the brain and induce neurotoxic effects, this study assessed the differences in brain permeability of triamcinolone acetonide after intratracheal administration to neonatal (10- to 11-day-old) and adult rats. Triamcinolone acetonide (or the phosphate prodrug in the case of neonatal rats) was administered intratracheally to neonatal rats at doses of 2.5, 25, or 50 mu g/kg and to adult rats at 100 mu g/kg. An ex vivo receptor binding assay was used to monitor the cumulative brain and liver glucocorticoid receptor occupancies over 6 h. Brain and liver receptor occupancies in neonates were similar for the 25 and 50 mu g/kg triamcinolone acetonide phosphate (brain/liver receptor occupancy ratio, 1.10 +/- 0.14 and 0.87 +/- 0.13, respectively), whereas some reduction in the brain permeability was seen at the lower dose. After intratracheal administration of 100 mu g/kg triamcinolone acetonide to adult rats, receptor occupancies in the brain were significantly lower (brain/ liver ratio, 0.21 +/- 0.14; p < 0.001). The study demonstrated that glucocorticoids enter the brain of neonatal rats because of an immature BBB. The results of this study support the hypothesis that neurotoxic adverse effects in preterm infants after systemic corticosteroid administration might be related to an immature BBB.