At the same severe elevations in blood phenylalaline (Phe) levels maintained for 4 h, much higher cerebral Phe concentrations were found in 4-day-old than in 16- or 70-day-old rats. In order to compare this developmental change with ¹⁴C-Phe influx mediated by the L transport system, the rapid intracarotid injection method was adapted for use in neonatal rats. The brain uptake index (BUI) thus determined for the first time through the suckling period was significantly higher on the 4th day of age than on the 7th or 24th day, while no significant change occurred during subsequent life. This early period of change in influx across the blood-brain barrier overlapped with the age period of decrease of the hyperphenylalaninemia-associated accumulation of Phe in the brain. The results indicate that by the time when intermittent feeding begins, the brain has developed a considerable ability (a) to protect itself against physiological (e.g. postprandial) fluctuations in circulating Phe levels, and (b) to restrict the cerebral accumulation of Phe from pathologically elevated blood concentrations such as those in phenylketonuria.

No abstract